SAJDVD Volume 8, Issue 4

THE SOUTH AFRICAN JOURNAL OF

DiabetesVascular Disease

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INSULIN RESISTANCE

OBESITY

HYPERTENSIONDYSLIPIDAEMIA

THROMBOSISATHEROSCLEROSIS

HYPERGLYCAEMIA

HYPERINSULINAEMIA

DIABETES &

VASCULAR DISEASE

Featured in this issue

UN call for action on NCDs

Outcomes of lifestyle-modification programmes

Diabetes patients under-treated for hypercholesterolaemia

New guidelines recommend lower LDL target

South African legislation on trans fatty acids

Oral health in diabetes

References: 1. Zander M, et al. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and ß-cell function in type 2 diabetes: a parallel-group study. Lancet. 2002;359:824-830. 2. Toft-Nielsen M-B, et al. Determinants of the Impaired Secretion of Glucagon-Like Peptide-1 in Type 2 Diabetic Patients. J Clin Endocrinol Metab. 2001;86(8):3717-3723. 3. Kjems LL, et al. The Influence of GLP-1 on Glucose-Stimulated Insulin Secretion. Effects on ß-Cell Sensitivity in Type 2 and Nondiabetic Subjects. Diabetes. 2003;52:380-386.

Novo Nordisk (Pty) Ltd. Reg. No.: 1959/000833/07. PO Box 783155, Sandton, 2146. Tel: (011) 202 0500 Fax: (011) 807 7989 www.novonordisk.co.za NN/DUO/4244/09/10/VER1

Diabetes | A whole new perspective

Are you looking at every part of diabetes?You might be missing GLP-1. It’s a natural hormone that helps regulate glucose metabolism. It also slows gastric emptying, promotes satiety, and plays a significant role in beta-cell function.1 Its multiple actions throughout the body are critical in diabetes.

Unfortunately, your patients might be missing GLP-1, too. Many people with type 2 diabetes may have impaired GLP-1 secretion and impaired beta-cell response to GLP-1.2,3 This could contribute to the pathogenesis of the disease.1

Looking at the whole problem is the most important part of understanding it. That’s why Novo Nordisk is dedicated to ongoing research and development in the management of diabetes.

HYPERINSULINAEMIA

ISSN 1811-6515

THE SOUTH AFRICAN JOURNAL OF

Diabetes & Vascular Disease

Corresponding EditorDr L LombarDNetcare, Kuilsrivier Hospital, Cape Town

Dr F maHomEDDepartment of Endocrinology, Grey’s Hospital, Pietermaritzburg

Consulting EditorsProF J-C mbaNYaProF aJ brINK

National Editorial BoardDr a amoDCentre for Diabetes, Endocrinology and metabolic Diseases, Life Healthcare, Chatsmed Gardens Hospital, Durban

Sr K bECKErTDiabetes Nurse, Paarl

ProF F boNNICIEmeritus Professor, Faculty of Health Sciences, University of Cape Town and President of Diabetes South africa

ProF r DELPorTDepartment of Family medicine,University of Pretoria

Dr L DISTILLErDirector of the Centre of Diabetes and Endocrinology, Houghton, Johannesburg

ProF WF moLLENTZEHead of Department of Internal medicine, University of the Free State, bloemfontein

ProF CD PoTGIETErSpecialist Nephrologist, University of Pretoria and Jakaranda Hospital, Pretoria

ProF K SLIWaassociate Professor of medicine and Cardiology, baragwanath Hospital, University of the Witwatersrand, Johan-nesburg

ProF YK SEEDaTEmeritus Professor of medicine and Honorary research associate, University of Natal, Durban

International Editorial BoardProF IW CamPbELLPhysician, Victoria Hospital, Kircaldy, Scotland, UK

ProF PJ GraNTProfessor of medicine and head of academic Unit of molecular Vascular medicine, Faculty of medicine and Health, University of Leeds; honorary consultant physician, United Leeds Teaching Hospitals NHS Trust, UK

ProF J-C mbaNYaProfessor of Endocrinology, Faculty of medicine and biomedical Sciences, University of Yaounde I, Cameroon and President, International Diabetes Federation

ProF N PoULTErProfessor of Preventive Cardiovascular medicine, Imperial College, School of medicine, London, UK

Dr H PUrCELLSenior research Fellow in Cardiology, royal brompton National Heart and Lung Hospital, London, UK

VOLUME 8 NUMBER 4 • NOVEMBER 2011www.diabetesjournal.co.za

CONTENTS Editorial

147 UN call for action: prevention and control of non-communicable diseasesL Lombard

Achieving Best Practice

149 Considering the patient perspective for assessing the outcomes of diabetes lifestyle modification programmes: what should we measure, and how?CD Barbosa, B Arnould, JB Gruenberger, PEH Schwarz

Reports

155 South African patients with diabetes are under-treated for hypercholesterolaemia: Survey of in-treatment hypercholesterolaemia highlights the need for intensified treatment in diabetesJ Aalbers

157 New guidelines recommend lower LDL target in high-risk cardiovascular patientsP Wagenaar

Nutrition Focus

159 Avoid these fats: Introduction to South African legislation on trans fatty acids

Case Studies

161 Type 2 diabetes patient without CVD, not achieving lipid targetsM Kirby

163 Type 2 diabetes patient with muscle aches on statin therapyP Twomey

References: 1. Zander M, et al. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and ß-cell function in type 2 diabetes: a parallel-group study. Lancet. 2002;359:824-830. 2. Toft-Nielsen M-B, et al. Determinants of the Impaired Secretion of Glucagon-Like Peptide-1 in Type 2 Diabetic Patients. J Clin Endocrinol Metab. 2001;86(8):3717-3723. 3. Kjems LL, et al. The Influence of GLP-1 on Glucose-Stimulated Insulin Secretion. Effects on ß-Cell Sensitivity in Type 2 and Nondiabetic Subjects. Diabetes. 2003;52:380-386.

Novo Nordisk (Pty) Ltd. Reg. No.: 1959/000833/07. PO Box 783155, Sandton, 2146. Tel: (011) 202 0500 Fax: (011) 807 7989 www.novonordisk.co.za NN/DUO/4244/09/10/VER1

Diabetes | A whole new perspective

Are you looking at every part of diabetes?You might be missing GLP-1. It’s a natural hormone that helps regulate glucose metabolism. It also slows gastric emptying, promotes satiety, and plays a significant role in beta-cell function.1 Its multiple actions throughout the body are critical in diabetes.

Unfortunately, your patients might be missing GLP-1, too. Many people with type 2 diabetes may have impaired GLP-1 secretion and impaired beta-cell response to GLP-1.2,3 This could contribute to the pathogenesis of the disease.1

Looking at the whole problem is the most important part of understanding it. That’s why Novo Nordisk is dedicated to ongoing research and development in the management of diabetes.

Assistant Editor: Special AssignmentsJULIa aaLbErSTEL: (021) 976-4378FAX: 086 610 3395e-mail: [email protected]

Development Editor: GLENDa HarDYCELL: 071 819 6425FAX: 086 610 3395e-mail: [email protected]

Production EditorSHaUNa GErmISHUIZENTEL: (021) 785-7178FAX: 086 628 1197e-mail: [email protected]

Editorial Assistant and CirculationELSabÉ bUrmEISTErTEL/FAX: (021) 976-8129e-mail: [email protected]

Production Co-ordinatorWENDY WEGENErTEL: (021) 976-4378e-mail: [email protected]

The South African Journal of Diabetes and Vascular Disease is published four times a year for Clinics-Cardive Publishing Co. and printed by Tandym Print. Articles in this Journal are sourced as per agreement with the British Journal of Diabetes and Vascular Disease

all correspondence to be directed to:

THE EDITorPO BOX 1013DUrbaNVILLE7551or [email protected]

TEL/FAX: (021) 976-8129INT: 2721 976-8129

The opinions, data and statements that appear in any articles published in this journal are those of the contributors. The publisher, editors and members of the editorial board do not necessarily share the views expressed herein. although every effort is made to ensure accuracy and avoid mistakes, no liability on the part of the publisher, editors, the editorial board or their agents or employees is accepted for the consequences of any inaccurate or misleading information.

Patient Leaflet

165 Taking control of your cholesterol levels

Diabetes Educator’s Focus

167 Oral health in diabetesG Hardy

Diabetes Personality

169 ‘Walking the walk’ to a greater understanding of diabetes

Journal Update

171 Southern African contributionsG Hardy

Report

175 Controversies at ESC 2011: Dietary approaches for lipid assessment

EASD Watch

178 2011 Update from Lisbon, Portugal

Diabetes News

186 New stem cell cryopreservation laboratory in Cape Town

187 Getting together: a diabetes camp in Stellenbosch

188 Celebrating World Diabetes Day

SA JOURNAL OF DIABETES & VASCULAR DISEASE EDITORIAL

VOLUME 8 NUMBER 4 • NOVEMBER 2011 147

Correspondence to: Dr Landi LombardNetcare Kuilsrivier Hospital, Cape TownTel: +27 0(21) 900-6350e-mail: [email protected]

S Afr J Diabetes Vasc Dis 2011; 8: 147–148

UN call for action: prevention and control of non-communicable diseasesLANDI LOMBARD

Landi Lombard

Worldwide, non-communicable diseases (NCDs) are currently responsible for more deaths than all other causes combined. Traditionally, high-income populations

have borne the burden of NCDs. However, current evidence indicates that the spread of disease is associated with increasing levels of economic development. Low- and middle-income countries now bear a greater burden of NCDs than high-income countries. In Africa, NCDs are projected by 2020 to cause almost three-quarters as many deaths as communicable, maternal–perinatal and nutritional diseases combined. Currently, over 80% of cardiovascular- and diabetes-related deaths occur in low- and middle-income countries.

NCDs worsen poverty, while poverty results in rising rates of such diseases. Strong evidence links poverty, lack of education and other social inequities to NCDs and their risk factors. Lower levels of education and residence in urban areas are associated with an increased risk of diabetes. Physical inactivity, daily smoking and regular alcohol consumption are more prevalent in those with the least education. Female blue-collar workers have the highest incidence of the metabolic syndrome, as well as higher rates of obesity. NCDs create serious socio-economic consequences by increasing individual and household impoverishment.

Paying for care associated with diabetes can cost low-income households up to a third of their incomes. Catastrophic hospitalisation expenditures are higher with NCDs compared with communicable diseases. In developing countries, the lack of healthcare capacity and dearth of social protection systems means that people with NCDs are more likely to become sick and die at a younger age.

At present, the main focus of healthcare for NCDs in many developing countries is hospital centred. In the case of cardiovascular diseases and diabetes, a large proportion of people at high risk remain undiagnosed. When a diagnosis is made, it is often at a late stage of the disease, when the patient is symptomatic and admitted to hospital with acute events or long-term complications and disabilities. Treatment for advanced-stage disease is expensive as high-technology interventions are required. The impact of NCDs can be prevented through primary healthcare measures to treat those who have contracted or are at high risk of contracting such diseases.

This issue of the journal focuses on three areas where primary care can make a difference – obesity, lipid management and food choices.

Cholesterol management in South AfricaThe CEPHEUS study on cholesterol management in diabetes high-lights the contribution that primary care can make to reducing car-diovascular events in patients with diabetes. The strength of this study is that it is representative of the public and private sectors, and the diverse communities of South Africa.

Primary-care practitioners, after evaluating the effect of the initial lipid-lowering agents prescribed, should up-titrate statins sensibily and use combination therapy in their diabetic patients. The CEPHEUS study confirms what has already been shown in other countries in the world, that healthcare professionals do not treat lipid levels effectively enough and therefore patients are still exposed to higher-than-necessary risk of cardiovascular disease. Healthcare professionals should know the targets and try harder to achieve these set targets in order to save lives.

New lipid guidelinesThis issue reports on the new South African lipid guidelines announced recently by the South African Heart Association and the Lipid and Atherosclerosis Society of Southern Africa (LASSA). The new guidelines are more complicated than the previous ones and use a three-tier design based on the Framingham risk score. The first tier of patients (target LDL < 1.8 mmol/l), who should be treated the most intensively, includes a wide variety of patients. This will put more pressure on medical aids for funding, especially combination therapy, but could also potentially save lives. Patients at this level of risk should probably be managed by specialists.

Legislation on trans fatty acids in foodThe worldwide prevalence of obesity has nearly doubled between 1980 and 2008. Growing globalisation and industrialisation is lead-

EDITORIAL SA JOURNAL OF DIABETES & VASCULAR DISEASE

ing to increased consumption of processed food, resulting in an upsurge of saturated fat, trans fats, salt and refined sugars in the diet.

In an article on new legislation regarding trans fatty acids in food, we read that Government is regulating this by law. The Department of Health is to be congratulated on this legislation which tries to protect the consumer against unsafe foods. The average South African consumer does not read labels or is unsure of what they mean and how to interpret them. Even healthcare professionals often do not know the recommended intake of the different fats. Removal of these unsafe products in foods should therefore be strongly supported.

In this issue, we also provide data from the Nutritional Information Centre, University of Stellenbosch (NICUS), which has responded to the new regulations on trans fatty acids with valuable advice for both health educators and patients.

Intervention StrategiesCo-ordinated multisectorial partnerships are required to sustainably prevent and manage NCDs. Government needs to prioritise preven-tion and control strategies and revitalise primary healthcare. The fact that many NCDs are long-term diseases demands a compre-

hensive healthcare system response that brings together a trained workforce with appropriate skills, affordable technologies, reliable supplies of medicines, referral systems and the empowerment of people for self care, all over a sustained period of time. Sustained primary healthcare measures encompassing essential interventions, palliative and long-term care are required. Preventive and health-care interventions relating to such diseases should be integrated into reproductive, maternal and child health programmes, espe-cially at the primary healthcare level.

The private sector should promote healthy behaviour and improve affordability and accessibility to healthy lifestyle choices. Initiatives by the food industry in reformulation of healthier products and in exercising responsible marketing are crucial. Suggested population-wide interventions include promoting public awareness on diet and physical activity. Civil society should support community awareness campaigns.

The knowledge and technology to fight the onset and effects on NCDs, particularly type 2 diabetes, already exists. It’s time for action; the moral, social and economic imperative is clear.

Source: Report of the Secretary-General, United Nations General Assembly, sixty-sixth session. Item 119 of preliminary list. Prevention and control of non-communicable diseases.

Important dates:• Abstract submissions by: 15 November 2011• Early Bird Registration closes: 30 November 2011

Enquiries:SIOP Congress O�ceTelephone: + 27 (0) 11 447 3876Email: [email protected]

F I N A L A N N O U N C E M E N T

Invited International Faculty Professor William L. Carroll (USA)

Dr Scott Howard (USA)

Dr Mhamed Harif (Morocco)

Professor Rolf Dieter Kortmann (Germany)

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Celebrating African Excellence Celebration de l’excellence Africaine

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21–23 March Woodstock • Cape Town, South Africa

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Parents, Professionals & Nurses


SA JOURNAL OF DIABETES & VASCULAR DISEASE ACHIEVING BEST PRACTICE

Considering the patient perspective for assessing the outcomes of diabetes lifestyle-modification programmes: what should we measure, and how?CARLA DIAS BARBOSA, BENOIT ARNOULD, JEAN BERNARD GRUENBERGER, PETER EH SCHWARZ

Abstract

Current evidence shows that type 2 diabetes can be effectively prevented and delayed by lifestyle modifi-cation. After careful development and pilot testing, a

rigorous evaluation of such programmes is crucial to assess their effectiveness prior to large-scale implementation. Inte-grating the patient perspective in this evaluation is essential. In principle, patient-reported outcomes (PRO) questionnaires can address this key question. However, researchers and clinicians lack a clear framework to make a sound selection of appropriate measures among the large set of possible questionnaires. As a consequence, it is unclear what is the most useful information to be captured from patients when assessing a new programme, so that it can be determined whether the programme can be generalised to a larger population: is it health-related quality of life, satisfaction or something different which could predict the long-term suc-cess of the programme? We recommend a specific approach, better adapted to the nature of the intervention, and sug-gest a selection of a few existing PRO measures that could satisfy the requirements.

Keywords: diabetes education, lifestyle modification, measure-ment instruments, patient-reported outcomes, type 2 diabetes

IntroductionType 2 diabetes has reached epidemic proportions throughout the world. In 2010, approximately 285 million people worldwide had diabetes; this number is projected to increase to 438 million by 2030.1 Major prevention studies have shown that diabetes can be effectively delayed or prevented in individuals with impaired glu-cose tolerance using lifestyle intervention and/or treatment.2-4 We

have learned from these studies that sustained changes in lifestyle in terms of physical activity and diet are crucial for successful type 2 diabetes prevention. Despite evidence of their effectiveness, it is questionable whether implementing diabetes prevention pro-grammes is feasible at a population level.5,6 Economic evaluation has demonstrated the cost effectiveness of primary prevention of type 2 diabetes using lifestyle interventions.7 However, effective implementation of diabetes prevention programmes into clinical practice remains challenging and requires significant financial and human resources.6

Rigorous scientific evaluation of the programmes, prior to large-scale implementation, is fundamental for demonstrating programme effectiveness and feasibility, determining whether or not they are cost effective and providing information for improving existing programmes and designing new ones. Lifestyle modifica-tion programmes are usually evaluated through randomised con-trolled trials that compare the effects of the lifestyle programme versus standard diabetes education using objective measures such as HbA1C, weight reduction and exercise measurement. Unfor-tunately, many of these evaluation studies do not integrate the patient perspective in their measurement; however, this perspective is fundamental to fully understand the benefits of the intervention programme for patients, increase patient engagement in their care and, ultimately, to maintain behaviour change. Incorporating well-designed PRO instruments is the best way to assess the effect of intervention from a patient perspective.8 However, to be credible measures, PRO instruments have to be developed and validated following a rigorous and standardised process as recommended in recent US Food and Drug Administration guidelines8 and a Euro-pean Medicines Evaluation Agency reflection paper.9

This paper addresses two questions, firstly what are the relevant outcomes of diabetes lifestyle intervention programmes from a patient perspective, and secondly what are the most appropriate existing PRO instruments to assess these outcomes?

Correspondence to: Carla Dias BarbosaMapi Values 27, Rue de la Villette 69003 Lyon, France.Tel: +33 (0)4 72 13 66 56; Fax: +33 (0)4 72 13 51 40e-mail: [email protected]

Benoit ArnouldMapi Values, Lyon, France.

Jean Bernard GruenbergerNovartis Pharma AG, Department of Health Economics and OutcomesResearch, Basel, Switzerland.

Peter EH SchwarzDivision of Prevention on Care of Type 2 Diabetes, Department of InternalMedicine III, Medical Faculty of Carl Gustav Carus, Technical UniversityDresden, Germany.

Originally in: Br J Diabetes Vasc Dis 2011; 11: 187–192


Abbreviations and acronyms

ADS Appraisal of Diabetes Scale

ATT Psychological Adjustment to Diabetes Scale

DES-SF Diabetes Empowerment Scale, Short Form

DMSES Diabetes Management Self-Efficacy Scale

HbA1C glycated haemoglobin

HCP healthcare professional

MEI Motivation and Energy Inventory

PAID problem areas in diabetes

PRO patient-reported outcomes

ProQolid Patient-Reported Outcome and Quality of Life Instruments Database

150 VOLUME 8 NUMBER 4 • NOVEMBER 2011

ACHIEVING BEST PRACTICE SA JOURNAL OF DIABETES & VASCULAR DISEASE

Table 1. Key appraisal criteria used to evaluate PRO instruments

Questionnaire property Specific criteria Explanation

Development methods Patient interviews in population Were exploratory interviews carried out in the patient population during the development of the instrument?

Evidence of comprehension in Were comprehension tests carried out in the population during the development patient population of the instrument?

Content validity Specificity of items for measuring Do the items ask specific or general questions? Are the items worded in a way that concept in targeted population relates to patients’ experience?

Richness of concept coverage Do all items in the questionnaire together cover the concept of interest?

Ability to detect differences over time Does the questionnaire appear to be sensitive to changes over time given its wording?

Appropriateness of recall period Is the recall period suitable for the study design?

Standard credibility Populations in which used Is the questionnaire used in the targeted population?

Specific application in which used Is the questionnaire used in similar programmes?

Psychometric properties Construct validity Is there any evidence that the internal structure is consistent?

Reliability: internal consistency Are the various items of the score non-redundant?

Reliability: test-retest Do two independent evaluations by the same patient give the same results?

Sensitivity to change: responsiveness Is the score able to detect changes over time?

Assessing diabetes lifestyle programmes from a patient perspectiveTo successfully assess the outcomes of lifestyle intervention pro-grammes from a patient perspective, relevant key patient outcomes most attributable to the programme must first be identified, fol-lowed by a critical review of PRO instruments that would best allow their measurement.

Key patient outcomes should be identified with careful consider-ation of the programme-based theory, the programme objectives, the expected outcomes perceptible by patients, and the target population.

The identification and selection of PRO instruments should then follow a structured approach:• identification of PRO instruments from a literature review and

consultation with experts• development of appraisal criteria from published documents on

the development and validation of health status measures10,11 and with expert psychometric advice

• critical appraisal of the identified instruments for relevance, content validity and credibility of quantitative and qualitative methods used for its development and validation. The key appraisal criteria are summarised in Table 1.

Question 1: What are the relevant outcomes of diabetes lifestyle programmes from a patient perspective?For diabetes lifestyle-modification programmes based on empirically supported theoretical models such as Prochaska’s transtheoretical model of behaviour change,12 the behavioural change theory should drive the hypotheses to test for programme evaluation. Prochaska and DiClemente suggest that behavioural change occurs in five distinct stages (precontemplation, contemplation, preparation, action and maintenance) and that movement through these stages is a cyclical or spiral process that involves both progress and periodic relapse. The stabilisation of behaviour change and the avoidance of relapse are characteristic of long-term maintenance of lifestyle behaviour change.

Such transtheoretical model-based lifestyle interventions in dia-betes aim to:• prepare and motivate patients for taking an active role in chang-

ing their lifestyle (preparation phase)• support them in making good choices and positive changes in

their lifestyle (action phase)• support them in maintaining behaviour change (maintenance

phase). These interventions are generally proposed to patients ready to change their lifestyle (patients in the preparation or action phases).

In this context, the key patient-relevant outcomes identified as most predictive of such programme success and sustained behav-iour change are psychological adjustment to diabetes, motivation to change and self-efficacy.

Psychological adjustment is the mental response of a person to a dreadful life situation. This concept covers the cognitive and behav-ioural strategies patients may use to deal with and manage their disease.13 A positive change on psychological adjustment to diabe-tes is expected as a result of lifestyle-modification programmes.

Motivation is the psychological feature that stimulates a person to action toward a desired goal. Motivation plays an important role in successful behavioural change12 and is thus identified as a key concept to evaluate the benefit of a lifestyle programme on patients.

Self-efficacy is a person’s perception of their ability to plan and take action to reach a particular goal.14 Self-efficacy was identi-fied as a key concept in order to document and monitor patients’ perceptions of their ability to plan and take action to reach their goals, in this case, eating a healthy diet and increasing physical activities.

Question 2: What are the most appropriate PRO instruments to assess lifestyle programmes in type 2 diabetes?PRO instruments were identified using ProQolid and published lit-erature reviews.15,16 The search was supplemented with instruments recommended by clinical and PRO experts.



Table 2. Description of patient-reported outcomes instruments (n = 6)

Acronym Full name of the Availability of full scale Languages Dimensions(number of items) questionnaire

ADS Appraisal of Diabetes Carey et al. Reliability and Original language: US English One dimension(n = 7) Scale validity of the appraisal of No translations Stressful impact of diabetes diabetes scale. J Behav Med 1991;14:43-51 www.musc.edu/dfm/ RCMAR/ADS.html

ATT39 Psychological Adjustment Bradley (1994) in Handbook Original language: UK English 39-item scale. Six dimensions:(n = 39) to Diabetes Scale of Psychology and Diabetes Translations: German, Greek, perceived levels of stress,ATT19 (224-26 and 230-31, Canadian English, French and adaptation, guilt, alienation,(n = 19) respectively) Italian illness conviction, and tolerance for ambiguity 19-item scale. One dimension: diabetes integration

PAID Problem Areas in Polonsky et al. Assessment Original language: US English Four dimensions: diabetes-(n = 20) Diabetes scale of diabetes-related distress. Translations: Chinese, Danish, related emotional problems, Diabetes Care Dutch, Finnish, German, treatment-related problems, 1995;18:54-60. Japanese, Portuguese, food-related problems and www.pedsql.org Portuguese for Brazil, Spanish social support-related problems

MEI Motivation and Energy From author: SE Fehnel, RTI Original language: US English Three dimensions: mentalLong-form Inventory Health Solutions, RTI More than 30 translations energy, social motivation(n = 27) International, Research available and physical energyShort-form Triangle Park, NC 27709-(n = 18) 2194, USA. [email protected]

DES-SF Diabetes Empowerment MDRTC, www.med.umich. Original language: US English Eight dimensions: need for(n = 8) Scale Short Form edu/mdrtc/ Translations: Chinese, Spanish change, developing a plan, overcoming barriers, asking for support, supporting oneself, coping with emotion, motivating oneself, making diabetes care choices appropriate for one’s priorities and circumstances

DMSES Diabetes Management From author: Dr. Jan Original language: Dutch Different structure(n = 20) Self Efficacy Scale McDowell, Queensland Translations: UK English, English according to language University of Technology, for Australia, Turkish and version (three to four Australia. j.mcdowell@qut. Chinese dimensions edu.au

Of the numerous questionnaires identified, only six instruments were found that addressed psychological adjustment, motivation and self-efficacy and had documented evidence of development methodology and psychometric properties. Three of these assessed indicators of psychological adjustment: the PAID scale,17-19 the ADS20 and the ATT-39/ATT-19.21,22 One measure assessed motivation: the MEI.23 Two measured self-efficacy: the DES-SF24,25 and the DMSES.26-29 These instruments are briefly described in Table 2.

Measures assessing psychological adjustmentOf the three measures of psychological adjustment, only the PAID satisfies all criteria. The PAID demonstrates evidence of adequate psychometric testing, responsiveness to change through similar educational intervention19,30-32 and appropriateness to the targeted type 2 diabetes population. In addition, patients were involved in its

development and comprehension testing. The ADS and ATT-39/19 are acceptable tools and meet all except one or two key appraisal criteria. The ADS has interesting content; however, its develop-ment did not involve patients and no responsiveness and sensitiv-ity to change data following similar educational interventions are available. The ATT-39 is relatively long (39 items), which can be a burden for patients; it has an item scaling that is often criticised, as respondents are faced with cognitively complex tasks (such as disagree that weight-control is not a problem for them). The ATT-19 is at a relatively early stage of development and more information is needed to assess its sensitivity to detect change in patient psycho-logical adjustment following educational intervention.

Measures assessing motivationThe MEI instrument is the only identified instrument that assesses


ACHIEVING BEST PRACTICE SA JOURNAL OF DIABETES & VASCULAR DISEASE

Key messages

• Integrating the patient perspective into lifestyle programme evaluation is fundamental to demonstrating the benefits of the programmes for patients. It also provides valuable feed-back for HCPs and helps them collaborate with patients to manage diabetes over the course of the disease

• Key patient-relevant concepts of greatest interest for life-style programme evaluation from a patient perspective are psychological adjustment to diabetes, motivation to change and self-efficacy

• Among existing, well-validated instruments, the PAID, MEI and DMSES scales appear to be the instruments of choice to assess the effect of type 2 diabetes lifestyle programmes on patients’ behaviours and perceptions

motivation. It is created to be both responsive to treatment effects and able to discriminate among patients with different clinical char-acteristics.23 Although the MEI was developed through focus groups and cognitive interviews with individuals being treated for depres-sion, all items are carefully worded to be applicable across various populations, including diabetes patients. The MEI short form, with a recall period of the previous seven days, is expected to be sensi-tive to behavioural modification programmes and can be used to compare the motivation levels of type 2 diabetic patients over the course of lifestyle intervention programmes.

Measures assessing self-efficacyTwo potential candidates to assess self-efficacy were found and meet most of the appraisal criteria: the DES-SF and the DMSES. Although the DES-SF offers comprehensive and coherent coverage of the self-efficacy concept and shows interesting results in educational pro-gramme assessment,33-35 the item wording and the item scaling are complex and require considerable cognitive effort from the patients to answer the questions. The DMSES is preferred for its simplicity, although further research on this instrument is warranted to assess its responsiveness over time. This instrument showed a small improve-ment in confidence in self-care following an educational intervention in primary care in patients with type 2 diabetes.32

ConclusionHealth-related quality of life, patient satisfaction, and patient adher-ence to treatment are important PROs that should improve when using well-designed lifestyle-modification programmes. However, when assessing the effectiveness of a new programme, the primary focus of assessment should be measurable, observable changes at the patient level, which are specific and direct outcomes of the inter-vention.

Psychological adjustment, motivation and self-efficacy are key patient-relevant concepts to consider when evaluating transtheoretical model-based lifestyle interventions in diabetes from a patient perspective. Specific validated instruments exist, which reliably assess these key concepts. Of the instruments identified in

our work, the PAID, the MEI and the DMSES questionnaires are the best existing candidates to assess psychological adjustment, motivation to change and self-efficacy, respectively.

After evaluation, programmes that have shown beneficial effects at patient level and that have proved to be well designed and cost effective can be generalised and implemented in clinical practice settings. Indeed, setting goals, providing patient education for achieving these goals, and monitoring the patient’s progress using PRO instruments adapted to the context of clinical practice, are critical in clinical practice for maintenance of healthy behav-iours, as well as supporting patient adherence and persistence to pharmacological therapies.

ReferencesInternational Diabetes Federation. Diabetes and Impaired Glucose Tolerance. 1. Global Burden: Prevalence and Projections, 2010 and 2030. www.diabetesatlas.org/content/diabetes-and-impaired-glucosetolerance (last accessed 16 March 2011).Knowler WC, Barrett-Connor E, Fowler SE, 2. et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403.Pan XR, Li GW, Hu YH et al. Effects of diet and exercise in preventing NIDDM in 3. people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20: 537–44.Tuomilehto J, Lindstrom J, Eriksson JG 4. et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343–50.Ackermann RT, Marrero DG. Adapting the Diabetes Prevention Program lifestyle 5. intervention for delivery in the community: the YMCA model. Diabetes Educ 2007; 33: 69, 74–5, 77–8.Schwarz PE, Schwarz J, Schuppenies A, 6. et al. Development of a diabetes prevention management program for clinical practice. Publ Hlth Rep 2007; 122: 258–63.Hernan WH, Brandle M, Zhang P, 7. et al. Costs associated with the primary prevention of type 2 diabetes mellitus in the diabetes prevention program. Diabetes Care 2003; 26: 36–47.U.S.Department of Health and Human Services, Food and Drug Administration, 8. Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, Center for Devices and Radiological Health. Guidance for industry. Patient-reported outcome measures: use in medical product development to support labeling claims. www.fda. gov/downloads/Drugs/GuidanceCompliance RegulatoryInformation/Guidances/UCM193282.pdf (last accessed 21 March 2011).European Medicines Agency. Reflection Paper on the Regulatory Guidance for 9. the Use of Health-Related Quality of Life (HRQL) Measures in the Evaluation of Medicinal Products. Doc.Ref. EMEA/ CHMP/EWP/139391/2004. www.emea.europa.eu/pdfs/human/ewp/13939104en.pdf (last accessed 29 July 2009).Lohr KN. Assessing health status and quality-of-life instruments: attributes and 10. review criteria. Qual Life Res 2002; 11: 193–205.Terwee CB, Bot SD, de Boer MR, 11. et al. Quality criteria were proposed for measurement properties of health status questionnaires. J Clin Epidemiol 2007; 60: 34–42.Prochaska JO, Diclemente CC, Norcross JC. In search of how people change. 12. Applications to addictive behaviors. Am Psychol 1992; 47: 1102–14.Lazarus RS, Folkman S. 13. Stress, Appraisal, and Coping. New York: Springer, 1984.Bandura A. The anatomy of stages of change. 14. Am J Health Promot 1997; 12: 8–10.Duke SA, Colagiuri S, Colagiuri R. Individual patient education for people with 15. type 2 diabetes mellitus. Cochrane Database Syst Rev 2009: CD005268.Eigenmann CA, Colagiuri R, Skinner TC, Trevena L. Are current psychometric 16. tools suitable for measuring outcomes of diabetes education? Diabet Med 2009; 26: 425–36.Polonsky WH, Anderson BJ, Lohrer PA, 17. et al. Assessment of diabetes-related distress. Diabetes Care 1995; 18: 754–60.Welch G, Jacobson AM, Polonsky WH. The Problems Areas in Diabetes Scale. An 18. evaluation of its clinical utility. Diabetes Care 1997; 20: 760.Welch G, Weinger K, Anderson BJ, Polonsky WH. Responsiveness of the Problem 19. Areas In Diabetes (PAID) questionnaire. Diabet Med 2003; 20: 69–72.Carey MP, Jorgensen RS, Weinstock RS. Reliability and validity of the Appraisal of 20. Diabetes Scale. J Behav Med 1991; 14: 43–50.


Dunn SM, Smartt HH, Beeney LJ, Turtle JR. Measurement of emotional adjustment 21. in diabetic patients: validity and reliability of ATT39. Diabetes Care 1986; 9: 480–489.Welch G, Dunn SM, Beeney LJ. The ATT39: a measure of psychosocial adjustment 22. to diabetes. In: Bradley C (ed). Handbook of Psychology and Diabetes. Amsterdam: Hardwood Academic Publishers, 1984; 223–44.Fehnel SE, Bann CM, Hogue SL, 23. et al. The development and psychometric evaluation of the Motivation and Energy Inventory (MEI). Qual Life Res 2004; 13: 1321–36.Anderson RM, Fitzgerald JT, Funnell MM, Gruppen LD. The third version of the 24. Diabetes Attitude Scale. Diabetes Care 1998; 21: 1403–7.Anderson RM, Funnell MM, Fitzgerald JT, Marrero DG. The Diabetes 25. Empowerment Scale: a measure of psychosocial self-efficacy. Diabetes Care 2000; 23: 739–43.Bijl JV, Poelgeest-Eeltink AV, Shortridge-Baggett L. The psychometric properties 26. of the diabetes management self-efficacy scale for patients with type 2 diabetes mellitus. J Adv Nurs 1999; 30: 352–59.Kara M, van der Bijl JJ, Shortridge-Baggett L 27. et al. Cross-cultural adaptation of the Diabetes Management Self-Efficacy Scale for patients with type 2 diabetes mellitus: scale development. Int J Nurs Stud 2006; 43: 611–21.McDowell J, Courtney M, Edwards H, Shortridge-Baggett L. Validation of the 28.

Australian/English version of the Diabetes Management Self-Efficacy Scale. Int J Nurs Pract 2005; 11: 177–84.Vivienne Wu SF, Courtney M, Edwards H, 29. et al. Development and validation of the Chinese version of the Diabetes Management Self-Efficacy Scale. Int J Nurs Stud 2008; 45: 534–42.Bastiaens H, Sunaert P, Wens J, 30. et al. Supporting diabetes self-management in primary care: pilot-study of a group-based programme focusing on diet and exercise. Prim Care Diabetes 2009; 3: 103–9.Izquierdo RE, Knudson PE, Meyer S, 31. et al. A comparison of diabetes education administered through telemedicine versus in person. Diabetes Care 2003; 26: 1002–7.Sturt JA, Whitlock S, Fox C, 32. et al. Effects of the Diabetes Manual 1:1 structured education in primary care. Diabet Med 2008; 25: 722–31.George JT, Valdovinos AP, Russell, I 33. et al. Clinical effectiveness of a brief educational intervention in Type 1 diabetes: results from the BITES (Brief Intervention in Type 1 diabetes, Education for Self-efficacy) trial. Diabet Med 2008; 25: 1447–53.Lowe J, Linjawi S, Mensch M, 34. et al. Flexible eating and flexible insulin dosing in patients with diabetes: Results of an intensive self-management course. Diabetes Res Clin Pract 2008; 80: 439–43.McCarrier KP, Ralston JD, Hirsch IB, 35. et al. Web-based collaborative care for type 1 diabetes: a pilot randomized trial. Diabetes Technol Ther 2009; 11: 211–17.

This peer-reviewed journal is available as full text at all tertiary institutions in South Africa, presenting a great opportunity to submit your

good-quality original articles for speedy publication.

Recent user research has shown that some 10 000 annual topic searches were done on the SA Journal of Diabetes & Vascular Disease database,

which contains seven years of published material.

The SA Journal of Diabetes & Vascular Disease aims to provide a forum for specialists involved in the care of people with diabetes, to exchange

information, promote better management and stimulate research in Africa.

This quarterly journal publishes original research and scholarly reviews about prevention and management of diabetes, relating to both general and

specific issues.

The SA Journal of Diabetes & Vascular Disease invites you to submit your articles online only. Read the Instructions to Authors at

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for more information on the journal’s policies and the submission process.

INSULIN RESISTANCE

OBESITY

HYPERTENSIONDYSLIPIDAEMIA

THROMBOSISATHEROSCLEROSIS

HYPERGLYCAEMIA

HYPERINSULINAEMIA

DIABETES &

VASCULAR DISEASE

Call for Articles

References: 1. CRESTOR® package insert 2. Jones P, Davidson MH, Stein EA, et al. Comparison of the Effi cacy and Safety of Rosuvastatin Versus Atorvastatin, Simvastatin, and Pravastatin Across Doses (STELLAR* Trial). Am J Cardiol 2003;92:152-160. 3. Schuster H, Barter PJ, Stender S, et al. Effects of switching statins on achievement of lipid goals. Measuring Effective Reduction in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study. Am Heart J 2004;147:705-712. 4. Rosenson RS. Statins: can the new generation make an impresssion? Expert Opin Emerg Drugs 2004;9(2):269-279. 5. Shepherd J, Hunninghake DB, Stein EA, et al. Safety of rosuvaststin. Am J Cardiol 2004;94:882-888.

S4 CRESTOR® 5 (Tablet) Each CRESTOR® 5 tablet contains 5 mg of rosuvastatin as rosuvastatin calcium. S4 CRESTOR® 10 (Tablet) Each CRESTOR® 10 tablet contains 10 mg of rosuvastatin as rosuvastatin calcium. S4 CRESTOR® 20 (Tablet) Each CRESTOR® 20 tablet contains 20 mg of rosuvastatin as rosuvastatin calcium. S4 CRESTOR® 40 (Tablet) Each CRESTOR® 40 tablet contains 40 mg of rosuvastatin as rosuvastatin calcium. PHARMACOLOGICAL CLASSIFICATION: A. 7.5 Serum-cholesterol reducers INDICATIONS: Primary hypercholesterolaemia, mixed dyslipidaemia and isolated hypertriglyceridaemia (including Fredrickson Type IIa, IIb and IV; and heterozygous familial hypercholesterolaemia) as an adjunct to diet when response to diet and exercise is inadequate. Indicated in patients with homozygous familial hypercholesterolaemia, either alone or as an adjunct to diet and other lipid lowering treatments. CRESTOR® 40 mg should only be considered in patients with severe hypercholesterolaemia and high cardiovascular risk who do not achieve their treatment goal on 20 mg of CRESTOR® or alternative therapy. Specialist supervision is recommended when the 40 mg dose is initiated. REGISTRATION NUMBERS: CRESTOR® 5: 41/7.5/0298, CRESTOR® 10: 36/7.5/0349, CRESTOR® 20: 36/7.5/0350, CRESTOR® 40: 36/7.5/0351. DETAILS OF THE REGISTERED LICENCE HOLDER: AstraZeneca Pharmaceuticals (Pty) Ltd Reg No. 1992/005854/07. No. 5 Leeuwkop Road, Sunninghill, 2157, South Africa. Tel: 011 797 6000. Fax: 011 797 6001. www.astrazeneca.co.za. For full details relating to any information mentioned above please refer to the package insert of CRESTOR® 5 mg, 10 mg, 20 mg and 40 mg. CRESTOR® is a registered trademark of AstraZeneca group. Licensed from Shionogi & Co Ltd, Osaka, Japan. EPI Date: 13/05/2008. Date compiled: March 2011.

16162

Help your patients love themselves a little more.

CRESTOR® 5 mg is suitable for select patients who need less aggressive lipid lowering1

CRESTOR® is the more effective statin at lowering LDL-C and raising HDL-C2

CRESTOR® 10 mg will get most patients to LDL-C goal1,3

CRESTOR® is well-tolerated and has a favourable benefi t-risk profi le4,5

16162 Crestor FamPractice A4Ad.indd 1 3/28/11 9:58:59 AM


SA JOURNAL OF DIABETES & VASCULAR DISEASE SPECIAL REPORT

South African patients with diabetes are under-treated for hypercholesterolaemia

T he recently published South African CEPHEUS study has shown that 46% of patients with diabetes who are treated for hypercholesterolaemia do not reach their targets for low-

density lipoprotein cholesterol (LDL-C).1 This non-interventional study known as CEPHEUS (CEntralised Pan-South African survey on tHE Under-treatment of hypercholeSterolaemia) was conducted between November 2009 and April 2010 in 69 South African study centres and evaluated patients who had received cholesterol-low-ering therapy for at least three months.

A total of 3 001 patients consented to participate in the survey with only five patients not being entered into the final data set. The study was a single-visit non-interventional study, but also included a doctor and patient questionnaire.

The doctor questionnaire was completed prior to patient recruit-ment. It evaluated the attending doctor’s views on the manage-ment of hypercholesterolaemia as seen in his/her patients, and the overall attitude to diagnosis and treatment according to dyslipidae-mia guidelines.

The patient questionnaire was completed before the investiga-tor assessed the patient. It evaluated the patient’s awareness and perceptions of hypercholesterolaemia, his/her understanding of the lipid-lowering drug (LLD) regimen and compliance with treatment.

Survey of in-treatment hypercholesterolaemia highlights the need for intensified treatment in diabetesJ AALBERS

Major centres in Johannesburg, Cape Town, Durban and Bloem-fontein led the study, with AstraZeneca sponsorship and assistance in the study design. Quintiles, a contract research organisation, pro-vided data management support.

CEPHEUS study methodsFor each patient, the investigator completed a patient record form, which included information on the patient’s demographics, current LLD treatment and reason for initiating LLD treatment. The investi-gator also recorded the presence of known cardiovascular risk fac-tors such as smoking, diabetes, family history of premature CHD (defined as definite myocardial infarction or sudden death before 55 years of age in father or other male first-degree relative, or before 65 years of age in mother or other female first-degree relative), arterial hypertension (defined as blood pressure ≥ 140/≥ 90 mmHg or current use of antihypertensive medication) and cardiovascular medical history.

Physical examination by the investigator was limited to measure-ment of height, weight, waist circumference and blood pressure. A fasting blood sample was drawn to evaluate the serum lipid profile [including measurement of apolipoprotein (Apo) AI and Apo B] and glucose levels.

It is important to note that this study deliberately attempted to ensure the inclusion of patients of all racial groups, with Caucasians being in the minority (46.2%) (Table 1). The proportion of patients achieving LDL-C target was analysed using target values from mul-tiple guidelines to allow for easy comparison with similar surveys conducted in other countries (Table 2).

Results of lipid-lowering therapy in diabetes patientsOnly slightly more than half (54.4%) of the diabetes patients reached a target LDL-C of less than 2.5 mmol/l. HbA1c level was also measured in all patients and mean HbA1c in the diabetics was 8.33%, indicating that many diabetics have inadequate glycaemic control. The mean fasting plasma glucose (FPG) in the diabetes

Table 1. Summary of demographics and patient characteristics at baseline

Study cohortPatient characteristics n = 2 996 (%)

Age (years) 59.4 (11.4)Gender Male 1572 (52.5) Female 1424 (47.5)

Ethnic group Caucasian 1385 (46.2) Non-Caucasian 1611 (53.8) Black 510 (17.0) Mixed ancestry 481 (16.1) Indian 576 (19.2) Asian 44 (1.5)

BMI (kg/m2) 30.0 (6.0)Waist circumference (cm) 101.0 (14.1)SBP (mmHg) 133.2 (17.7)DBP (mmHg) 80.2 (9.9)Current smoker 445 (14.9)Diagnosed diabetes 1411 (47.1)Undiagnosed diabetes 71 (2.4)Diabetes and history of coronary heart disease 494 (16.5)

Table 2. LDL-C goal-achievement targets

Risk category

NCEP ATP III/2004 NCEP

ATP IIIEuropean

JEFT IVSouth

African

High risk

Current goal (mmol/l) < 2.6 < 2.5 < 2.5

Optional goal (mmol/l) < 1.8 < 2.0 –

Medium/low risk

Current goal (mmol/l) < 3.4 < 3.0 < 3.0


SPECIAL REPORT SA JOURNAL OF DIABETES & VASCULAR DISEASE

Key take-home messages

• In South Africa, only 50% of diabetes patients reached the target LDL-C of < 2.5 mmol/l.

• Lipid levels are often not checked and medication adjusted following the initial prescription.

• Patients who reported high treatment adherence were more likely to reach target.

• Patients in the 55–70-year age range were more likely to reach target than those under 40, likely due to better adher-ence.

• Many diabetics require high-dose statins or combination lipid-lowering therapy to reach LDL-C targets.

Table 4. Patients on statins achieving the LDL-C goals

Atorvastatin Fluvastatin Lovastatin Pravastatin Rosuvastatin Simvastatin

(n = 866) (n = 10) (n = 4) (n = 43) (n = 371) (n = 1 526)

Mean dosage (mg) 20.6 44.0 17.5 23.6 14.7 21.7

Controlled LDL-C NCEP* (%) 62 60 25 44 71 59

Controlled LDL-C Eu/SA* (%) 53 30 25 33 61 52

*Chi-square test; p < 0.05

Table 3. Patients achieving the LDL-C goals recommended by the guidelines.

European/South African guidelinesPatient characteristics n (%)

Overall survey 1557 (52.3)

Age (years) < 40 52 (36.1) 40–54 382 (48.5) 55–69 822 (54.5) ≥ 70 301 (56.2)

Gender Male 854 (54.7) Female 706 (49.6)

Body mass index (kg/m2) Normal weight (< 25 kg/m2) 293 (51.3) Overweight (25–29 kg/m2) 584 (54.0) Obese (≥ 30 kg/m2) 678 (51.4)

Coronary heart disease 532 (50.4)

Peripheral artery disease 69 (47.3)

Cerebrovascular atherosclerotic disease 81 (52.3)

Current smoker 213 (48.2)

Diabetes 764 (54.4)

Arterial hypertension 1136 (53.4)

Family history of premature 391 (45.3)cardiovascular disease

Type of prevention Primary prevention 722 (54.8) Secondary prevention 437 (50.6) Diabetes mellitus 364 (54.6) Familial hypercholesterolaemia 34 (26.4)

Metabolic syndrome (Alberti et al. 2009) 1031 (50.9)

Type of therapy Statin monotherapy 1485 (53.0) Fibrates monotherapy 7 (28.0) Combination therapy 53 (43.8)

Risk category High risk 1086 (50.2) Medium/low risk 471 (57.9)

patients was correspondingly high at 8.16 mmol/l. Only 50% of patients with the metabolic syndrome reached their LDL-C goal of less than 2.5 mmol/l (Table 3).

One of the most important lessons for clinical practice from this study is that lipid-lowering therapy was frequently left unaltered, with a total of 63% of patients still on the same agent and dose that they started on. Table 4 lists goal achievement on and the mean dosage according to the statin prescribed.

The physician survey showed that most doctors used the South African guidelines. Their failure to treat to target may have been due to additional concerns about drug toxicity, drug formulary con-straints, and failure to check lipid levels once LLDs had been started and to titrate LLD dosage when required.

Patients showed a good understanding of the need to take their medication, particularly among patients who had had previous car-diovascular events.

Julia Aalbers, Special Assignments Editor

ReferenceRaal F, Schamroth C, Blom D, Marx J, Rajput M, Haus M, 1. et al. CEPHEUS SA: a South African survey on the under-treatment of hypercholesterolaemia. Cardiovasc J Afr 2011; 22(5): 234–242. Advance published, September 2011.


SA JOURNAL OF DIABETES & VASCULAR DISEASE SPECIAL REPORT

New guidelines recommend lower LDL target in high-risk cardiovascular patientsPETER WAGENAAR

T he South African Heart Association and the Lipid and Atherosclerosis Soci-

ety of Southern Africa (LASSA) held their second joint guide-line collaboration meeting on 15 and 16 October 2011. The meeting was attended by rep-resentatives of both societies, the funding industry and the Department of Health, as well as various medical specialists. With a view to optimising the management of cardiovascular disease in South Africa, both societies adopted the European Society of Cardiology (ESC)/European Atherosclerosis Soci-ety (EAS) dyslipidaemia guide-lines published in the European Heart Journal in June 2011.1 These guidelines are now also

the official South African guidelines to determine the most effec-tive and appropriate diagnostic tests and treatments for dyslipidae-mic cardiovascular disease. ‘However, we will be tailoring certain dietary recommendations to our own ethnic groups. A major difference is that we won’t be using the SCORE risk assessment

system, which was developed based on European epidemiological data’, said Dr Eric Klug, vice president of the South African Heart Association.

‘Because South Africa has no comparable data, we’ve always used the Framingham system and will be adopting the new Fram-ingham system in future. Women’s risk was underestimated by the old Framingham system, but the new system has addressed that, in addition to taking the risk of younger people into account. They can now be assessed more accurately.’

The key change in the new guidelines is the downward revi-sion of the target LDL cholesterol level in very high-risk patients (> 30% Framingham risk). It has been lowered to 1.8 mmol/l from 2.6 mmol/l. The definition of ‘very high risk’ has also been expanded to include chronic kidney disease (CKD) in addition to diabetes, established vascular disease (including previous stroke or heart attack) and familial hypercholesterolaemia. CKD, defined as a glomerular filtration rate < 60 ml/minute/1.73m2 for a period of more than three months, is now considered a major cardiovascular risk factor in its own right. In addition, the threshold for ‘high risk’ is now defined as > 15% Framingham risk and the LDL target in that group is < 2.5 mmol/l (Tables 1, 2).1

‘The INTERHEART study, published in the Lancet in 2004,2 and to which Africa contributed 5% of the 30 000 patients involved, showed that the serum HDL:LDL ratio topped the odds ratio charts in predicting future myocardial infarction. It is therefore a major cardiovascular risk factor which, uncontrolled, will lead to a sig-nificantly greater burden of disease’, says Dr Klug. ‘Atherosclerotic cardiovascular disease is the global number one killer and the man-

Table 2. Recommendations for treatment targets for LDL-C

Recommendations Class a Level b

In patients at VERY HIGH cardiovascular risk (established cardiovascular disease, type 2 diabe-tes, type 1 diabetes with target-organ damage, moderate to severe CKD or a Framingham score level ≥ 30%) the LDL-C goal is < 1.8 mmol/l and/or ≥ 50% LDL-C reduction when target level cannot be reached.

1 A

In patients at HIGH cardiovascular risk (markedly elevated single risk factor, a Framingham score level ≥ 15 to < 30%) an LDL-C goal < 2.5 mmol/l should be considered.

11a A

In subjects at MODERATE cardiovascular risk (Framingham score level ≥ 3% and < 15%) an LDL-C goal < 3.0 mmol/l should be considered.

Low risk (Framingham score level < 3%).

aClass of recommendation; blevel of evidence.

Amended from ESC/EAS guidelines.1

11a C

Table 1. Recommendations for lipid profiling in order to assess total cardiovascular risk

Condition Classa Levelb

Lipid profiling is indicated in subjects with:Type 2 diabetes mellitus

1 C

Established cardiovascular disease 1 C

Hypertension 1 C

Smoking 1 C

BMI ≥ 30 kg/m2 or waist circumference > 94 cm (90 cmc) for men, > 80 cm for women

1 C

Family history of premature cardiovascular disease 1 C

Chronic inflammatory disease 1 C

Chronic kidney disease 1 C

Family history of familial dyslipidaemia 1 C

Lipid profiling may be considered in men > 40 and women > 50 years of age

11b C

SA Guideline Committee has added HIV-positive patients on antiretroviral therapy

1 C

aClass of recommendation; blevel of evidence; cfor Asian males.BMI = body mass index.

Amended from ESC/EAS guidelines.1

Dr Eric Klug


SPECIAL REPORT SA JOURNAL OF DIABETES & VASCULAR DISEASE

agement of dyslipidaemia is therefore vital to addressing the epi-demic. We and LASSA are committed to engaging meaningfully with patients and re-establishing the central role of the medical profession in its evaluation, diagnosis and management.’

The new guidelines also take into account the implications of HIV/AIDS for dyslipidaemia in South Africa. HIV/AIDS is associated with abnormal lipid profiles in some patients and certain antiretrovirals

(ARVs) can exacerbate matters. Already, simvastatin cannot be used in patients on protease inhibitors and the US Food and Drug Admin-istration has now issued an official warning applicable to all patients, regardless of HIV status, that the 80-mg dose not be used in future. Stable patients currently taking 80 mg with no adverse muscular effects can be maintained on the dose. However, physicians need to maintain heightened awareness of potential drug interactions when adding any new medications to a patient’s regimen.

The SA Heart Association is affiliated to the ESC and Dr Marja-Riitta Taskinen, emeritus professor of medicine at the University of Helsinki and a member of the EAS guideline committee, was present at the local meeting to advise the SA Heart Association and LASSA. ‘It therefore behoves us to follow its guidelines and not change them’, says Dr Klug.

The challenge now is to disseminate the new guidelines effec-tively to the widest possible audience and the associations are look-ing to embark on a sustainable marketing campaign in this regard. ‘Strategies to achieve this, including how to reach the “non-con-verted”, were also discussed at the meeting’, concludes Dr Klug.

Peter Wagenaar, Gauteng correspondent

ReferencesTask Force for the management of dyslipidaemias of the European Society of 1. Cardiology (ESC) and the European Atherosclerosis Society (EAS). ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2011; 32(14): 1769–1818. Published online June 28, 2011. doi: 10.1093/eurheartj/ehr158. Rosengren A, Hawken S, Ounpuu S, Sliwa K, Zubaid M, Almahmeed WA, 2. et al; INTERHEART investigators. Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364(9438): 953–962. PMID: 15364186 [PubMed - indexed for MEDLINE].

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The International Society of Cardiovascular Disease Epidemiol-ogy and Prevention announces the 44th 10-day international teaching seminar on cardiovascular disease epidemiology and prevention to be held 15–27 January 2012 in Cape Town, South Africa in conjunction with the South African Medical Research Council and the University of Cape Town.

Approximately 36 Fellows can be accepted. The Society’s seminar committee will make the final selection. Nominees should ideally be at the postgraduate level with residency train-ing or its equivalent, and be interested in cardiovascular disease epidemiology.

Normally, preference is given to younger candidates, with little or no formal training in epidemiology. Tuition, board and accommodation are provided without cost to fellows. Fellows and their sponsors are responsible for their own travel costs to the seminar.

International Society of Cardiovascular Disease Epidemiology and Prevention

44th 10-day International Teaching Seminar on Cardiovascular DiseaseEpidemiology and Prevention

15–27 January 2012Cape Town, South Africa

FLUENCY IN ENGLISH IS AN ABSOLUTE ESSENTIALShould any accepted Fellow be unable to attend, no substitute not reviewed by the seminar committee may be sent as an alternate by the institution.

Applications, including (1) a letter of nomination by the chief of department or institution, or other relevant sponsor, (2) a personal letter of application from the nominee, and (3) the applicant’s cur-riculum vitae, should be received before 15 September 2011 by the seminar coordinator, address below. Applications can be sent by e-mail but a signed hard copy should follow in the post.

Professor Kay-Tee Khaw, Clinical Gerontology Unit, PO Box 251, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge CB2 2QQ, England

Fax: +44-1223-336928 • Tel: +44-1223-217292e-mail: [email protected]


SA JOURNAL OF DIABETES & VASCULAR DISEASE NUTRITION FOCUS

Avoid these fatsIntroduction to South African legislation on trans fatty acids

In October 2009, the Department of Health started consult-ing with stakeholders in order to develop legislation aimed at reducing trans fatty acids derived from partial hydrogenation of

vegetable oil used in some foods sold in South Africa. In February 2011, the Foodstuffs, Cosmetic and Disinfectants act of 1972 (act 54 of 1972), as printed in the Government Gazette on 1 March 2010, was amended to include regulations related to trans fats in foodstuffs.

On 12 September 2011, Health Minster Dr Aaron Motsoaledi stated at a summit in Boksburg on non-communicable diseases, that the amounts of artificial trans fatty acids found in food should be limited according to legislation. In a written reply to a parlia-mentary question regarding the new regulations, it was stated that ‘these regulations prohibit the sale, manufacturing and importa-tion of any oils and fats containing partial hydrogenated fats and oils, also referred to as “trans-fats”, in processed foods [with] two grams per 100 g thereof’. Food companies that produce products containing more than the allowed amount of trans fatty acids as stipulated will either have to remove these products from the market, or alter the manufacturing methods and ingredients to comply with the new regulations.

The Nutrition Information Centre of the University of Stellen-bosch (NICUS) supports the actions of the Department of Health to regulate the trans fatty acid levels of foods to follow in the foot-steps of countries such as Denmark and the USA who have already implemented trans fatty acid regulations. The reduction of trans fatty acids in foods will reduce the risk of chronic diseases of life-style associated with trans fatty acids.

The latest changes in the Foodstuffs, Cosmetic and Disinfectants act of 1972 (act 54 of 1972) creates an opportunity for the Depart-ment of Health to assume a central role in implementing regulatory measures that would reduce the intake of artificial trans fatty acids. However, consumers should still make informed choices when choosing foods for themselves and their families, by reading food

labels. A healthy diet, that includes foods low in fat and trans fatty acids, should be a priority for all South Africans in order to reduce health risks and increase quality of life.

What are trans fatty acids?Fats found in food can be classified as saturated, mono- and polyunsaturated fatty acids. Saturated fats are derived mostly from animal products and the unsaturated fats are plant based. Trans fatty acids (TFA) occur naturally in products of animal origin, although to a limited extent. TFA are present in ruminant meat (beef) and milk fats as a result of bio-hydrogenation of unsaturated fatty acids in the rumen. The major trans fatty acid in ruminant meat and milk is vaccenic, with smaller amounts of other trans fatty acids.

Processing of vegetable oils such as sunflower oil changes the unsaturated fatty acids into trans fatty acids. This processing is called hydrogenation. Through the process of hydrogenation, pre-viously unsaturated fats become partially or completely saturated. These hydrogenated fats do not occur naturally in food, and are therefore artificial.

Why are there trans fatty acids in food?Products such as cakes, commercial cookies, chips, pies, dough-nuts, fried chicken and fish nuggets as well as savoury snack foods such as popcorn, crisps and crackers are made with partially hydro-genated vegetable oils. Traditional vegetable shortening or brick margarine contains trans fatty acids that are formed during produc-tion and are therefore artificial trans fatty acids.

Trans fatty acids are used by the food industry as they have a higher melting point, which makes them more attractive for baking, and the saturation of these fats extends the shelf life of

Table 1. Recommended amounts of fatty acids in the diet.

Dietary factorSouth African goal (% of total energy, unless otherwise stated)

Total fat Up to 30% of energy intake

Saturated fatty acids (SFAs) < 10% of energy< 7% for those at risk of cardiovascular disease

Polyunsaturated fatty acids (PUFAs) 6–10%

n-6 polyunsaturated fatty acids (PUFAs)

5–8%

n-3 polyunsaturated fatty acids (PUFAs)

1–2%

Trans fatty acids < 1%

Mono-unsaturated fatty acids (MUFAs)

By difference*

*MUFA = total fat – (SFA + PUFA + TFAs). Therefore, the MUFA intake result-ing may cover a wide range depending on the total fat intake and dietary fatty acid pattern.

Healthy fats


NUTRITION FOCUS SA JOURNAL OF DIABETES & VASCULAR DISEASE

Fig. 1. Food labels give the breakdown of carbohydrates, fats and proteins in the food.

Nutrition FactsServing size 1 cup (200 g)

Amount per serving

Calories 260

% Daily value

Fat 13g 20%

Saturated fat 3 g 25% + Trans fat 2 g

Cholesterol 30 mg 10%

Sodium 660 mg 28%

Carbohydrate 31 g 10%

Fiber 0 g 0%

Sugars 5 g

Protein 5 g

Vitamin A 4% Vitamin C 2%

Unhealthy fats

baked products. Pressure from health authorities and consumers to decrease the amounts of saturated fats in foods prompted the food industry to replace some of the saturated fats with a stable form of unsaturated fats, resulting in an increase of trans fatty acids in foods.

Why do we need to reduce the amount of trans fatty acids in our diets? Trans fatty acids are not essential and have no proven health ben-efits. A large consumption of trans fatty acids leads to increased weight gain. The overweight or obesity associated with trans fatty acid consumption, as well as the actual intake of trans fatty acids lead to an increase in low-density lipoprotein (LDL) (bad) cholesterol and a decrease in high-density lipoprotein (HDL) (good) cholesterol. Higher LDL cholesterol and decreased HDL cholesterol is a major risk factor for chronic diseases of lifestyle such as heart disease, the metabolic syndrome and diabetes mellitus.

The most recent South African demographic and health survey from 2003 showed that the self-reported prevalence of heart dis-ease was 2.7% for men and 4% for women; 2.6% of men reported having diabetes, while the prevalence was reported as 3.9% in women. Elevated levels of serum trans fatty acids have been associ-ated with increased risk of breast and prostate cancer.

How much fat can you consume daily?Recent evidence indicates that diets with adequate energy, providing less than 30% of energy from fat, are sufficient to promote normal growth and normal sexual maturation but protect against chronic diseases of lifestyle. Most of the fat in the diet should come from foods that are sources of poly- and/or mono-unsaturated fatty acids such as fish, nuts and vegetable oils, with less fat that is derived from animal products, processed foods and snacks (Table 1).

How much trans fatty acids can you safely consume?According to goals set out for South Africans, trans fatty acids should make up no more than 1% of one’s total daily energy intake. For example, a moderately active 30-year-old woman, 1.65 m tall with a healthy body weight of 61 kg, requires 8 828 kJ

ConclusionTrans fatty acids occur naturally in some foods, but the majority of trans fatty acids consumed come from foods that are baked, fried or prepared with hydrogenated fats. Trans fatty acids are not essential and a high intake is dangerous to our health. Consumers should read food labels when purchasing food for themselves and their families, and look out for the term ‘partially hydrogenated vegetable oil’ in the ingredients list, as this shows that the product contains trans fatty acids. Choose products that are free or virtually free (≤ 0.1 g per 100 g) of trans fatty acids. A healthy diet that includes foods low in fat and trans fatty acids should be a priority for all South Africans in order to reduce health risks and increase quality of life.

For further personalised and more detailed information, please contact NICUS or your specialist.

Source: Selected extraction from Facts about trans fatty acids, the NICUS 2011. Available at www.sun.ac.za/nicus.

per day. She can therefore consume a maximum of 2.3 g trans fatty acids per day.

How can you reduce the amounts of trans fatty acids in your diet? Reducing total fat intake is important and will in effect reduce your trans fatty acid intake. Opt for liquid vegetable oils such as canola, olive and sunflower oils instead of animal fat such as lard, ghee and butter. Choose soft margarines that are sold in tubs over butter, brick margarine and baking shortening. Soft margarines are high in polyunsaturated fatty acids and typically contain no or very low levels of TFA.

Read product labels and choose products free or virtually free (≤ 0.1 g per 100 g) of trans fatty acids. Limit your intake of snacks and confectionary products. Be aware of the term ‘partially hydro-genated vegetable oil’ on ingredients lists of food products and avoid those foods (this refers to trans fatty acids) (Fig. 1).

SA JOURNAL OF DIABETES & VASCULAR DISEASE


Case Study 1

Type 2 diabeTes paTienT wiThouT CVd, noT aChieVing lipid TargeTs

Clinical studies suggest that people with

type 2 diabetes without cardiovascular dis-

ease (CVD) are at the same high risk of a

CVD event as those without diabetes but with CVD,

although whether this risk is equivalent is disputed by

other studies. Despite this, there is clear consensus

that individuals with type 2 diabetes should nearly

always be considered as being in the high CVD risk

category.

This excess risk is independently associated with

hyperglycaemia together with high blood pressure

and dyslipidaemia – typically low HDL cholesterol and

elevated triglycerides – which are all components

of the metabolic syndrome that is common in

these patients. It is important, therefore, that type

2 diabetes patients achieve guideline lipid targets

(4 mmol/l for total cholesterol and 1.8 mmol/l for

LDL cholesterol) to reduce their risk of CVD events.

The management of type 2 diabetes patients with

co-existent metabolic syndrome such as James (see

Presented by Prof Michael Kirby

Visiting Professor, Faculty of Health and

Human Sciences, Centre for Research

in Primary and Community Care and

the Clinical Trials Coordinating Centre,

University of Hertfordshire, Hatfield, UK

Originally in: Prim Care Cardiovasc J

2010; 3(1): S6–S7

doi: 10.3132/pccj.2010.010

S Afr J Diabetes Vasc Dis 2011; 8:

161–162

Key points

• Patients with type 2 diabetes without CVD should be managed as for secondary prevention pa-tients

• Intensive LDL cholesterol lower-ing should be considered if there is evidence of reduced renal func-tion; concordance may be an is-sue if targets are not achieved

• Lifestyle changes should be en-couraged

• Add-on treatment with a fibrate will improve mixed dyslipidaemia, i.e. elevated triglycerides and low HDL cholesterol, common in these patients

Box 1) who do not follow lifestyle advice often poses

a clinical dilemma for physicians. Possible treatment

options for James are summarised in Table 1 and

discussed below.

CLINICAL OPTIONSAccording to South African guidelines (see page 155),

people with type 2 diabetes considered at high car-

diovascular risk should be managed as for second-

ary rather than primary prevention of CVD, aiming to

achieve targets of 4 mmol/l for total cholesterol and 1.8

mmol/l for LDL cholesterol, consistent with the JBS2

guidelines. In patients who fail to achieve these targets,

a number of options are recommended (see Table 1).

Intensification of cholesterol-lowering therapy

(preferably with a more effective statin) is recom-

• 62-year-old smoker (15 cigarettes/day), shift-worker

• Obese (94 kg and BMI 30 kg/m2)

• High blood pressure (148/88 mmHg)

• Total cholesterol 5.4 mmol/l, HDL cholesterol 0.90 mmol/l, LDL cholesterol 3.27 mmol/l, triglycerides 2.7 mmol/l

• HbA1c 7.4%• Moderately reduced renal function (eGFR 50 ml/

min/1.73 m2)• Taking simvastatin 40 mg, aspirin 75 mg,

metformin 2 g, enalapril 5 mg daily• UKPDS risk engine: 10-year risk of CHD 40.6%,

fatal CHD 26.4%, stroke 15.2% and fatal stroke 2.5%

Box 1: James, type 2 diabetes for six years

• Switch to a more effective statin; atorvastatin has a stronger evidence base than other higher-intensity statins

• To manage his non-LDL lipids, advise James to ex-ercise more, lose weight and eat a healthier, more balanced diet. Adding fenofibrate to statin therapy is an option

• Emphasise the importance of adherence to treat-ment

Table 1. Expert recommendations for cholesterol management


CASE STUDY 1 SA JOURNAL OF DIABETES & VASCULAR DISEASE

mended in patients with evidence of reduced renal function, as is the

case for James.

To manage his elevated triglyceride levels (2.7 mmol/l, despite statin

therapy), James should be encouraged to lose weight and eat a healthier,

more balanced diet, as recommended by guidelines. He should increase

his intake of high-fibre, low-glycaemic index sources of carbohydrate,

low-fat dairy products and oily fish, and limit foods containing saturated

and trans fatty acids. His elevated triglyceride levels might also be man-

aged by adding fenofibrate to statin therapy.

Encouraging lifestyle change is also important. In accordance with

NICE Public Health Intervention Guidance, James should be advised to

quit smoking, and offered a referral to an intensive support service. If he

is unwilling to accept this, he could be offered pharmacotherapy.

EXPERT CONSENSUSIt is important that James achieves the lipid targets recommended in

guidelines in order to reduce his cardiovascular risk. Given his irregu-

lar working hours and unhealthy lifestyle, his compliance with treatment

should be checked first as a possible reason for failure. If compliance is

an issue, this should be discussed with James. The use of a statin with a

longer half-life, such as rosuvastatin or atorvastatin, may be preferable.

These higher-intensity, longer half-life statins also provide additional LDL

cholesterol-lowering efficacy compared to simvastatin 40 mg.

James also presents with the mixed dyslipidaemic profile – elevated

triglycerides and low HDL cholesterol – typical of type 2 diabetes, which

persists despite statin therapy. Addition of fenofibrate to his statin

might be considered to manage his non-LDL lipids, based on guideline

recommendations and clinical evidence. Nicotinic acid can have an

advantageous effect on serum HDL cholesterol in addition to other lipids,

but would not be recommended for James because of possible negative

effects on his blood glucose control.

The target blood pressure for James should be < 130/80 mmHg given

that his eGFR is < 60 ml/min/1.73 m2. With his irregular working hours,

his antihypertensive medication should be changed to a once-daily ACE

inhibitor or ARB. Ramipril use is supported by findings from the Heart

Outcomes Prevention Evaluation (HOPE) study, which showed significant

reduction in CVD events and the MICRO-HOPE sub-study, which showed

reduction in overt nephropathy. Dosage should be titrated to 10 mg daily

as used in the HOPE study, with urea and electrolytes being checked

after each increase in dose.

Lifestyle advice is extremely important in this patient, and he should be

actively encouraged to improve his lipid, blood pressure and glycaemic

control.

• Consider the possibility of poor compliance, especially if the patient is not following lifestyle advice. Emphasise the importance of concordance with therapy

• Improve lipid control by switching to a longer-acting, higher-intensity sta-tin; consider adding fenofibrate for management of mixed dyslipidaemia

• Emphasise the importance of lifestyle intervention

Take-home messages: type 2 diabetes patient not achieving lipid targets

KEY GUIDANCE AND TRIALS• NICE gives specific guidance in type 2 diabetes: CG 87 (an update

of CG66), May 2009. http://www.nice.org.uk/CG87 and http://www.

nice.org.uk/CG66

• For information on smoking cessation, refer to NICE – Brief Interven-

tions and referral for smoking cessation in primary care and other

settings. http://www.nice.org.uk/nicemedia/pdf/PH001_smoking_

cessation.pdf and NICE Public Health Guidance 10. Smoking cessa-

tion services. http://guidance.nice.org.uk/PH10/NiceGuidance/pdf/

English

• The HOPE Study (Heart Outcomes Prevention Evaluation Study) showed

that ramipril significantly reduced the risk of the primary compos-

ite cardiovascular outcome (MI, stroke and cardiovascular death) by

25% (95% CI: 12–36, p = 0.0004). The MICRO-HOPE substudy also

showed reduction in overt nephropathy by 24% (95% CI: 3–40, p =

0.027). Treatment was well tolerated and most patients continued on

the 10-mg dose.



Case Study 2

Type 2 diabeTes paTienT wiTh musCle aChes on sTaTin Therapy

Presented by Dr Patrick TwomeyConsultant Chemical Pathologist (with a special interest in lipidology), Ipswich Hospital, UK

Originally in: Prim Care Cardiovasc J 2010; 3(1): S8–S10doi: 10.3132/pccj.2010.012


Key points

• All statins can cause muscle symptoms such as pain, tender-ness or weakness, with or with-out elevation in creatine kinase levels

• Hydrophilic statins, such as rosuvastatin or pravastatin, may be less likely to cause muscle symptoms

• Ezetimibe, either alone or as add-on to low-dose statin thera-py, or nicotinic acid, are options if symptoms persist in the well-controlled patient

• 56-year-old, healthy weight (70 kg, BMI 25 kg/m2)

• Good control of glycaemia (HbA1c 6.6%) and blood pres-sure (132/82 mmHg)

• Total cholesterol 5.0 mmol/l, HDL cholesterol 1.30 mmol/l, LDL cholesterol 2.88 mmol/l, triglycerides 1.8 mmol/l

• Taking simvastatin 40 mg, aspirin 75 mg, metform-in 1.5 mg daily

• Complains of generalised aches and pains, particu-larly when exercising

• CK, thyroid function and liver function tests within normal limits; eGFR 55 ml/min/1.73 m2

• UKPDS risk engine: 10-year risk of CHD 7.5%, fatal CHD 4.4%, stroke 3.8% and fatal stroke 0.5%

Box 1: Rose, type 2 diabetes for 10 years

Statin intolerance is defined as the presence of clinically significant adverse effects associated with statin therapy that are considered to

represent an unacceptable risk to the patient or that may result in compliance being compromised. All statins can cause myositis: muscle symptoms such as pain, tenderness, or weakness accompanied by creatine kinase (CK) levels > 10 times the upper limit of the normal reference range. Statins have also been implicated in the development of myalgia: muscle aches and pains not associated with any significant elevation in CK levels.

A patient with type 2 diabetes suffering unex-plained muscle aches and pains might consider dis-continuing statin treatment, but the well-established evidence base supporting statin therapy for CVD prevention underlines the importance of continuing with LDL-lowering therapy. Managing these patients, such as Rose (see Box 1), poses a dilemma to the physician. Possible treatment options are summa-rised in Table 1 and discussed below.

CLINICAL OPTIONSThere are a number of factors to be considered in the management of Rose. Her cholesterol treatment targets should be 4.0 mmol/l for total cholesterol and 2.0 mmol/l for LDL cholesterol, based on the JBS 2 and NICE guidance. However, her reported general-

If symptoms resolve after discontinuing statin therapy:

• Switch to a hydrophilic statin (e.g. rosuvastatin or pravastatin) less likely to cause muscle pain

• Re-introduce simvastatin at 10 mg and slowly up-titrate to the optimal dose that does not cause mus-cle symptoms

• Add on ezetimibe to low-dose statin therapy

• If symptoms persist, consider ezetimibe mono-therapy

Table 1. Expert recommendations for cholesterol management for Rose


CASE STUDY 2 SA JOURNAL OF DIABETES & VASCULAR DISEASE

ised muscle aches and pains should first be investigated for possible statin intolerance, as this may influence her treatment options. In this case, measurement of CK and thyroid function in the context of muscle pain, as well as liver-function tests, were all within the normal reference range. She was advised to discontinue statin therapy for one month to investigate whether her muscle aches resolved.

After checking for statin intolerance, there are three options for her management (Table 1).

South African guidelines recommend statin therapy for CVD preven-tion in patients with type 2 diabetes, so it is important to continue treat-ment. (See South African lipid guidelines on page 155.) Switching to a hydrophilic statin such as rosuvastatin or pravastatin may be less likely to cause muscle pain compared to a lipophilic statin. In one study, nearly two-thirds of patients who were intolerant to a particular statin were able to tolerate an alternative statin without side effects.

Alternatively, simvastatin could be re-introduced at a lower dose (10 mg) and slowly up-titrated to the optimal dose that does not cause muscle symptoms. Titration to target LDL cholesterol levels could also be achieved by adding ezetimibe to low-dose statin therapy, in accordance with European Society of Cardiology (ESC) guidance. If muscle symptoms persist, ezetimibe monotherapy could be considered and the patient re-ferred for ankle-brachial pressure tests for possible peripheral arterial disease.

Glycaemic control, blood pressure and BMI are all good in this patient, suggesting that she is following lifestyle advice appropriately. She is be-ing treated with low-dose aspirin, based on guideline recommendations for treatment in patients with type 2 diabetes aged over 50 years and with blood pressure below 145/90 mmHg. However, it is also important to consider whether the risks associated with aspirin therapy are justified in this patient, given that her 10-year estimated CHD risk is 7.5% and her 10-year risk for stroke is 3.8%.

EXPERT CONSENSUSA well-established body of evidence supports the benefits of CVD preven-tion including LDL cholesterol lowering with a statin in patients with type 2 diabetes. However, this case of possible statin intolerance highlights the need to consider non-statin options for lipid management.

Discussing treatment options with the patient to help her to make in-formed decisions about her therapy is clearly important, as highlighted by South African guidelines. This should involve discussion of the risks and benefits of the various treatment options, as well as the importance of concordance in achieving recommended LDL cholesterol targets and preventing CVD events, including stroke.

The importance of adherence to a healthy lifestyle, as already adopted by this patient, in CVD prevention should also be re-emphasised, sup-ported by evidence from the STENO-2 study. If, as in this case, the patient has a low risk score, this information should be communicated care-fully to avoid any misperception by the patient that she does not need cholesterol-lowering medication.

If muscle symptoms return after re-introducing a statin and are likely to influence patient compliance, non-statin treatment options should be considered. In this patient, these would involve a choice between ezetimibe, or a nicotinic acid formulation – ideally one with reduced flushing potential (i.e. in combination with laropiprant, an anti-flushing agent). Although no general recommendations for the use of nicotinic acid in type 2 diabetes patients are given in recent guidelines, this treatment may be considered for Rose as she has good glycaemic control. Nicotinic acid medicinal products have been associated with increases in fasting blood glucose levels, so the patient should be monitored closely, with adjustment of diet and/or hypoglycaemic therapy as necessary. A fibrate is not indicated as a non-statin alternative in this patient because her triglyceride levels are not sufficiently elevated (~1.8 mmol/l).

After discussing the risks and benefits of nicotinic acid, the patient might prefer re-introduction of a low dose of statin with add-on ezetimibe therapy for improved LDL cholesterol-lowering efficacy. This approach, which is recommended, may represent the preferred option in this pa-tient.

Finally, from a practical viewpoint, the physician should be aware of the risk of relying on ‘normal’ results, especially given the lack of stand-ardisation in measurement of liver function tests across different labo-ratories. Any elevation in CK needs to be considered in the context of the patient’s usual activities, which in this case include regular exercise. This underscores the need for measurement of CK before starting lipid-modifying treatment to obtain appropriate baseline levels.

• Investigate for possible statin intolerance

• Consider switching to a hydrophilic statin or add on ezetimibe to low-dose statin therapy

• If symptoms persist, consider non-statin options

Take-home messages: type 2 diabetes patient with muscle aches on a statin

SUMMING UP: TAKE-HOME MESSAGES• Lowering cholesterol to recommended targets (4 mmol/l for total

cholesterol and 1.8 mmol/l LDL cholesterol) is essential in high-risk patients, including in secondary prevention cases, prior CABG, and primary prevention in most type 2 diabetes patients

• Treatment options should be discussed with the patient, taking into account informed preference, co-morbidities, multiple drug therapy and the benefits and risks of treatment. The importance of concord-ance with therapy and lifestyle management should be emphasised

• Switching to higher-intensity statins is preferable to up-titrating sim-vastatin dosage to optimise LDL-lowering efficacy and tolerability. Add-on ezetimibe is an option if targets are not achieved

• Where there is evidence of possible statin intolerance, ezetimibe may be a useful non-statin option.



Keep and Copy SeriesPatientinformationleaflet

TaKing ConTrol oF your CholesTerol leVels

S Afr J Diabetes Vasc Dis 2011: 8: 165–166. T he first time your doctor/clinic sister tells

you that you have high cholesterol levels, it

can come as quite a shock, particularly if

you are otherwise healthy. Raised cholesterol levels

result in a greater risk of heart disease and you will

want to avoid this severe complication and hazard

to life.

High cholesterol can occur for a number of rea-

sons. Eating foods high in saturated fats, exercising

too little, being overweight or obese, smoking and

regularly drinking too much alcohol are all lifestyle

factors that can cause raised cholesterol.

Some medical conditions are also known to cause

high cholesterol. These include diabetes, hyperten-

sion, liver or kidney disease and an under-active thy-

roid gland. These are all treatable conditions.

Medicines prescribed for other reasons may also

result in high cholesterol as a side effect. Some of

these are birth-control pills, beta-blockers, some

diuretics and some antidepressants.

Risk factors for raised cholesterol levels that can-

not be treated include a family history of coronary

heart disease, stroke, hypercholesterolaemia or hy-

perlipidaemia. Men have a greater chance of having

higher blood cholesterol levels than women. Aging

and experiencing an early menopause also increase

the risk. Some ethnic groups may be more suscepti-

ble to high cholesterol levels than others.

SO WHAT CAN YOU DO TO IMPROVE THE SITUATION?The first important aspect is to realise that by chang-

ing your lifestyle, losing weight, exercising and us-

ing natural remedies such as plant stenols (special

margarines and natural over-the-counter products

such as Phytocor), you can lower your total choles-

terol level by some 2–3%. This may be enough, and

for most of us, this is a better solution than taking

medication! So, try this approach for the first three

months. Then visit your doctor/sister again and ask

that he/she redo your lipid test using the same test

as before.

Since lifestyle factors are just one of the reasons

for high cholesterol levels, sometimes changing your

lifestyle is not enough to lower these levels. If your

cholesterol levels are still raised, the doctor will ex-

plain that medication is essential. You then need to

say: ‘Tell me what my lipid levels are’. These include

total cholesterol, low-density lipoprotein cholesterol

(LDL-C); high-density lipoprotein cholesterol (HDL-C)

and triglycerides (TG).

The general idea is that your total cholesterol

must be below 5 mmol/l, the LDL-cholesterol be-

low 2.5 mmol/l, the HDL-C (the good cholesterol)

at or above 1 mmol/l and the triglycerides below 2

mmol/l. If you have had a heart attack, stroke or have

diabetes, your doctor might want to go even lower

on your LDL-C and triglycerides. Make sure he/she

explains why he/she wants to do this.

The medication he/she prescribes will consist of

one or more drugs. Most commonly the first medi-

cine will be a statin but it may also be drugs that

interfere with cholesterol uptake, such as ezetimibe

or a fibrate. You may even be given one tablet that

combines two different classes of drugs.

STATIN THERAPYThe dose of statin (a drug that blocks the enzymatic

production of cholesterol in the body) prescribed

by your doctor will depend on your cholesterol


PATIENT INFORMATION LEAFLET SA JOURNAL OF DIABETES & VASCULAR DISEASE

level. Generally, your doctor will start on a lower dose of statin, called

simvastatin (10/20 mg), raising it to 40 mg if needed. He/she will not

prescribe an 80-mg dose of simvastatin as this has been shown to be

at a disadvantage to newer statins such as atorvastatin and rosuvastatin

(the newest and most powerful statin available).

HOW WILL I KNOW IT IS WORKING?Studies have shown that statins reduce the risk of heart attacks and

strokes. For this reason, there is no need to have a routine blood test to

check your lipid levels once your doctor is satisfied that your cholesterol

levels are at the target level you and he/she have set. However, your liver

function will be tested at three and 12 months to ensure that the drug is

suiting you, and your lipid profile will be checked annually.

HOW LONG SHOULD I TAKE IT FOR?Your cholesterol level will be lowered by taking the tablets. If you stop

taking them, it will rise again. For this reason, we advise that you keep

taking the tablets as long as possible, and ideally, for life.

One exception may be if you make significant changes to your diet or

lose a lot of weight. Substantial lifestyle changes may keep on lowering

your cholesterol level without you continuing to take the medication, but

don’t make any changes to your lifestyle or medication without speaking

to your doctor/clinic sister first.

WHAT COMMON SIDE EFFECTS MIGHT I EXPECT?Side effects from statins are surprisingly rare. However, all drugs have

side effects. Even ‘dummy’ pills used in medical trials have been shown

to cause side effects in some people, so it is not always the tablet that

is to blame.

With statins, rare side effects include muscle or joint pains, lack of

energy, constipation and indigestion and you should let your doctor, nurse

or pharmacist know if these occur. It is important to remember, however,

that the likely benefits from statins are greater than the risks, certainly for

the majority of people.

WHAT IF I TAKE OTHER MEDICINES?It is important to check whether statins interact with any other medicines

the doctor has prescribed, or with over-the-counter drugs or supple-

ments. These include herbal and ‘home’ remedies.

WHAT IF I DECIDE THAT I DO NOT WANT TO TAKE THESE PILLS?Your doctor or nurse will have advised you to take these tablets because

you are likely to benefit from reducing your risk of a heart attack or

stroke. High cholesterol does not make you feel unwell so it can some-

times be difficult to understand why you should take a tablet for the rest

of your life. Nonetheless, it is worth remembering that large medical

trials have proven the benefit of these pills in reducing the risk of heart

attack or stroke.

EZETIMIBE Ezetimibe is a drug that inhibits absorption of cholesterol by the small

intestine. In South Africa, this medicine is often used in a single-tablet

combination with simvastatin. The advantage of this statin/ezetimibe sin-

gle pill is that it is associated with fewer side effects than the equivalent

statin-based cholesterol-lowering dosage. For some patients who experi-

ence muscle pains on statins, this combination is very useful.

FIBRATES (FENOFIBRATE)Fibrates, particularly fenofibrate, are added to statin therapy when cho-

lesterol targets are not reached, but mainly to lower triglyceride levels.

While there is more than one fibrate formulation available in South Africa,

the cardiovascular and microvascular protection of fenofibrate has led to

an evidence-based usage of this agent.

Fibrates lower blood triglyceride levels by reducing the liver’s produc-

tion of the carrier of the triglyceride particle (VLDL) and by speeding up

the removal of triglycerides from the blood.

Diabetic patients are frequently prescribed a combination of a statin

plus ezetimibe/fibrate.

Source: Medline Plus

It's theshell that

makes

safer.

Safety-CoatedR

81mgThe ORIGINAL low dose aspirinfor optimum cardio-protectionHp

Each tablet contains Aspirin 81mg. Reg.No.: 29/2.7/0767Pharmafrica (Pty) Ltd, 33 Hulbert Road, New Centre, Johannesburg 2001Under licence from Goldshield Pharmaceuticals Ltd. U.K.



Diabetes Educator’s Focus

oral healTh in diabeTes

Oral care is particularly important for the

patient with diabetes. Emerging research

suggests that the relationship between

serious gum disease and diabetes is two way. Dia-

betics are more susceptible to serious gum disease,

but serious gum disease may have the potential to

affect blood glucose control and contribute to the

progression of diabetes.

Good blood glucose control is key to managing

and preventing mouth problems. Poor blood glucose

control impairs the functioning of white blood cells,

necessary for defence against bacterial infections

that can occur in the mouth. The less well controlled

the blood sugar levels, the more likely oral health

problems will arise, resulting in more frequent and

more severe oral disease.

Daily brushing and flossing, regular dental check

ups and good blood glucose control are the

best defence against the oral complications of

diabetes.

The smoking diabetic patient faces an even

greater risk (20 ×) for the development of thrush

and periodontal disease. Smoking impairs blood

flow to the gums and may affect wound healing

in this area.

harmful wastes from the cells. The infection-fighting

ability of the immune system becomes impaired and

results in poor healing of oral tissue.

Gingivitis (early-stage gum disease) and periodontal

disease, a bacterial infection of the gum and bone that

hold the teeth in place, can lead to painful chewing

difficulties and even tooth loss. Plaque build up along

the gum line hardens and the gums pull away from the

teeth. Pockets of infection below the gum cause bone

loss, which may result in loosening of the teeth.

The frequent use of antibiotics in diabetes makes

the patient particularly prone to developing fungal in-

fections of the mouth and tongue. Thrush (Candida)

thrives on the high levels of sugar in the saliva, cre-

ating painful areas that may turn into ulcers. Thrush

presents as white (sometimes red) patches in the

mouth, including the palate. It is easily scraped away,

but will rapidly regrow.

THE DIABETIC PATIENT FACES A HIGHER RISK OF A NUMBER OF ORAL CONDITIONS Xerostomia (dry mouth) is a common diabetes-relat-

ed condition that may be a side effect of medicines

taken. A dry mouth may make the patient more sus-

ceptible to cavity formation, as there is less saliva

to wash away bacteria and the acids they produce.

Xerostomia can lead to further discomfort; the devel-

opment of ulcers and tooth decay, and infections of

the gums and salivary glands. Simple interventions

such as drinking more fluids and chewing sugar-free

gum may help keep the saliva flowing.

Diabetic patients are at increased risk of gum in-

flammation. A common complication of diabetes is

the thickening of blood vessels, affecting blood flow

and slowing the inflow of nutrients to and removal of

DENTIST ALERT: WARNING SIGNS FOR THE PATIENT TO ACT ONOften gum disease is painless. The patient may not

even realise he/she has gum disease until some se-

rious damage has been incurred, so regular visits to

the dentist are of great importance. It is essential to

pay special attention to any changes in oral health. If

one or more of the following problems present, there

may be tooth damage and/or gum disease:

pain in the mouth/sinus area that does not go •

away

white or red patches on the gums, tongue, •

cheeks or roof of the mouth

S Afr J Diabetes Vasc Dis 2011: 8: 167–168.


DIABETES EDUCATOR’S FOCUS SA JOURNAL OF DIABETES & VASCULAR DISEASE

red, sore, swollen gums•

bleeding gums when brushing or flossing. This is not normal. Even if •

the gums don’t hurt, this must still be checked

pus between the teeth and gums•

gums pulling away from the teeth so that they look long; parts of the •

root may show

loose or sensitive teeth•

bad breath•

a bite that feels different•

dentures/false teeth that do not fit well, or have stopped fitting well•

teeth that hurt when eating something cold/hot/sweet or when •

chewing

dark spots or holes in the teeth.•

CONSIDERATIONS WHEN VISITING THE DENTISTA multidisciplinary health-team approach provides comprehensive care

for people with diabetes. Each member of the team contributes particu-

lar skills and experience. Collaboration and communication are essential

components of a team-care approach, facilitating co-ordination of care.

A visit to the dentist may require the involvement of the diabetes doctor;

and the diabetes doctor may require information from the dentist. There

are some useful points to consider when visiting the dentist:

Acute infections (abscesses) should be treated immediately. Post-•

pone non-emergency dental-care procedures if the blood sugar level

is not well controlled. Should orthodontic appliances cut the gums or

cheeks, immediately consult with the orthodontist.

Keep the blood sugar levels as close to normal as possible; it is best •

to eat before the dental appointment. If on insulin, a morning appoint-

ment after a normal breakfast is best.

Tell the dentist about your diabetes status at each visit and have a list •

of the names and dosages of all medications currently being taken.

The dentist needs to know if other medications will interact with any

prescriptions that may be given.

See the diabetes doctor before scheduling treatment for periodontal •

disease. If oral surgery is planned, the doctor or dentist will advise on

any pre-surgical antibiotics required, changes to meal schedules, or

changes to timing and dosage of insulin.

The post-treatment instructions of the dentist must be closely fol-•

lowed. If the mouth is sore after dental work, the patient may not be

able to eat or chew for several hours or days. Seek guidance from

the doctor on how to adjust the normal routine while the mouth is

healing (remember this may be prolonged in the diabetic patient).

Most importantly, find out what changes are required with food, drink

and diabetes medication. Also find out how often blood glucose levels

should be checked.

Glenda Hardy

Day-to-day oral care tips

Brush your teeth after every meal, using a soft-bristled tooth-•

brush. Turn the bristles against the gum line and brush gently.

Use small circular motions. Brush the front, back and top of each

tooth. Remember to brush the rough surface of the tongue to

remove germs. Replace the toothbrush when the bristles are worn

or bent, about every three to four months.

Prevent plaque build up by using dental floss at least once a day. •

Floss reaches places the toothbrush can’t. Using a sawing motion,

gently bring floss between the teeth, scraping from bottom to top

several times. Never snap the floss into the gum.

If you have dentures, remove and clean daily.•

If smoking, talk to the doctor about ways to quit. •

Have your teeth and gums cleaned and checked by a dentist twice •

a year, although the dentist may specifically recommend closer

intervals.

Make an appointment with the dentist if you have red, sore or •

bleeding gums, or gums that are pulling away from the teeth. Also

schedule appointments for a sore tooth that could be infected, or

pain from dentures.



‘walKing The walK’ To a greaTer undersTanding oF diabeTes

Diabetes nurse educator (DNE) Christine

Swart believes in ‘walking the walk’ to

a deeper understanding and control of

diabetes alongside her patients, every step of the

way. She is uniquely placed to do this. An insulin-

dependent diabetic herself for more than 20 years,

she’s living proof that it’s possible to have diabetes

and still lead a normal, healthy life. ‘I believe that

ultimately diabetics are people just like everyone

else with the same general concerns and challenges.

Managing their diabetes is just one additional aspect

of their lives and not something that defines them’,

she says.

Based at Netcare Kuils River Hospital in the north-

ern suburbs of Cape Town, Christine works with

three physicians and four gynaecologists, providing

diabetes education to all patients admitted to the

hospital’s various wards. The population she serves

is diverse, ranging from the wealthy to the disadvan-

taged, but she is committed to giving a good-quality

service to all and to working around any constraints

related to funding. In addition she runs a monthly

support group that addresses topics identified by

the patients themselves. ‘Once a year, this takes the

form of a dinner at an outside venue – usually with

a dietician present. It provides a good opportunity to

advise on correct eating choices’, she says.

A registered nurse with a background in primary

care and community health nursing, Christine first

became involved in diabetes when she worked at

Netcare Park Lane Clinic in Johannesburg, counsel-

ling pregnant women with gestational diabetes. On

her return to Cape Town, she became aware of how

many diabetics received inadequate counselling and

the prescriptive, unempathetic way they were often

treated. She has been a DNE since 1997 and in her

current position since 2002.

‘Most people don’t really understand what hap-

pens in the body when you have diabetes’, she says.

‘There are many myths and misconceptions that

need to be addressed. When a patient comes to me

for the first time, I start by assessing how much they

know and understand, and sift out the correct infor-

mation from the nonsense. I then give them a basic

course in physiology, using models and pictures of

the body so that they become familiar with the vari-

ous organs and their location. I also have a model

hamburger that I dissect in front of them as I explain

how eating it affects a diabetic versus how it affects

someone without the condition. I tell them how that

extra glucose affects the various organs and the po-

tential damage it can do.’

Christine emphasises that it’s important to keep

things simple and avoid information overload. To this

end, she often educates incrementally in ‘manage-

able portions’ over successive patient visits and

uses tests to assess that patients understand what

they’ve been told. ‘I make them aware that the dis-

ease will progress and that the pancreas will secrete

less insulin over time. This does mean that they will

probably need to change their therapy in the years

ahead.’

Once patients understand the condition, the next

step is to educate them around its treatment. This

also takes time, especially when it comes to insu-

lin therapy, which Christine feels requires at least a

90-minute to two-hour conversation. In addition, all

patient conversations are individualised and ‘tailor-

Diabetes Personality

S Afr J Diabetes Vasc Dis 2011: 8: 169–170.

‘Most people don’t really understand what happens in the body when you have diabetes’


DIABETES PERSONALITY SA JOURNAL OF DIABETES & VASCULAR DISEASE

made’, as Christine believes that each patient is different and one can-

not use a standardised approach. ‘I can’t stress enough that ensuring

compliance takes time and requires ongoing support and motivation. The

support of a multidisciplinary team is essential to ensure this.’

An important aspect of the conversation on treatment is to dispel the

very human desire for a ‘quick fix’ and to ensure that patients make

peace with diabetes being a lifelong, chronic condition. ‘Acceptance

does not come instantaneously and it’s a long process.’ Christine ex-

presses concern about untested products available over the counter

that make claims to ‘cure’ diabetes. ‘When asked about these prod-

ucts, which usually also have the attraction of being cheaper than pre-

scription medication, I ask the patient what he/she really knows, what

research he/she has read, how does this product claim to work and

how do its claims align with what I’ve told him/her about diabetes and

its management. I never lose sight of how powerful marketing is in this

context’, she says.

Another particular challenge for Christine is counselling male diabetics

with erectile dysfunction. ‘It’s become easier over time but it was initially

very difficult for me, as an unmarried woman, to broach the subject. But

if I don’t ask, I cannot help. However, nowadays I explain exactly what

happens in the body and discuss treatment options before referring them

back to their doctor for medication.’

Like other DNEs, Christine’s greatest reward lies in seeing patients

become compliant and gain control over their condition. ‘One woman in

my support group – I’ll call her Mrs J – originally came to me in 2005.

She weighed 80 kg and was on oral antidiabetic medication. Today she

weighs 62 kg and is off the drugs, controlling her diabetes through a

healthy diet and regular exercise. She’s extremely motivated and even

accompanied me to the AGM of Diabetes SA this year. I’m so proud of her

and her commitment to her way of life. She’s also a great role model for

other diabetics and is only too happy to tell her own success story when

given the opportunity at support group meetings.’

Peter Wagenaar, Gauteng correspondent

Christine helps a young colleague get to grips with caring for patients with diabetes.


SA JOURNAL OF DIABETES & VASCULAR DISEASE JOURNAL UPDATE

Journal UpdateSouthern African contributions

The recent UN summit on non-commu-nicable diseases (NCDs) highlighted the

emerging burden of disease in Africa. Particu-lar emphasis was paid to preventable lifestyle choices as risk factors for NCDs, including tobacco use, unhealthy diet, lack of physi-cal activity and alcohol abuse. It appears that the negative consequences of a drift in Africa towards a Western lifestyle is being com-pounded by a genetic predisposition towards the development of NCDs. These factors and other therapeutic issues are discussed in this update of relevant articles on southern Africa from the world literature.

LIFESTYLE Lifestyle and conventional risk fac-tors responsible for excess burden of sub-clinical vascular disease in black Africans compared to Cauca-sians in South AfricaThere is an emerging burden of cardiovascular disease among urban black Africans in South Africa. This rise has been largely explained by the transition from traditional African life-styles to more westernised behaviour: more sedentary routines, smoking and unhealthy diets, including an excess intake of saturated fats, highly processed foods and alcohol.

Existing data has generally shown higher levels of sub-clinical vascular disease in par-ticipants from lower socio-economic back-grounds and in blacks. It is difficult to estimate the true contribution of health behaviour from self-reported measures alone as these suffer from considerable reporting bias. From three health behaviours studied in this article, alcohol was the most important risk factor for vascular disease. Low physical activity was associated with a number of other cardio-vascular disease (CVD) risk factors, including body mass index (BMI), triglycerides (TGs), blood pressure and C-reactive protein (CRP).

The aim of the study was to examine the role of objectively assesed health behaviours in explaining the excess burden of sub-clinical vascular disease seen in urban black Africans compared to Caucasians. The black (192) and Caucasian (206) participants were well matched for age and gender distribution.

In general, the blacks demonstrated more risk factors, including higher ambulatory

systolic and diastolic blood presure, TGs, BMI, CRP and a higher prevalence of the metabolic syndrome. In addition, blacks were less physi-cally active and more likely to smoke. The black sample reported lower use of alcohol, although both black alcohol users and non-users demonstrated higher levels of gamma glutamyl transferase than Caucasians. This might suggest the presence of alcohol-in-duced liver damage from previous alcohol abuse in blacks who reported non-drinking status. Alternatively it may reflect a greater prevalence of non-alcoholic fatty liver disease in the blacks.

Results further revealed a higher preva-lence of hypertension in the black sample. Black Africans demonstrated higher mean carotid intima–media thickness (mCIMT) compared with Caucasians, although the difference was considerably attenuated after adjustment for conventional and behavioural risk factors. This attenuation suggests that the emerging burden of CVD among urban black Africans in South Africa is largely caused by modifiable factors.

Key take-home message: Higher ambu-latory systolic and diastolic blood pressure, and raised triglycerides and body mass index are the major factors driving vascular disease in black South Africans.

Source: Hamer M, Malan L, et al. Conventional and behavioural risk factors explain differences in sub-clinical vascular disease between black and Caucasian South Africans: The SABPA study. Atherosclerosis 2011; 215: 237–242. DOI: 10/1016/j.atherosclerosis.2010.12.015.

South African black smokers demon-strate greater cardiovascular dys-function than Caucasian smokers Globally, the prevalence of smoking-related CVD is higher in Africans than Caucasians. Many studies have reported the effect of smok-ing on the metabolic syndrome, and together they cause dyslipidaemia, increased CRP levels and endothelial dysfunction. Smokers are therefore characterised by high serum TG and low-density lipoprotein cholesterol (LDL-C), with significantly lower high-density lipopro-tein cholesterol (HDL-C) than non-smokers.

Nicotine intake leads to increased blood pressure and decreased oxygen-carrying

capacity of the blood, which may in turn cause ischaemia and hypoxia. This stimulates increased red blood cell production, contrib-uting to increased viscosity and consequently inflammatory and coagulatory processes. Inflammation and coagulation are associated with atherosclerosis and cornonary heart disease. All of these factors contribute nega-tively to increased risk for CVD.

This study aimed to determine the associ-ation between smoking and measurements of vascular function in African and Cauca-sian people of South Africa. Anthropometric and cardiovascular variables, serum creati-nine and CRP levels were measured.

African smokers had significantly increased arterial stiffness, which was not found in Cau-casian smokers. Africans also showed more associations between smoking and cardio-vascular dysfunction than the Caucasians. A high degree of urbanisation among Africans, coupled with higher smoking prevalence might be to blame for the high prevalence of CVD in the African population.

Key take-home message: Smoking results in more vascular damage in black compared to white South Africans.

Source: Zatu MC, Van Rooyen JM, Schutte AE. Smoking and vascular dysfunction in Africans and Caucasians from South Africa. Cardiovasc J Afr 2011; 22(1): 18–24.

Xylitol a better sweetener for the diabetic patient Chronic consumption or overconsumption of refined sugar may cause severe physio-logical and clinical problems such as over-weight, obesity, diabetes and other diseases related to the metabolic syndrome. As a result, sugar substitutes are gaining popular-ity in the market, several of which have been found to have mild to severe side effects.

Studies have pointed to the carcinogenic effects of saccharin in humans; others have shown aspartame to have significant effects in causing gastric, pancreatic and endome-trial cancers and migraines. Aspartame has also been reported to be responsible for lym-phomas, leukaemias, cancers of the bladder and brain, chronic fatigue syndrome, Parkin-son’s and Alzheimer’s disease, multiple scle-rosis, autism and systemic lupus.


JOURNAL UPDATE SA JOURNAL OF DIABETES & VASCULAR DISEASE

Of several sugar alcohols widely used as sugar substitutes, xylitol has been considered a safer sweetener, lacking the gastrointesti-nal side effects of the other sugar alcohols. Numerous studies have confirmed the effect of xylitol in the prevention of dental caries, plaque and oral biofilm production. The effects of xylitol on glycaemic control has also been reported. Compared with sucrose, xylitol has similar sweetness but relatively lower caloric value. Xylitol has a significantly lower glycaemic index (13) compared with sucrose (65), with the potential for reduction of diabetic hyperglycaemia.

The overall antidiabetic effects of xylitol as a sugar replacement on diabetes-associated parameters have not yet been investigated. Data from this University of KwaZulu/Natal Department of Biochemistry study suggests that xylitol not only reduces the blood glucose concentration but also significantly improves the glucose tolerance level compared with sucrose in non-diabetic rats.

Seventeen Sprague-Dawley rats were ran-domly divided into three groups, supplied for three weeks with drinking water ad libitum (control group), 10% sucrose solution (sucrose group) or 10% xylitol solution (xylitol group), respectively. Between the sucrose and xylitol groups, food intake was not significantly dif-ferent, but drink intake and body weight were signifcantly increased in the sucrose group.

Blood glucose data suggested that xylitol could maintain both the non-fasting and fast-ing blood glucose levels in a physiologically safer and more stable condition compared with sucrose. The significantly better glucose tolerance ability of the xylitol group confirmed that it has better effects in blood glucose and diabetes management compared with sucrose. The xylitol group also had signifi-cantly higher liver glycogen concentrations.

Key take-home message: Xylitol can be a better sweetener than sucrose to maintain diabetes-related parameters at a physiologi-cally safer and more stable condition.

Source: Shahidul Islam M. Effects of xylitol as a sugar substitute on diabetes-related parameters in nondiabetic rats. J Medicinal Food 2011; 14(5), 505-511. DOI: 10.1089/jmf.2010.0015.

GENETIC STUDIES Increased obesity-related insulin resistance in black South African women has genetic basis Adipogenesis is controlled by a sequential activation of transcription factors. Peroxisome proliferator-activated receptor γ (PPARγ) and

CCAAT/enhancer-binding protein α (C/EBPα) function with other adipogenic transcription factors to regulate the expression of lipogenic genes. The adipogenic capacity of subcu-taneous adipose tissue (SAT) has been pro-posed as a potential mechanism underlying the link between adiposity and insulin resist-ance. Reduced adipogenic capacity of SAT is typically associated with increased adipose cell size, apoptosis, inflammation, reduced vascu-larisation and insulin signalling within adipose tissue, and peripheral insulin resistance.

Despite a high prevalence of insulin resist-ance, black South African women have less visceral adipose tissue (VAT) and more peripheral (gluteal–femoral) SAT than their white counterparts. Although increased VAT is considered a major determinant of insu-lin resistance, peripheral SAT deposition has been shown to be protective, being inversely associated with fasting insulin levels in over-weight and obese pre-menopausal white women. The mechanisms underlying this apparent paradox are unkown.

The authors hypothesised that a reduc-tion in the expression of lipogenic genes may be associated with insulin resistance in black South African women. This study sought to measure expression of the genes involved in adipogenesis and lipogenesis in abdominal VAT and gluteal SAT depots and determine their relationships with insulin sensitivity in normal-weight and obese black and white South African women.

The black and white women were well matched for percentage of body fat and waist circumference, whereas obese black women had less VAT and more superficial SAT (SSAT) than white women, but similar deep SAT (DSAT). Obese black women had greater gynoid fat mass. Fasting glucose levels were not different between ethnic groups, but black women had higher fasting insulin levels than white women. Circulating adiponectin levels did not differ by ethnicity, nor did aver-age abdominal and gluteal adipocyte size.

Novel findings of the study were that the expression of PPARγ and PPARγ-responsive genes were down-regulated to a greater extent with obesity in black compared with white women. Furthermore, expression of these genes, mainly in the gluteal and DSAT depots, was associated with insulin sensitiv-ity in black but not white women. An ethnic-specific adaptation is suggested from the observation that expression of PPARγ and PPARγ-responsive genes was down-regulated to a greater extent with obesity in black com-pared with white women. The expression of the major adipogenic transcription factors and PPARγ-responsive genes was correlated

with insulin sensitivity in black but not white women. These gene associations with insulin sensitivity were significant only in the gluteal and, to a lesser extent, the DSAT depot.

Novel findings of this study indicated that gynoid fat mass was negatively correlated with insulin sensitivity in black but not white women, contrasting with the prevailing hypothesis that peripheral (gluteal–femoral) SAT deposition is protective.The findings of this study add to the weight of evidence refut-ing the hypothesis that black women display healthy obesity due to their greater periph-eral fat distribution, but instead suggest that obesity in black South African women impairs gluteal SAT adipogenesis and stor-age, potentially leading to insulin resistance and an increased risk of type 2 diabetes.

Key take-home message: Gluteal fat depositon in black women is related to insu-lin resistance, while visceral fat depostion in white women is the determinant of risk of type 2 diabetes.

Source: Goedecke JH, Evans J, et al. Reduced gluteal expression of adipogenic and lipogenic genes in black South African women is associated with obesity-related insulin resistance. J Clin Endocrinol Metab 2011; 96(12). DOI: 10.1210/jc.2011-1576.

EVIDENCE FOR CLINICAL PRACTICE Simple anthropometric measures suitable for determination of meta-bolic risk – a South African studyCentral obesity, specifically the accumula-tion of VAT, is linked to the development of several metabolic diseases, including hyper-tension, dyslipidaemia and insulin resistance. Waist circumference (WC) is used as a proxy measure for VAT; however, ethnic differences exist in the relationship between WC and VAT. Few studies have looked at the ability of central obesity measures to identify metabolic risk factors in southern African populations.

Recent studies in Europeans and Asians have shown that waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) have a greater ability than WC alone to identify patients with hypertension, dyslipidaemia and type 2 diabetes. Black South African women are on average shorter and have more periph-eral fat than white South African women. With increasing WC, black women accumu-late less VAT than white women, yet black women are more insulin resistant and para-doxically, present with lower TG and total cholesterol (TC) levels than white women. Similarly to WC and VAT, the ethnic-specific


SA JOURNAL OF DIABETES & VASCULAR DISEASE JOURNAL UPDATE

associations between WHtR and WHR with known metabolic risk factors remain to be explored in a South African population.

The present study compared the diag-nostic ability (sensitivity and specificity) of obesity measures (WC, WHtR, WHR and VAT) to identify black and white South Afri-can women with or without elevated blood pressure, dylipdaemia and insulin resistance; and to identify thresholds of obesity meas-ures that best identify risk in these women.

Apparently healthy, pre-menopausal South African women (241 black and 188 white) were assessed on basic anthropo-metric measurements and blood pressure. Blood sampling after an overnight fast determined plasma glucose, serum insulin, TC, HDL cholesterol and TG concentrations. Insulin resistance was calculated from fast-ing glucose and insulin levels.

There were no ethnic differences in body weight; however, the white women were significantly taller and had a lower BMI and WHtR than the black women. There were no ethnic differences in WC or WHR; although black women had less VAT than white women. For both black and white women there were no differences in blood pressure, and fasting glucose levels were within normal ranges. The white women had higher mean fasting glucose and lower fasting insulin levels than black women. White women had significantly higher TG, TC and HDL-C levels.

All measures of central obesity were found to be better indicators of metabolic risk in white compared to black South Afri-can women. These findings suggest that factors other than body composition, such as inflammation or environmental factors, contribute to increased metabolic disease in black women.

Another important finding was the sig-nificant differences in the diagnostic ability between VAT and anthropometric measures for identifying metabolic risk thresholds. It was found that WC was better than VAT for identifying black and white women with insulin resistance. Conversely, VAT was significantly better than WC for identify-ing elevated TG levels in white women and elevated blood pressure in black women. WC and VAT thresholds were lower in black compared to white South African women.

Considering WC and WHtR can be used to identify equivalent metabolic risk, and given the high cost and risks of radiation exposure associated with CT scans, it may be more clinically applicable to use these simple anthropometric measures over VAT for identifying metabolic risk variables.

Key take-home message: Simple anthro-pometric measures of WC, WHtR and WHR for determining metabolic and subsequent risk of diabetes are not as useful in black as in white South African women.

Source: Evans J, Micklesfield L, et al. Diagnostic ability of obesity measures to identify metabolic risk factors in South African women. Metabol Syndr Relat Dis 2011; 9(5): 350–360. DOI: 10.1089,met.2011.0034.

Mild symptomatic hypoglycae-mia does not adversely impact on beliefs about diabetes or health status over the long term Improved glycaemic control is required to minimise long-term complications of type 2 diabetes but carries the risk of hypoglycae-mia. Periods of moderate to severe hypogly-caemia and accompanying symptoms (sweating, palpitations, tremor, cognitive impairments, behavioural changes and coma) are distressing and may lead to changes in the way patients manage and think about their diabetes. Reports on the impact of mild hypoglycaemia are sparse, resulting in this study, with contributions from the Division of Endocrinology and Metabolism of the Uni-versity of the Witwatersrand.

Beliefs about illness may unfavourably change in response to mild hypoglycaemia in ways modified by external social fac-tors, education and experience. Collectively, these may influence self-care behaviour and adherence to medical regimen. Self moni-toring of blood glucose has the potential to confirm or refute subjective feelings of hypoglycaemia, as well as identify asympto-matic episodes of low blood glucose.

The aim of this study was to evaluate the association betweeen experience of mild hypoglycaemia and changes in beliefs about diabetes, self-reported well-being, health status and health behaviours over a period of 12 months.

The study randomly allocated 453 well-controlled, non-insulin dependant type 2 diabetes patients into one of three inter-ventions: (1) standardised care with three-monthly HbA1c measurements; (2) use of a blood glucose meter with minimal educa-tion or training and with clinician interpreta-tion of results; and (3) use of blood glucose meter with extensive education and training in self interpretation and application of the results to diet, physical activity and medica-tion adherence. Self-reported questionnaires assessing beliefs about diabetes, well-being, health status and health behaviour were

collected at baseline and one year.Experience of grade 1 hypoglycaemia (self

reported with no accompanying symptoms) was associated with a small increase in self-reported personal control over diabetes, but no other significant changes in beliefs about diabetes or self monitoring of blood glucose were identified. There was no evidence of long-term adverse impact on health status from the experience of mild, symptomatic hypoglycaemia. Previous studies have sug-gested a much larger impact of hypoglycaemia on quality of life than identified in this study. This study shows neither a significant asso-ciation between health status and reported experience of hypoglycaemia, nor changes in experience of hypoglycaemia over time.

Regular monitoring with subsequent regulation of lifestyle and medication may add to a sense of personal involvement and responsibility. However, those experiencing symptoms of hypoglycaemia did not share the same changes in personal control. The wider benefits of increased perceptions of personal control in supporting self manage-ment of diabetes need further evaluation.

Key take-home message: There is no evi-dence of a long-term adverse impact on beliefs about diabetes or health status in those patients experiencing mild sympto-matic hypoglycaemia when self monitoring blood glucose.

Source: Malanda UL, Bot SD, et al. Experience of hypo-glycaemia is associated with changes in beliefs about diabetes in patients with type 2 diabetes. DIABETICMedicine 2011. DOI: 10.1111/j.1464-5491.2011.03340.x.

DRUGS AND THERAPEUTIC REGIMENS Addition of alogliptin to metformin and pioglitazone effective for inad-equate glycaemic control in type 2 diabetesTreatment goals of type 2 diabetes aim to achieve and maintain glycaemic control to mitigate the risk of microvascular and mac-rovascular complications. Dual oral therapy with metformin and pioglitazone is a well-es-tablished treatment option for patients with type 2 diabetes. Metformin lowers blood glu-cose, primarily by increasing hepatic insulin sensitivity. Pioglitazone increases peripheral and hepatic insulin sensitivity and potentially preserves β-cell function.

Largely due to progressive decline of β-cell function, most patients initially achieving treatment goals eventually experience a dete-


JOURNAL UPDATE SA JOURNAL OF DIABETES & VASCULAR DISEASE

rioration of glycaemic control. Such second-ary treatment failure necessitates escalation of drug doses or the use of a combination of drugs with complementary mechanisms of action to maintain glycaemic control over time. Current treatment guidelines indicate that patients with inadequate glycaemic con-trol may benefit from the addition of a third oral antidiabetic drug before initiating insulin therapy.

Dipeptidylpeptidase-4 (DPP-4) inhibitors inhibit the degradation of incretin hormones, glucagon-like peptide-1 and glucose-de-pendent insulinotropic polypeptide, thereby increasing insulin secretion and decreasing glucagon secretion after meals. These drugs may also improve β-cell function. Given the distinct but complementary mechanisms of action of alogliptin (DPP-4 inhibitor), met-formin and pioglitazone, triple oral therapy with these drugs has the potential to address both insulin resistance and Islet dysfunction. South Africa’s Helderberg Diabetes and Med-ical Centre has made a contribution to the study of efficacy and safety of triple oral ther-apy in the diabetic patient with inadequate glycaemic control.

The aim of this study was to assess the efficacy and safety of adding alogliptin 25 mg (triple oral therapy) versus uptitrating pioglitazone from 30 to 45 mg for 52 weeks in type 2 diabetes patients with inadequate glycaemic control on metformin (≥ 1 500 mg or maximum tolerated dose) and pioglita-zone 30 mg.

Triple oral therapy in patients with inad-equate glycaemic control provided clinically relevant and superior improvemnt in A1c com-pared with uptitrating pioglitazone, without increasing safety or tolerability concerns. The glycaemic benefits of triple therapy were seen as early as week four and main-tained throughout the 52-week period. Clini-cally relevant improvements were observed regardless of age, gender, ethnicity, race and baseline BMI.

Key take-home message: Adding aloglip-tin to an existing metformin–pioglitazone regimen provides superior glycaemic control and potentially improves β-cell function with no clinically important differences in safety, compared to uptitrating pioglitazone.

Source: Bosi E, Ellis GC, et al. Alogliptin as a third oral antidiabetic drug in patients with type 2 diabetes and inadequate glycemic control on metformin and pioglitazone: a 52-week, randomized, double-blind, active-controlled, parallel-group study. Diabetes, Obesity Metabol 2011; (in press). DOI: 10.1111/j.1463-1326.2011.01463.x.

Ultra-long-acting insulin degludec provides comparable glycaemic con-trol to daily insulin glargine without additional adverse events Despite the availability of many therapies, many people with diabetes are unable to reach guideline-recommended rates of glycosylated haemoglobin (HbA1c). Insulin degludec is an ultra-long-acting basal insu-lin analogue in clinical development. Phar-macokinetic properties of insulin degludec result in an ultra-long-action profile, making possible new applications of alternate-day or three-times weekly injection of this insu-lin. This can potentially help with accept-ance and early initiation of insulin therapy for some people with type 2 diabetes.

This clinical proof-of-concept trial aimed to assess the efficacy and safety of insulin degludec once a day or three times a week, compared with insulin glargine once a day in combination with metformin. The study sub-jects were insulin-naïve type 2 diabetics who were inadequately controlled on oral antidiabetic drugs. Participants were randomly allocated to receive (1) insulin degludec (900 nmol/ml) three times a week, or (2) insulin degludec (600 nmol/ml or 900 nmol/ml) once a day, or (3) insulin glargine (600 nmol/ml) once a day; all in combination with metformin.

Insulin degludec provided once a day or three times a week as add-on to metformin did not differ from insulin glargine in terms of glycaemic control. There were no appar-ent treatment-specific patterns or clustering of adverse events.

Source: Zinman B, Fulcher G, et al. Insulin degludec, an ultra-long-acting basal insulin, once a day or three times a week versus insulin glargine once a day in patients with type 2 diabetes: a 16-week, randomised, open-label, phase 2 trial. Lancet 2011; 377: 924–931. DOI: 10.1016/S0140-6736(10)62305-7.

Benefits of fibrates in reducing cardiovascular events for type 2 diabetic patients questioned Lowering the concentration of LDL choles-terol with statins substantially reduces the rate of cardiovascular events among patients with underlying CVD or other risk factors. Yet a substantial risk persists, suggesting that additional lipid-modifying interventions may be needed.

High TG levels and low levels of HDL cholesterol independently correlate with increased cardiovascular risk. There remains considerable controversy over the clinical efficacy of fibrates in overall cardiovascular

benefit. Fenofibrate has been approved for use in reducing LDL cholesterol, TG, total cho-lesterol and apolipoprotein B levels; as well as increasing HDL cholesterol levels in patients with primary hypercholesterolaemia or mixed dyslipidaemia. Fenofibric acid (the active ingredient of fenofibrate) is the only fibrate approved for use with a statin for reducing TG levels and raising HDL cholesterol levels in patients with mixed dyslipidaemia and cor-onary heart disease or those who have equiva-lent risk levels and are receiving optimal statin therapy. To date, there is no data on direct clinical outcomes to support this indication.

The ACCORD-Lipid substudy was designed to determine whether combination therapy with a statin plus fenofibrate would reduce the risk of cardiovascular events, compared with statin monotherapy. After a follow-up of almost five years, fenofibrate plus simvas-tatin had not significantly decreased the rate of the primary outcome of fatal cardiovascu-lar events, non-fatal myocardial infarction or non-fatal stroke, compared with simvasta-tin alone. However, a sub-group analysis of patients with baseline TG levels above 204 mg/dl and HDL cholesterol levels below 34 mg/dl showed a 31% reduction in the rate of primary outcome.

The question of the appropriate way to handle the approved indication for fenofi-bric acid for co-administration with a statin is controversial. The ambiguity for physicians who must make individualised decisions for patients needs to be removed. It is suggested that until sufficient evidence emerges, physi-cians prescribing combination statin–fibrate therapy should selectively target high-risk patients only after optimal control of LDL cholesterol has been achieved with statin therapy.

A properly designed trial is warranted to test the hypothesis that adding fenofibric acid to statin therapy significantly reduces the risk of cardiovascular events among high-risk patients who have reached their LDL cho-lesterol goal with a statin but have residual mixed dyslipidaemia.

Key take-home message: Fenofibrates work to lower cardiovascular risk in patients with TG levels raised above 2.3 mmol/l and HDL cholesterol levels below 1.0 mmol/l. Other type 2 diabetes patients do not show benefit from fenofibrate addition.

Source: Goldfine AB, Kaul S, et al. Fibrates in the treatment of dyslipidemias – time for a reassessment. New Engl J Med 2011; 365(6): 481–484.

Glenda Hardy


SA JOURNAL OF DIABETES & VASCULAR DISEASE REPORT

Controversies at ESC 2011: Dietary approaches for lipid assessment

At this year’s Congress of the European Society of Cardiology (ESC), 27–31

August in Paris, France, experts debated a number of controversial issues. A key ses-sion was the debate on dietary approaches for lipid assessment, chaired by Prof Rory Collins, Oxford, UK and Dr Mikael Rabaeus, Clarens-Montreux, Switzerland.

From: Br J Prim Care Nursing 2011, published online.

S Afr J Diabetes Vasc Dis 2011; 8 : 175–177.

Building on his argument, Prof Bruckert showed that there is overwhelming evi-dence from population studies, clinical out-comes trials and genetic studies to confirm the cardiovascular benefits of a long-term 10% reduction in LDL cholesterol.3,4 In a meta-analysis of 58 dietary and drug trials involving nearly 15 000 subjects, long-term reduction in LDL cholesterol of 1.8 mmol/l (∼70 mg/dl) reduced the risk of ischaemic heart disease by about 60%.3 Therefore, by extrapolation, he implied that lowering of LDL cholesterol levels by ∼10% with dietary plant sterol supplementation is likely to be useful in preventing CVD.

In the second part of his presentation, Prof Bruckert focused on issues relating to the risk versus benefit of plant sterol supple-mentation. He emphasised that the safety dossiers for phytosterol-supplemented products have been extensively reviewed by numerous regulatory agencies, including the US Food and Drug Administration. Over-viewing the data, he concluded that there was no consistent evidence of accumulation of plant sterols in tissues, oestrogenic effects or effects on the gut morphology or physiol-ogy. Instead, the data suggested that dietary phytosterol supplementation may be associ-ated with possible anti-atherogenic effects, based on three key lines of evidence. • First, recent studies in large numbers of

patients using appropriate adjustment of confounders showed no associa-tion between increased plasma levels of plant sterols and risk for ischaemic heart disease.5-7 For example, in the Longitudi-nal Aging Study Amsterdam, high plasma levels of sitosterol, a marker of plant sterols, were associated with a markedly reduced risk for coronary heart disease (CHD), suggesting that plant sterols might have protective anti-atherogenic effects.6

• Second, extensive experimental data consistently showed beneficial effects on stabilisation or regression of atheroscle-rosis.8

• Third, a systematic meta-analysis includ-ing data from 17 studies in 11 182 subjects did not indicate an association between serum levels of plant sterols and increased risk of CVD.9 In summing up his case, Prof Bruckert

emphasised that phytosterol-supplemented

foods have been recognised as effective and safe in almost all countries.

Dr Oliver Weingärtner, University Hospi-tal of Saarland, Homburg at Saar, Germany argued the case against the motion. He sug-gested the need for caution in extrapolating that lowering of LDL cholesterol with dietary plant sterol supplementation translates to reduction in CVD risk. To highlight his point, he referred to the ILLUMINATE trial with the cholesteryl ester transfer protein inhibitor torcetrapib.10 Although effective in raising high-density lipoprotein cholesterol and low-ering LDL cholesterol, torcetrapib was also associated with an increase in risk for major cardiovascular events. Additional research suggested that this adverse effect was most likely attributable to off-target pharmaco-logical effects on the adrenals, resulting in hyperaldosteronism and hypertension.11

In a key point, Dr Weingärtner highlighted the fact that while the human body has very efficient means of eliminating sterols in a normal diet, plant sterol supplementation has been shown to more than double serum sterol levels. The biological significance of this effect has been the subject of much debate.

Dr Weingärtner overviewed data from two studies. In one small study, dietary sup-plementation with plant sterols increased plasma sterol levels and sterol concentra-tions in aortic valve tissue in patients with aortic stenosis.12 Another study showed that common genetic variants at the ATP-binding cassette hemitransporter ABCG8 and ABO blood group, gene loci were associated with increased sterol levels and coronary artery disease risk.13 However, these data are not definitive as these variants were also asso-ciated with elevated cholesterol levels. In his rebuttal, Prof Bruckert highlighted the need to consider the weight of evidence as a whole to avoid over-reacting to the results of individual studies. There are also meth-odological issues; in the case of animal stud-ies it is important that the effects of plant sterols are compared against a standardised level of cholesterol intake.

Dr Weingärtner suggested that dietary plant sterol supplementation may be associ-ated with impairment of endothelial func-tion, based on experimental evidence in apolipoprotein E-deficient mice. This study

Is food supplementation with plant sterols useful to prevent cardiovascular disease? Prof Eric Bruckert, Institute of Endocrinol-ogy and Prevention of Cardiovascular Dis-ease, Pitié-Salpêtrière Hospital, Paris, France argued the case for this motion. The effect of individual dietary changes on cardiovas-cular disease (CVD) risk is difficult to evalu-ate in short-term (< 5 years) clinical studies. Therefore evidence to support dietary rec-ommendations is based on a more complex approach.

Extensive data show that consump-tion of plant sterols (1–2 g/day)* has been consistently associated with reduction in plasma concentrations of low-density lipo-protein (LDL) cholesterol by ∼10%. This was recently reaffirmed by a meta-analysis of 84 randomised, controlled studies in 6 805 patients.1 Indeed, recent dyslipidaemia guidelines by the ESC and European Athero-sclerosis Society recommend inclusion of foods supplemented with phytosterols (1–2 g/day) in individuals with elevated total LDL cholesterol for whom total cardiovascular risk assessment does not justify the use of pharmacotherapy.2

* According to the European Food Safety Authority dossier, the efficacy of phytosterol supplementation is proven with a daily dosage in the range of 1.5–2.4 g.


REPORT SA JOURNAL OF DIABETES & VASCULAR DISEASE

also showed increased deposition of sterols in the central nervous system of these mice, suggesting that plant sterols may be able to cross the blood–brain barrier.14 However, he acknowledged that the data are not clear, as other studies have not shown this.15,16 Whether methodological issues, notably differences in the cholesterol content of the diets used in these studies, may explain this is not clear.

In his rebuttal, Prof Bruckert once again argued for a cautious approach when con-sidering data from a single experimental study. In respect of the effect of plant ster-ols on endothelial function, he highlighted evidence from numerous human studies indicating that consumption of plant sterols is instead associated with anti-inflammatory effects, as shown by reduction in levels of C-reactive protein (CRP).17 However, he did agree that there was a need for further study to better understand how and to what extent dietary plant sterols might modify inflammation and the immune system.

In summing up, it was acknowledged that there was a considerable weight of evi-dence for the LDL-lowering effects of die-tary phytosterol supplementation, providing a firm basis for recommendations made by the recent joint ESC/EAS dyslipidaemia guidelines. Beyond LDL cholesterol lower-ing, there is also some evidence to suggest that dietary plant sterols may exert benefi-cial effects on other lipids and biomarkers, such as CRP. Whether these effects translate to prevention of CVD requires further analy-sis. For a definitive answer, long-term, ran-domised, placebo-controlled studies would be the ideal, but are probably unlikely from a practical perspective.

debate was less combative, as both of the participants agreed that diet is an impor-tant part of lifestyle intervention to prevent CVD. The debate therefore hinged on the word ‘alone’.

Prof Horowitz argued the case that diet is a major determinant of the risk for CVD, supported by epidemiologic data. For exam-ple, he cited the Lyon Diet Heart Study,18,19 in which adoption of a Mediterranean diet by myocardial infarction survivors resulted in ∼70% reduction in mortality compared with a comparator group treated with a prudent diet. These data led to termination of the trial. This difference in mortality was evident from three months, was not related to the extent of LDL cholesterol lowering, and the benefit persisted at follow up four years later.

Subsequent studies showed that adher-ence to a Mediterranean diet was inversely associated with CHD risk. Specifically, con-sumption of plant-based foods, and the ratio of mono-unsaturated to saturated fats in the diet were linked with lower choles-terol levels and in turn reduction in the risk of CHD.20 Diet, as part of intensive lifestyle intervention, has also been shown to regress atherosclerosis and improve risk for CVD, in part due to beneficial effects on endothe-lial function and inflammatory markers of atherosclerosis.21

In his conclusions, Prof Horowitz said that these data clearly argue for an early, proactive approach using diet, as part of a comprehensive lifestyle-modification programme, to prevent CVD. Indeed, this approach is already regarded as a funda-mental first step in current guidelines.2

However, as argued by Prof Sleight, long-term adherence is problematic, even among highly motivated individuals. As an exam-ple, he referred to the Nurses’ Health Study in 84 129 women free of diagnosed CVD, cancer and diabetes at baseline. Only 3% of the sample was able to maintain a healthy lifestyle (i.e. not smoking, moderate alcohol consumption, at least 30 minutes of mod-erate physical activity/day, and maintaining a healthy body weight and diet) over the long term.22

Furthermore, he emphasised that in indi-viduals at high risk of CVD, the magnitude of LDL cholesterol reduction achieved with lifestyle is usually insufficient. In such indi-viduals pharmacotherapy is also clearly indi-cated, in line with recent guidelines, with statins the recommended first-line therapy.2

Prof Sleight concluded his presenta-tion by highlighting the need for new

approaches in motivating people to adopt a healthy lifestyle, possibly involving nurse-led intervention programmes, as well as col-laborative approaches across the spectrum of healthcare professionals.

In conclusion, both participants of the debate agreed that diet, as part of inten-sive lifestyle modification, is a fundamen-tal first step in the prevention of CVD. An early, proactive approach is key to reduc-ing lifetime cardiovascular risk. However, it was recognised that motivation and non-adherence are the most important stum-bling blocks in the long term. Additionally, in high-risk patients, diet alone is usually insufficient to achieve sufficient reduction in LDL cholesterol levels as recommended by guidelines.

ReferencesDemonty I, Ras RT, van der Knaap HC, et al. 1. Continuous dose–response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. J Nutr 2009; 139: 271–284.Reiner Z, Catapano A, de Backer G, 2. et al, ESC/EAS guidelines for the management of dyslipidaemias. The Task Force on the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011; doi: 10.1093/eurheartj/ehr158.Law MR, Wald NJ, Rudnicka AR. Quantifying effect 3. of statins on low-density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. Br Med J 2003; 326: 1423.Benn M, Nordestgaard BG, Grande P, Schnohr 4. P, Tybjærg-Hansen A. PCSK9 R46L, low-density lipoprotein cholesterol levels, and risk of ischemic heart disease. J Am Coll Cardiol 2010; 55: 2833–2842.Wilund KR, Yu L, Xu F, 5. et al. No association between plasma levels of plant sterols and atherosclerosis in mice and men. Arterioscler Thromb Vasc Biol 2004; 24: 2326–2332. Fassbender K, Lütjohann D, Dik MG, 6. et al. Moderately elevated plant sterol levels are associated with reduced cardiovascular risk – the LASA study. Atherosclerosis 2008; 196: 283–288.Escurriol V, Cofán M, Moreno-Iribas C, 7. et al. Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort. J Lipid Res 2010; 51: 618–624.Trautwein EA, Demonty I, Ras RT. Plant sterols – a 8. dietary approach for effective blood lipid lowering as part of a heart healthy diet. Curr Topics Nutraceut Res 2010; 8: 137–148.März W. Plant sterols and cardiovascular disease: A 9. systematic review and meta-analysis. Latebreaker abstract, EAS 2011, Gothenburg, Sweden, June 2011. Barter PJ, Caulfield M, Eriksson M, 10. et al; ILLUMINATE investigators. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007; 357: 2109–2122.Forrest MJ, Bloomfield D, Briscoe RJ, 11. et al. Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br J Pharmacol 2008; 154: 1465–1473.

Is diet alone sufficient to reduce cardiovascular risk?This motion was debated by Prof Steven F Horowitz, Stamford Hospital, USA (for) and Prof Peter Sleight, Oxford, UK (against). This


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This report has been funded by an edu-cational grant from Danone.

Weingartner O, Lutjohann D, Ji S, 12. et al. Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol 2008; 51: 1553–1561.Teupser D, Baber R, Ceglarek U, 13. et al. Genetic regulation of serum phytosterol levels and risk of coronary artery disease. Circ Cardiovasc Genet 2010; 3; 331–339.Weingartner O, Ulrich C, Lutjohann D, 14. et al. Differential effects on inhibition of cholesterol absorption by plant stanol and plant sterol esters in apoE2/2 mice. Cardiovasc Res 2011; 90: 484–492.Plat J, de Jong A, Volger OL, Princen HM, Mensink 15. RP. Preferential campesterol incorporation into various tissues in apolipoprotein E*3-Leiden mice consuming plant sterols or stanols. Metabolism 2008; 57: 1241–1247.Jansen PJ, Lutjohann D, Abildayeva K, 16. et al. Dietary plant sterols accumulate in brain. Biochem Biophys Acta 2006; 1761: 445–453.

Othman RA, Moghadasian MH. Beyond 17. cholesterol-lowering effects of plant sterols: clinical and experimental evidence of anti-inflammatory properties. Nutr Rev 2011; 69: 371–382.De Lorgeril M, Renaud S, Mamelle N, 18. et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 1994; 343: 1454–1459.De Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye 19. J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 1999; 99: 779–785.Trichopoulou A, Costacou T, Bamia C, Trichopoulos 20. D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 2003; 348: 2599–2608.Dod HS, Bhardwaj R, Sajja V, 21. et al. Effect of intensive lifestyle changes on endothelial function

and on inflammatory markers of atherosclerosis. Am J Cardiol 2010; 105: 362–367.Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett 22. WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med 2000; 343: 16–22.

Diabetes diary for 2012 congresses

DATE PLACE CONFERENCE

8–11 February Barcelona, Spain 5th International conference on advanced technologies and treatments for diabetes

15–17 February Istanbul, Turkey 1st American Society of Nutrition Middle East Congress ‘Nutrition in Health and Disease’

7–9 March Glasgow, UK Diabetes UK professional conference 2012

19–22 March Harrogate, UK Society for Endocrinology BES 2012

22–25 March Rio de Janeiro, Brazil 2nd Latin America congress on controversies to consensus in diabetes, obesity and hypertension

29–31 March Riga, Latvia AdiT 2012 – 4th International conference on advances in diabetes and insulin therapy

19–22 April Bantry Bay, South Africa SEMDSA/NOFSA 2012 congress

5–9 May Florence, Italy European congress of endocrinology

9–12 May Lyon, France 19th European congress on obesity

24–27 May Bonita Springs, USA 27th Annual clinical conference on diabetes

8–12 June Philadelphia, USA 72nd American Diabetes Association scientific sessions (ADA)

23–26 June Houston, Texas, USA ENDO 2012

22–24 July South Africa Centres for Diabetes and Endocrinology (CDE)

13–16 September Heidelberg, Germany EMBO/EMBL Diabetes and obesity symposia

1–5 October Berlin, Germany 48th European Association for the Study of Diabetes annual Meeting (EASD)

10–13 October Istanbul, Turkey ISPAD 2012 – 38th annual Meeting of the International Society for Pediatric and Adolescent Diabetes

7–9 November Leeds, UK 40th Pacific Paediatric Endocrine Society biennial scientific meeting

22–25 November Athens, Greece Controversies to consensus in diabetes, obesity and hypertension

4–6 December Dubai, UAE 1st American Diabetes Association Middle East Congress ‘Diabetes Prevention and Treatment’


EASD WATCH SA JOURNAL OF DIABETES & VASCULAR DISEASE

TABLE OF CONTENTSDIABETES EPIDEMIC DEMANDS GLOBAL ACTION:

FROM THE UN SUMMIT ON NON-COMMUNICABLE DISEASES ......................................................... 178

Novel treatments ................................................ 178

SGLT-2 inhibitors ................................................. 179

Exenatide vs liraglutide ........................................ 179

46th Minkowski lecture ...................................... 179

ADVANCES IN IMPLEMENTING LIFESTYLE CHANGES Improving health outcomes through peer diabetes

education: lessons for primary healthcare ......... 180

BRAIN CONTROL OF SATIETY AND APPETITEBrain responses to food ...................................... 180

Gastric bypass alters central appetite control ....... 180

Other consequences of bariatric surgery: insulin sensitivity improves only in DM patients ........... 180

High risk of depression in type 2 diabetics: motivation for monitoring of emotional well-being in collaborative care models ............ 181

NUTRITION AND TYPE 2 DIABETES ...................... 181

CLINICAL TRIALS OF INTENSIVE GLUCOSE LOWERING End-stage kidney disease (ESKD): ADVANCE trial ... 181

Understanding cardiovascular risk at HbA1c levels below 7%: ACCORD trial ................................. 181

UKPDS UPDATED RISK MODEL ............................ 181

INCRETIN MIMETICS: THE FUTURE OF TYPE 2 DIABETES MANAGEMENT ................................ 182

Once-a-year GLP-1 dosage passes phase 2 trial ... 182

Liraglutide, the human GLP-1 analogue: safe in mild and moderate renal impairment in type 2 diabetes ........................................................... 182

Achieving weight loss with incretin-based therapies, GLP-1 agonists and DPP-4 inhibitors ................. 182

Maintaining weight loss with liraglutide on adding insulin detemir: one-year follow-on results ....... 182

The promise of DPP-4 inhibitors: use them early in the disease process....................................... 183

CARDIOVASCULAR FOCUS IN DIABETES Provocative suggestion: that DPP-4 inhibitors could

have a cardiovascular protection affect? ........... 183

Type 2 diabetes patients with non-albuminuric renal impairment are still exposed to coronary events 183

Nephropathy ....................................................... 183

Cardiovascular events and risk in type 2 diabetes: the latest insights and clinical trials ........................ 183

MICROVASCULAR COMPLICATIONS: PERIPHERAL NEUROPATHY AND THE DIABETIC FOOT .......... 183

Charcot foot ....................................................... 183

FIELD study: fenofibrate reduction of amputations explored........................................................... 184

DIABETES EPIDEMIC DEMANDS GLOBAL ACTION: FROM THE UN SUMMIT ON NON-COMMUNICABLE DISEASES Diabetes remains on its relentlessly upward trajectory. The International Diabetes Federation (IDF) figures for 2011 are 366 million people with diabetes globally. Deaths due to diabetes will number 4.6 million, with one person dying every seven seconds of complications related to diabe-tes.

The global diabetes community expects commitment from international political leaders at the UN Summit on Non-Com-municable Diseases (NCDs) focusing on the challenge posed by diabetes, cancer, heart and lung diseases. The Summit has the intention of creating concrete actions and measurable targets for prevention and control of NCDs worldwide, with particu-lar focus on developing countries.

Leading experts attending the EASD meeting demanded increased funding for research as a key commitment arising from the Summit. IDF President Jean-Claude Mbanya and EASD vice-president Andrew Boulton (South Africa) have jointly com-mented that ‘without urgent research into improved care and prevention models, we stand little chance of meeting any long-term targets that arise from the Summit’. Research into strengthening health sys-tems should include developing and evaluating approaches for building care capacity, as well as integrating diabetes care with primary healthcare services that offer management of chronic infectious diseases and maternal and child health.

Source: UN/NCD press release

Novel treatmentsIn a session on novel agents in development for the management of type 2 diabetes, interesting new molecules were described. These included a GPR40 protein agonist

2011 UPDATE FROM LISBON, PORTUGALEuropean Association for the Study of Diabetes 12–16 September 2011Contributors: L Lombard, G Hardy, J Aalbers

SUMMARIES

EASD WATCH

(TAK-875) studied in a phase-two trial and compared to 4 mg glimepiride.1

There were 426 patients in the 12-week study, which achieved a 1% lowering in HbA1c levels, equal to that of glimepiride 4 mg. More than 40% of the patients achieved an impressive ≥ 1.5% lowering in HbA1c levels. There were fewer incidents of hypoglycaemia compared with glimepiride and few reported side effects. This mole-cule holds promise for the future.

Another agonist, GPR119 (PSN-821) was also presented in a phase 1 trial. This receptor is present on the beta-cells as well as in the gastrointestinal tract.2 Pre-vious studies have shown increased levels of insulin, GLP1, GIP and PYY. This study showed lowering of LDL cholesterol and of fasting blood glucose of 2 mmol/l.

It was a small study with only 25 patients who experienced no serious side effects. There was a tendency towards weight loss. HbA1c levels were not assessed and there were small changes in both fasting and postprandial glucose levels reported. The results were less impressive than the above study, although it was only in phase 1.

Another product developed and tested in a phase 1 trial was a glucokinase acti-vator in the liver. It showed several side effects and it appears that further develop-ment will not continue.3

Two speakers presented data on gluca-gon receptor antagonists. Although show-ing slight increases in liver enzyme levels, they displayed good lowering in HbA1c levels of 1–1.5%. One of the drugs has a very long half-life.


SA JOURNAL OF DIABETES & VASCULAR DISEASE EASD WATCH

Unfortunately, increased LDL and total cholesterol levels might be a worry for the future. These were also early phase 1 and 2 trials and we await new developments on these products.4,5

Source: 1. Viswanathan, et al. A randomised, double-blind, placebo- and active-controlled, dose-ranging study to determine the efficacy and safety of the novel GPR40 agonist TAK-875 in subjects with type 2 diabe-tes mellitus. Presentation 187.2. Goodman ML, et al. Orally administered GPR119 agonist PSN821 shows clinically significant glucose low-ering and other potential cardiometabolic benefits in patients with type 2 diabetes. Presentation 188.3. Bue-Valleskey JM. LY2599506, a novel glucokinase activator (GKA), improves fasting and postprandial glu-cose in patients with type 2 diabetes mellitus. Presenta-tion 189.4. Prince MJ, Short-term treatment with glucogon receptor antogonist LY 2409021 effectively reduces fasting blood glucose (FBG) and HbA1c in patients with type 2 diabetes mellitus. Presentation 190.5. Engel SS. Efficacy and safety of the glucagon receptor antagonist, MK-0893, in combination with metformin or sitagliptin in patients with type 2. Presentation 190

SGLT-2 inhibitorsA whole session was dedicated to selective glucose transporter-2 (SGLT-2) inhibitors, which are a new class of agents that inhibit glucose re-uptake in the proximal tubule of the nephron of the kidney. Dr Henry pre-sented an eloquent talk on dapagliflozin with or without metformin.1 This was a 24-week randomised, double-blind, active control study with 640 patients in the trial.

The results showed a 2% lowering of HbA1c levels with a 5-mg combination dose of dapagliflozin and metformin. This was more or less equal to the 10-mg dose, where about 3.3 kg weight loss was achieved. The main side effects were increase in incidents of vulvovaginitis, as well as balanitis, a slight increase in haematocrit, and lowering in uric acid level and systolic blood pressure of 3–4 mmHg. There were no hypoglycaemic incidents in the study.

Another study on dapagliflozin com-bined with metformin, presented by Dr Bailey, was a randomised, double-blind, placebo-controlled trial over 102 weeks.2 Compared to the study presented by Henry, the results was positive. The results with 5 mg dapagliflozin combined with metformin were not as impressive (0.58% lowering in HbA1c levels) as 10 mg dapagliflozin plus metformin, which showed a 0.78% lower-ing in HbA1c levels. Body weight reduction was similar to that of the Henry study, with a weight loss of between 2.8 and 3.4 kg.

Another new agent, empagliflozin, was

explored in studies by groups from Amer-ica and Germany, presented by Prof Julio Rosenstock.3 This was a dose-finding study in 495 patients over a period of 12 weeks. This was compared to sitagliptin and showed more or less equivalent HbA1c low-ering of –0.6% and a 1.5-kg weight loss. Fasting blood glucose levels were lowered more than with sitagliptin.

Source: 1. Henry R, et al. Dapagliflozin, metformin-XR or both together to initiate pharmacologic therapy for type 2 diabetes. Presentation 145.2. Bailey CT, et al. Sustained efficacy of dapagliflozin when added to metformin in type 2 diabetes inad-equately controlled by metformin monotherapy. Pres-entation 146.3. Rosenstock J, et al. ENCORE: efficacy and safety of BI 10773, a new sodium glucose co-transporter-2 (SGLT-2) inhibitor, in type 2 diabetes patients inadequately con-trolled on metformin. Presentation 147.

Exenatide vs liraglutideThe DURATION-6 trials evaluating exenatide once a week versus liraglutide head to head in a 1.8-mg dose with a 26-week follow-up period were presented. The liraglutide was up-titrated to a dose of 1.8 mg per day and exenatide was used in a 2-mg per week formulation.

The primary objective was lowering of HbA1c levels after 26 weeks of follow up; 912 patients were randomised. GLP-1 analogues are known to have significant gastrointestinal side effects and withdraw-als on many of these trials have been problematic in the past.

Compared to exenatide once a week, there was slightly more withdrawals due to side effects in the liraglutide group. How-ever liraglutide was more effective than weekly exenatide, which lowered HbA1c levels by 1.28% after 26 weeks, with a 2.68-kg weight loss (both statistically sig-nificant). Liraglutide lowered HbA1c levels 1.48% with a 3.58-kg weight loss. Both of these results were superior to the exenatide once-a-week dosage, although with slightly more side effects.

Both exenatide and liraglutide lowered systolic blood pressure, as was showed in previous trials. The side-effect profile of liraglutide was significantly worse than the once-a-week exenatide, but the effect was slightly superior.

None of these agents is currently avail-able in this form in South Africa. Liraglutide is soon to be launched by Novo Nordisk in our country and it is unknown when exenatide once-a-week dosage will be

available. Both of these treatments will add significantly to our armamentarium and are keenly awaited.

Source: Buse JB, et al. Efficacy and safety of exenatide once weekly versus liraglutide in subjects with type 2 diabetes (DURATIO-6): a randomised, open-label study. Presentation 75.

46th Minkowski lectureProf Naveed Sattar from Glasgow presented a lecture titled ‘Exploiting biomarkers in large datasets for insights into diabetes and cardiovascular disease’. One of his first con-clusions was that ALT levels, as a marker of liver dysfunction, increase with more meta-bolic abnormalities, while AST levels tend to stay fairly stable. In a meta-analysis, ALT was also shown to be a predictor of future diabetes risk.

NAFLD (non-alcoholic fatty liver disease) has been shown to have a 2.5 hazard ratio for the development of diabetes. ALT was also shown to be linked to diabetes, with a 2.02 hazard ratio for the top quartile com-pared to the bottom quartile of ALT as a predictor of developing type 2 diabetes.

The profile of fatty liver disease associ-ated with diabetes is usually with ALT levels raised more than those of AST. Gamma GT is usually also raised, while HDL cholesterol is low, with the patient being overweight and glucose levels being abnormal. It was also shown that accumulation of liver fat could be decreased by regular exercise and increased fibre intake.

Sattar also showed data on the complex-ity of the interaction between adiponectin and insulin resistance and suggested that the association between adiponectin and diabetes is not as simple as previously thought. He also stated that 50 to 70% of patients with type 2 diabetes have a variant of fatty liver disease.

He went on to challenge the statement that type 2 diabetes is a cardiovascular risk equivalent, and showed data to suggest that this is not true at diagnosis. However, the diabetic person’s lifetime risk for cardio-vascular disease is definitely increased and the duration of the disease is an important component of this risk.

He also showed that when fasting glu-cose was used as a predictor of cardiovas-cular risk, cardiovascular disease (CVD) only increased when fasting glucose exceeded 6 mmol/l. Below this level, fasting glucose was not associated with increased CVD. Further data showed that of all the CVD



risk factors, blood pressure lowering is the most efficient way of lowering cardiovascu-lar risk, compared to glucose lowering and treatment for high cholesterol levels.

Another interesting statistic recently published was that statin therapy increased the incidence of diabetes. For every three cardiovascular events prevented by using statins, one new diabetic was produced. Therefore patients with low cardiovascular risk and high risk of developing diabetes should not necessary be treated with stat-ins.

Source: 46th Minkowski lecture, EASD, Prof N Sattar.

ADVANCES IN IMPLEMENTING LIFE-STYLE CHANGES

Improving health outcomes through peer diabetes education: lessons for primary healthcareDiabetes requires a life-long process of self-care, treatment and lifestyle changes. It is commonly accepted that diabetes patients should be made aware of the signs, symp-toms and consequences of the disease. Studies relating to peer education for improving health outcomes in diabetes are rare in developing countries.

An exception was the presentation of the recent Bangladesh study on the effec-tiveness of diabetes education with pro-fessional versus peer leaders. Among the peer leader group, significant reductions in systolic blood pressure, fasting blood glucose and HbA1c levels were found. Edu-cational intervention by professionals also resulted in significant reductions in HbA1c levels.

Fasting blood glucose was more sig-nificantly reduced in the peer leader group compared to the professional group. Study subjects of the professional group had significantly better diastolic blood pres-sure compared to the peer leader group. This emphasises the value of South Africa’s approach of using lay community workers to support the healthcare team.

Source: Khan F, et al. Effectiveness of diabetes educa-tion on improving glycaemic achievement by profes-sionals versus peers. Presentation 66.

Improved peer education outcomes for diabetic footThe significance of diabetic education on prevention and prognosis of diabetic foot

ulcers (DFU) was examined in China, where 33% of DFUs result in amputation. Find-ings indicated that individualised diabetic education may decrease the incidence of DFU, retard the progress of diabetic foot and reduce amputation rate and mortality.

Source: Zhenghua X, et al. Individualised diabetic edu-cation can contribute to decrease the incidence of dia-betic foot and avoid amputation: results of a 9-year prospective study. Presentation 61.

BRAIN CONTROL OF SATIETY AND APPETITE

Satiety signalling in type 2 diabetesAltered central satiety signalling in type 2 diabetes may be a barrier to weight loss. A surrogate marker of neuronal activation (changes in regional cerebral blood flow) has been used to examine the effect of type 2 diabetes on neuronal responses to feeding.

Findings indicated that altered central satiety signalling in T2DM may be a barrier to weight reduction and lifestyle manage-ment in the treatment of T2DM.

Source: Lee S, et al. Impact of type 2 diabetes on hunger and brain responses to eating: a continuous arterial spin labelling functional magnetic resonance imaging study. Presentation 135.

Brain responses to foodEating behaviour is also controlled by cor-ticolimbic responses to food cues, which mature in man from childhood to early adulthood. Changes in such higher-func-tioning brain responses observed in obesity and type 2 diabetes may be implicated in their aetiology. Central control of appetite is an attractive target for weight reduction and diabetes control.

Considering the increased risk of obesity and type 2 diabetes as an individual ages, Cheah and colleagues have investigated the effect of advancing age in adults on cor-ticolimbic responses. It is established that BMI influences regional brain responses to food cues. Age may independently influ-ence neural network responses to food that control appetite and eating behaviour. Reduced activation of these pathways may result in reduced control of food intake, which may be involved in the increased risk of obesity with rising age.

Source: Cheah YS, et al. Both ageing and body mass modulate the human brain response to food cues. Pres-

entation 133.

Gastric bypass alters central appe-tite controlThe role of the proximal intestine in the pathophysiology of type 2 diabetes mellitus has been the subject of growing interest. Gastric bypass surgery has been shown to resolve type 2 diabetes but the underlying mechanisms are incompletely understood. Studies have examined the improvement in glucose metabolism after gastric bypass surgery.

Hunt and colleagues proposed that changes in gut-to-brain communication following Roux-en-Y gastric bypass (RYGB) may modulate central control of appetite. Findings indicate that the pattern of central neuronal deactivation in response to food ingestion is similar in those who have had RYGB and individuals of normal weight, but different from obese individuals who have not had surgery. These patterns may explain increased satiation with eating and the weight loss seen post-RYGB.

Source: Hunt KF, et al. The brain’s response to food ingestion after Roux-en-Y gastric bypass: a [18F]-fluoro-deoxyglucose positron emission tomography (FDG-PET) study. Presentation 137.

Other consequences of bariatric surgery: insulin sensitivity improves only in DM patientsSvehlikova and colleagues quantified changes in insulin sensitivity1 before and shortly after gastric bypass surgery in type 2 diabetic (DM) patients and non-diabetic patients (non-DM) with severe obes-ity. Improvement in insulin sensitivity was marked in DM patients, independent of duration of disease. No such post-opera-tive changes were observed in the non-DM group.

Despite a markedly enhanced GLP-1 response in an oral glucose tolerance test, there was only a mild improvement in insu-lin secretion, which still remained impaired when compared to non-DM patients. An unexpected enhanced rise in glucagon levels during OGTT points to a substan-tial stimulatory effect of gastric bypass on alpha-cell function.

The hypothesis that intestinal insulin resistance is an important factor in the pathophysiology of type 2 diabetes was investigated by Makinen and colleagues.2 Their aim was to non-invasively quantitate intestinal insulin-stimulated glucose uptake (GU) in obese patients before and after bariatric surgery.



This study demonstrates that obese sub-jects with and without type 2 diabetes have significant insulin resistance in the proximal intestine. Jejunal GU is improved in line with whole-body and skeletal muscle insu-lin sensitivity after bariatric surgery and the recovery of diabetes. The findings suggest that intestinal insulin resistance is an impor-tant factor in T2DM.

Source: 1. Svehlikova E, et al. Improved glucose metab-olism early after gastric bypass surgery relies primarily on enhanced insulin sensitivity. Presentation 182. 2. Makinen J, et al. Intestinal insulin resistance asso-ciated with obesity and type 2 diabetes. Presentation

185.

High risk of depression in type 2 diabetics: motivation for monitor-ing of emotional well-being in col-laborative care modelsThe risk of depression is doubled in individ-uals with type 2 diabetes, often presenting as a chronic condition.

The incidence and recurrence/persist-ence of depression and significant pre-dictors thereof have been examined in a cohort of 2 460 primary-care patients with type 2 diabetes. Female gender, low levels of education, microvascular disease, other co-morbid conditions and stressful life events were all positively associated with incident depression. Low educational level was the only significant predictor of recur-rent/persistent depression.1

Diabetes has a considerable impact on health-related quality of life (HRQL). A prog-nostic link between self-reported HRQL and unfavourable outcome has not been well explored in patients with type 2 diabetes and acute myocardial infarction.

It was found that a low self-reported HRQL score is of prognostic significance and can therefore serve as an easily obtained indicator of patients at high risk for all-cause and cardiovascular mortality. The predictive value appeared to be higher in men.2

Source: 1. Kjellstrom B, et al. Health-related quality of life predicts survival in patients with type 2 diabetes and myocardial infarction: a report from the DIGAMI2 trial. Presentation 6. 2. Nefs G, et al. The course of depression in primary care patients with type 2 diabetes: results from the DiaDDZoB study. Presentation 213.

NUTRITION AND TYPE 2 DIABETES There is still limited understanding on how dietary macronutrient composition is linked

with long-term risk of obesity-related chronic disease.

Diets high in protein have shown prom-ising results on short-term weight reduction and glycaemic control. However, high-pro-tein diets were associated with increased risk of type 2 diabetes. Replacing protein with carbohydrates, particularly fibre-rich breads and cereals, was inversely associ-ated with type 2 diabetes.1

The increased consumption of a West-ern diet high in refined sugar and fat has led to increased rates of obesity, insulin resistance and type 2 diabetes mellitus. The effect of high sugar intake in adolescence is less well demonstrated.

Lewis and colleagues have studied the effect of sugar intake in early teenage years on glucose tolerance and insulin resistance in early adulthood. Higher dietary sugar intake in early teenage years independently affected longer-term glucose metabolism and was associated with higher fasting plasma glucose and relative insulin resist-ance. There was no such association for high dietary sugar intake in early adult-hood. These findings indicate a potential legacy effect of the adolescent diet and a need to address dietary advice in this age group

The ability to identify obese subjects who will lose weight in response to energy restriction is an important strategy in clini-cal care of obesity. Kong and colleagues have concluded that individual responses to hypocaloric high-protein, fibre-rich dietary programmes could be predicted by plasma insulin, IL-6, leukocyte numbers and adi-pose tissue HAM56 levels prior to diet.3

Source: 1. Ericson UC, et al. High intake of protein and processed meat is associated with increased incidence of type 2 diabetes. Presentation 13.2. Lewis AS, et al. A prospective longitudinal observa-tional study on the effect of dietary sugar intake in ado-lescence and early adulthood on measures of glucose metabolism in early adulthood. Presentation 237. 3. Kong L, et al. Plasma insulin and inflammatory mark-ers prior to weight loss can predict dietary responders. Presentation 16.

CLINICAL TRIALS OF INTENSIVE GLUCOSE LOWERING

End-stage kidney disease (ESKD): ADVANCE trialBlood glucose levels have been linked to the risk of kidney disease, but the effects of intensive glucose control on major kidney outcomes among people with diabetes are not known. An analysis from the ADVANCE

trial found that an intensive blood glucose-lowering regimen (HbA1c < 6.5%) based on gliclazide MR reduced the risk of ESKD, but the effects on other renal outcomes were less clear.

Source: Zoungas S, et al. Intensive glucose lowering and end-stage kidney disease: new data from the ADVANCE trial. Presentation 39.

Understanding cardiovascular risk at HbA1c levels below 7%: ACCORD trialThe ACCORD trial reported significantly higher mortality in type 2 diabetes patients treated with intensive glucose lowering (target HbA1c < 6%) versus standard treat-ment (target HbA1c 7–7.9%). The ACCORD findings are contextualised with outcomes estimated from other data sources, by com-parison of relative risks of non-fatal MI, non-fatal stroke, heart failure and all-cause mortality.

Relative risk of all-cause mortality in ACCORD was significantly different from pre-vious data. This difference was not seen in the other endpoints, was not consistent across recent studies and was not fully explained by hypothesising a lower limit of 7% for HbA1c benefit. Observed mortality effects in the ACCORD trial may have been related to fac-tors other than glucose lowering.

Source: Foos V, et al. Comparison of ACCORD trial out-comes with outcomes estimated from modelled and meta-analysis studies. Presentation 3.

UKPDS UPDATED RISK MODEL The United Kingdom Prospective Diabetes Study (UKPDS) outcomes simulation model for type 2 diabetes predicts development and consequences of diabetes complica-tions, enabling economic evaluation of inter-ventions. This model has been extended and enhanced, with additional risk factors.

Micro- or macroalbuminuria was a signif-icant covariate in eight equations (including death and renal failure); peripheral vascular disease was significant in seven equations (including death and amputation) and white blood cell count in four equations (including first stroke and blindness). Nota-bly, atrial fibrillation was associated with high risk of first stroke and heart failure.

Source: Hayes AJ, et al. An improved model to estimate lifetime health outcomes of patients with type 2 diabe-tes using 30-year follow-up data from the United King-dom prospective diabetes study. Presentation 4.



Key notes on macrovascular complications

• Advanced glycation end products (AGE) are not found in higher concentrations in the atherosclerotic plaque of diabetics, compared to patients without diabetes undergoing carotid endarterectomy (Presentation 1264).

• An HbA1c level of 6.3% has the lowest risk of cardiovascular events and mortality, according to a study of 40 000 type 2 diabetes patients in a Swedish registry (Presentation 153).

• The use of a serum glycated albumin (GA)/HbA1c ratio was found to be useful in type 2 diabetes Japanese patients, with values above 3% being indicative of presence of plaque (Presentation 1265).

• The newly developed Canadian iScore, used after ischaemic stroke, has been shown to have a high predictive accuracy also in diabetes patients (Presentation 1254).

• In non-diabetics who are at high risk of developing diabetes, a yearly increase in the normal HbA1c level (5.7%) of 0.1% was associated with an increase in aortic stiffness comparable to being two years older (Presentation 152).

• Obesity without insulin resistance does not raise and seemed to lower cardiovascular disease risk, according to a six-year follow-up study comparing ‘metabolically benign obesity’ to normal-weight individuals with insulin resistance (Presentation 222).

• Non-alcoholic fatty-liver disease (NAFLD), as measured by liver ultrasound scan and biochemically, is a major risk factor for cardiovascular events in patients with type 2 diabetes. These patients should be treated and cared for by both an internist and a cardiologist, as their cardiovascular events are three times that of type 2 diabetes patients without NAFLD (Presentation 246).

INCRETIN MIMETICS: THE FUTURE OF TYPE 2 DIABETES MANAGE-MENTA miniature osmotic pump the size of a matchstick may revolutionise treatment of type 2 diabetes with insulin mimetics (and perhaps other agents).

Once-a-year GLP-1 dosage passes phase 2 trialThe DUROS subcutaneous delivery system is currently being used with exenatide in phase 2 trials. This system offers patients and their healthcare systems a once-a-year non-injectable exenatide, which delivers continuous and consistent levels of this GLP-1 agonist.

The investigational study of ITCA 650, as it is called, has now determined a likely dose regimen for phase 3 trials on an ini-tial three-month ITCA 650 dosing of 20 µg/day, followed by the subcutaneous implan-tation of a second device for 6- and 12-µg duration supplying 60 µg/day.

The phase 2 trial results showed con-sistent plasma levels of exenatide up to 48 weeks with undetectable levels within 24 hours of device removal. Patients in the trial showed sustained reductions in HbA1c levels, FPG and weight reduction. Side effects were greatly reduced and there were no discontinuations due to nausea.

The DUROS device is also in phase 2 clinical studies in prostate cancer research, delivering androgen reduction therapy.

Source: Luskey K, et al. Presentation 77. EASD Oral Presentation

Liraglutide, the human GLP-1 analogue: safe in mild and moderate renal impairment in type 2 diabetesA meta-analysis of seven clinical trials has assessed the safety and efficacy of once-daily liraglutide in mild (estimated creatine clearance < 90 ml/min) renal impairment.

This review showed that reductions in HbA1c levels were similar regardless of renal impairment. The proportion of any patients experiencing major hypoglycaemic episodes was very low (0–0.2%) and not related to renal function. Minor hypogly-caemic events seemed lower in the renal-impaired group and overall, liraglutide was effective and well tolerated in these type 2 diabetes patients.

Source: Gough S, et al. Reductions in HbA1c and the incidence of hypoglycaemic episodes are not affected by renal impairment in patients with type 2 diabetes, treated with liraglutide. Presentation 822.

Achieving weight loss with incre-tin-based therapies, GLP-1 agonists and DPP-4 inhibitorsThis study of the data of approximately 1 200 patients treated in two large, ran-domised trials was used to determine the number of patients reaching the target HbA1c level of less than 7% and weight loss after 26 weeks of treatment with either liraglutide 1.8 mg or 1.2 mg daily on top of metformin and/or sulphonylurea therapy.

Patients receiving the higher dose of liraglutide were most likely to reach target HbA1c levels and achieve weight loss (–3 kg) than on the other two therapies. This was a post-hoc evaluation, which supports avail-able clinical trial data on these agents.

Source: Zinman, et al. Achieving glycaemic control and weight loss with incretin-based therapies. Presentation

798.

Maintaining weight loss with liraglutide on adding insulin detemir: one-year follow-on resultsThe issue of weight loss in the face of adding insulin to a type 2 diabetes patient’s regimen is one that troubles patients and their clinicians.

Further follow up of patients on met-formin and liraglutide (1.8 mg) for 12 weeks (run-in period) who were not achieving their HbA1c target levels and then randomised to continue on oral therapy (keeping HbA1c < 8%) or to receive 10 U insulin detemir daily has shown no weight increase with the addition of insulin detemir in the following 52 weeks. Weight loss continued in those receiving oral therapy only.

Minor hypoglycaemic rates were very low in both arms and no major hypogly-caemic episodes occurred in the one-year treatment period.

Source: Bain SC, et al. Adding insulin detemir (I Det) to liraglutide and metformin improves glycaemic control with sustained weight reduction and low hypoglycae-mic rates: 52 weeks. Presentation 73



The promise of DPP-4 inhibitors: use them early in the disease processAn 18-month study of patients presenting with type 2 diabetes who were not yet on treatment has shown that initial therapy with saxagliptin plus metformin (dual oral therapy) achieved more sustained glycae-mic control than monotherapy using either of these agents.

This randomised, phase 3, double-blind parallel group study1 included 1 300 patients with type 2 diabetes inadequately control-led with diet and exercise. Patients were randomised to oral saxagliptin 5 mg or met-formin; 10 mg saxagliptin plus metformin; 10 mg saxagliptin; or metformin only.

The mean duration of type 2 diabetes was 1.7 years and patients were young (mean age 52 years). The initial dual therapy with saxagliptin (5 or 10 mg) and metformin consistently resulted in more patients achieving glucose control over 18 months than those on metformin only, regardless of the baseline characteristics of the patient.

The results of this approach suggest that glucose control may be more likely when dual oral therapy is initiated early.

A second study (PROMPT) used saxaglip-tin (5 mg/daily) instead of up-titrating met-formin from 1.5 g/day to 2.5 g/day. The saxagliptin addition was better tolerated and achieved similar HbA1c reductions to the larger metformin dose.2

Source: 1. Frederick F, et al. Clinical characteristics and sustained glycaemic control: a 76-week, randomised double-blind study of saxagliptin and metformin in treatment-naïve patients with type 2 diabetes. Presen-tation 8292. Hermans MP, et al. Effects of saxagliptin added to sub-maximal doses of metformin compared with dose calculation of metfomin in type 2 diabetes: results from the PROMPT study. Presentation 828.

CARDIOVASCULAR FOCUS IN DIABETES

Provocative suggestion: that DPP-4 inhibitors could have a cardiovascu-lar protection affectAn evaluation of all available trials with DPP-4 inhibitors used for longer than 24 weeks in type 2 diabetes patients was done to assess issues of cardiovascular safety. Major cardio-vascular events (MACE) were fewer in the patients given DPP-4 inhibitors compared to placebo or another treatments.

While suggesting little more than no adverse events, this arena will require much more attention in randomised controlled

trials for diabetes drugs, as suggested by many cardiovascular experts.

Source: Lamanna C, et al. DPP-4 inhibitors and CV events: a protective effect? Presentation 244.

Type 2 diabetes patients with non-albuminuric renal impairment are still exposed to coronary eventsThis study of 9 865 type 2 diabetes patients from the Renal Insufficiency and Cardio-vascular Events (RACE) trial showed that non-albuminuric renal impairment was more strongly associated with myocardial infarction and the need for coronary revas-cularisation than with stroke or the need for carotid revascularisation. However, patients with micro- or macroalbuminuria had higher rates of coronary events.

Source: Pugliese G, et al. Association of Normoalbu-minuric renal impairment with cardiovascular disease. Presentation 38.

NephropathyIn an interesting talk from the Netherlands, Dr I Drion presented data from a study on diabetic individuals over 75 years of age (Zodiac-24 study) with decreased kidney function. Estimated glomerular filtration rate (GFR) was calculated by the MDRD and Cockcroft-Gault formula.

It is well known that albuminuria and decreased GFR in type 2 diabetes patients is associated with increased cardiovascu-lar mortality. This has not been studied in this age group. Estimated GFR is often decreased in this older population group.

During this study on 347 patients over 75 years, a large percentage died. The patients were stratified into three categories, those with estimated GFR < 45 ml/min/1.73 m2, those with GFR 45–60 ml/min/1.73 m2 and those with > 60 ml/min/1.73 m2.

The study showed that patients with albuminuria had increased risk of mortal-ity, but not those with only GFR 45–60 ml/min/1.73 m2 in the age group over 75 years.

Source: Drion I, et al. Chronic kidney disease and mortal-ity risk among elderly diabetic individuals (ZODIAC-24). Presentation 37

Cardiovascular events and risk in type 2 diabetes: the latest insights and clinical trialsOsteoprotegerin (P-OPG) a bone-related glycopeptide produced by vascular smooth

muscle has been shown to be a useful independent predictor of the presence of coronary artery disease in asymptomatic type 2 diabetes patients with microalbu-minuria.

This Danish study used myocardial per-fusion imaging and CT angiography to cor-relate the presence of arterial disease with P-OPG levels in 200 asymptomatic type 2 diabetes patients. Importantly, patients with low levels of P-OPG did not have sig-nificant artery stenosis.

Source: Reinard H, et al. Osteoprotegerin and CAD in type 2 diabetic patients with microalbuminuria. Presen-tation 1283.

MICROVASCULAR COMPLICATIONS: PERIPHERAL NEUROPATHY AND THE DIABETIC FOOT Peripheral neuropathy, a significant micro-vascular complication of diabetes, leads to impaired quality of life, and is a primary determinant of lower-limb ulcer formation and amputation.

In the UK, it has been found that dia-betic patients of South Asian origin have one-third the risk of foot ulceration com-pared to Europeans. In an attempt to define differences in predisposing risk factors for ulceration, Fadayi and colleagues found that despite worse glycaemic control, Asian patients had better small-fibre func-tion and structure compared to European diabetic subjects. Furthermore, they had higher foot skin oxygenation and hyperae-mic blood flow response to heating, which may protect from the development of foot ulceration.

Source: Fadavi H, et al. Potential explanation for lower incidence of foot ulceration in Asian compared to Euro-pean patients with type 2 diabetes. Presentation 7.

Charcot footThe mechanisms of pathological bone resorption in acute Charcot osteo-arthrop-athy are not fully understood. It has been demonstrated that receptor activator of nuclear factor κβ ligand (RANKL) plays an important role as an activator of osteoclastic resorption in acute Charcot osteo-arthrop-athy. However, it is not known whether RANKL-mediated osteoclastic resorption can be modulated by the pro-inflammatory cytokines TNF-α and IL-6.

Peripheral blood mononuclear cells, which act as osteoclast precursors, were cultured in vitro on bovine disks in the pres-



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ence of (1) macrophage colony-stimulating factor (M-CSF) and RANKL, (2) M-CSF, RANKL and neutralising antibody to TNF-α, and (3) M-CSF, RANKL and neutralising antibody to IL-6.

The addition of neutralising antibody to TNF-α to the cultures with M-CSF and RANKL led to a marked decrease in the osteoclastic resorption only in patients with Charcot osteoarthropathy. The addition of neutralising antibody to IL-6 had a variable effect on the osteoclastic resorption in the three groups. It led to a significant decrease in osteoclastic resorption in patients with acute Charcot osteoarthropathy and to a non-significant decrease in healthy con-trols. Unexpectedly, it led to a significant increase in bone resorption in patients with diabetes.

The potential role of agents reducing pro-inflammatory cytokines remains uncer-tain in treatment of Charcot foot.

Source: Petrova NL, et al. The proinflammatory cytokines TNF-α and IL-6 modulate RANKL-mediated osteoclas-tic resorption in vitro in patients with acute Charcot osteoarthropathy. Presentation 11.

FIELD study: fenofibrate reduction of amputations exploredIn this large study of type 2 diabetes patients on treatment with co-micronised fenofibrate 200 mg per day, foot sensation as measured by monofilament test improved. This is likely to be the basis of the 37% reduction in amputations found in the added fenofibrate arm of the FIELD study.

The presence of peripheral neuropathy was assessed by standard 10-G monofila-ment at baseline, year two, and at study close after five years; 17.2% of participants had features of peripheral neuropathy at baseline (1 125 with symptoms only, 564 had abnormal monofilament assess-ment).

Prevalence of abnormal monofilament test at the end of the study was signifi-cantly lower in the fenofibrate arm (6.9 vs 8.2%). The NNT to avoid a first on-study amputation over the five-year study was only 16.

Source: Keech AC, et al. Predictors of peripheral neu-ropathy and effects of fenofibrate among 9,795 sub-jects with type 2 diabetes: the fenofibrate intervention and event lowering in diabetes (FIELD) study. Presenta-tion 180.

Cardiovascular diary for 2012 congresses

DATE PLACE CONFERENCE

1–3 February New Orleans, USA Internatioanl Stroke Conferencewww.heart.org

18 February Frankfurt, Germany TrenD 2012 – Transcatheter renal denervationwww.ici-congress.org

18–21 April Dubai, United Arab Emirates World Congress of Cardiologywww.world-heart-federation.org

3–5 March Southern Sun Cape Sun, Cape Town, South Africa

17th Biennial Congress of the SA Hypertension Society Congress (SAHS)www.hypertension.org.za

17–20 May Berlin, Germany Congress on cardiac problems in pregnancy (CPP 2012)www.cppcongress.com

27 June Frankfurt, Germany ICI 2012 – Imaging in cardiovascular interventionswww.ici-congress.org

28 June Frankfurt, Germany CSI 2012 – Catheter interventions in congenital and structural heart disease

19–22 July Sun City, South Africa 13th Annual SA Heart Congresswww.saheart.org

25–29 August Munich, Germany 2012 ESC – European Society of Cardiology Congresswww.escardio.org

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DIABETES NEWS SA JOURNAL OF DIABETES & VASCULAR DISEASE

Diabetes NewsNew stem cell cryopreservation laboratory in Cape Town

The use of stem cell technology in the therapeutic arena is an increasingly tan-

gible objective in medical science. Currently, the are 70 medical conditions (primarily blood diseases) that can be treated by the application of stem cell technology, with more than 3 000 clinical trials in progress. Future medical applications are continuously being researched and discovered, among which are some showing promising results in human diabetes therapy.

As genetic understanding of type 1 diabe-tes increases, the value of stem cell storage could become a reality. The incidence of type 1 diabetes is on the increase globally. Recent research among children with a family his-tory of type 1 diabetes shows that Western lifestyles and associated overweight/obesity may trigger increased risk of Islet autoim-munity, with associated increased insulin resistance.1

Internationally, trends reflect the impor-tance of stem cell banking. These stem cells can mean the difference between life and death in the case of future threats to the health of the donor. Saving stem cells at birth is truly a once-in-a-lifetime opportu-nity for baby, siblings and parents. There is a one-in-four chance of the tissue matching the siblings and a one-in-eight chance of the tissue matching the parents.

In the USA, transplants performed on patients younger than 18 years of age show that more than 50% of stem cell transplan-tations have cord blood as the cell source. It is legislated in 27 American states that expectant parents have to be informed of the possiblity of stem cell storage by their attending medical expert.

Cryo-Save NV, the leading international family stem cell bank, represented in 40 countries on four continents, already stores 185 000 samples from cord blood and umbilical cord tissue for newborns, and adipose tissue for adults. Cryo-Save South Africa has opened a state-of-the-art stem cell processing and storage laboratory in Cape Town, providing best-practice medical services with sound governance and com-mercial practice.

Cryo-Save South Africa has employed professional, dedicated and highly-skilled staff to operate the new laboratory. Key personnel have undergone specialised train-

ing at Cryo-Save’s state-of-the-art facility in Belgium.

The Cape Town laboratory will immedi-ately process and store cord tissue as well as stem cells from cord blood. To ensure that extracted stem cells are viable, flow cytom-etry testing is performed prior to storage. Cryopreservation storage facilities are not dependant on electricity supply and are iso-lated from external power cuts. Clients have

the option to store in South Africa or Bel-gium, or to select dual storage of a sample in South Africa and in Europe.

G Hardy

Couper JJ, Beresford S, Hirte C, Baghurts PA, Pollard 1. A, Tait BD, et al. Weight gain in early life predicts risk of Islet autoimmunity in children with a first-degree relative with type 1 diabetes. Diabetes Care 2009; 32(1): 94–99.

Case studyA patient with a family history of type 1 diabetes mellitus is delighted that her daugh-ter is pregnant. With the knowledge that the grandchild may be at risk of inheriting this condition, the practitioner feels it suitable to advise stem cell storage from the grandchild. Future stem cell therapy may be beneficial to the lifelong health of the grandchild.

On registration, a collection kit and information pack are sent to the client.• Umbilical cord stem cells are collected immediately after birth by the attending • medical professional with no risk to either mother or child. The procedure is painless and non-invasive and does not affect the natural sequences of birth at all. Specialist medical couriers deliver the sample to the Cape Town laboratory within • 24 hours, where the cells are professionally processed and stored according to the highest international standards.

ContactTel: 0860 STEM CELLS (0860 7836 2355)Tel: +27 11 803 4409Fax: 086 219 9157e-mail: [email protected]: www.cryo-save.co.za


SA JOURNAL OF DIABETES & VASCULAR DISEASE DIABETES NEWS

The Journal was recently invited to attend a diabetes youth camp in Jonkershoek,

arranged by Sister Kamaretha Beckert and Dr Nickie Bernard. A multi-disciplinary team also volunteered their services at the camp. Some 40 children between the ages of 6 and 16 years had the opportunity of attending and learning how to cope and thrive despite their diabetes.

These youth shared experiences and fears in a safe environment. Among the emotions experienced by the child with diabetes are anxiety, anger and depression, as well as fear of needles, death, hospitalisation, rejec-tion and humiliation, and these require care-ful handling.

Ms Rosemary Flynn, clinical psychologist who is also diabetic, had advice for parents. ‘Find a place for the diabetes where it nei-ther rules, nor is neglected. Because of their diabetes, these children may develop spe-cial aptitudes. But they are still children of their particular age, confronting other issues independent of and possibly exacerbated by their diabetic status.’

Getting together: a diabetes youth camp in StellenboschFlynn recommends developing a child-

centred approach within the context of authoritative parenting. ‘Be warm, accept-ing and loving, but clear about the bounda-ries. As parents, you need to cultivate in the diabetic child self control, initiative and an outgoing approach to life.

‘By listening carefully, accepting the child’s view and not getting hooked on the parental agenda, being patient and express-ing your delight in your child’s achievement, big or small, fears and anxieties can be dealt with and placed in a non-dominant sphere’, she concluded.

Innovative support for diabetic lifestylesDo you know about the following useful resources for your young diabetic patients and their parents?• The Blackberry application: Calorie coun-

ter by Fat Secret can really help with carb counting for insulin calculation. The application supplies calorie totals and macro-ingredients of meals from popu-

lar restaurants (Wimpy, St Elmo’s pizzas, Steers and many others) as well as the calorie levels of common foods bought in stores throughout the country.

• The Emotion of Children with Diabetes: this useful and practical guide for parents is by Rosemary Flynn. A CDE-sponsored publication, this book provides a practical guide to coping with the emotional ups and downs of children with diabetes.

• Diabetes vir Kinders: for Afrikaans families, Sr Kamaretha Beckert has created an infor-mation file targeted at those children who have recently been diagnosed with diabe-tes. Available at all Medi-clinics who have partnered in this educational project, this colourful file helps children to understand and manage their condition, with simple clear explanations about the biology and day-to-day requirements of their disease.

• Accu-Chef Cookbook: published by Accu-Check, this is a beautifully illustrated and clearly set out book. The teenager or young adult is likely to find inspiration from this collection of easy-to-make recipes.

Parents and their children getting much-needed support and advice.

Exercise and outdoor activities are essential for staying healthy with diabetes.Dr Landi Lombard chatting to the teenagers about hypoglycaemia.

Young people who attended the diabetes youth camp with their mentors.


DIABETES NEWS SA JOURNAL OF DIABETES & VASCULAR DISEASE

Celebrating World Diabetes Day‘Act on Diabetes Now’2011 marks the third year of the five-year focus on ‘diabetes education and preven-tion’, the theme selected for World Diabetes Day from 2009 to 2013. The campaign calls on all those responsible for diabetes care to ‘act on diabetes now”

With the first-ever UN high-level meet-ing on non-communicable diseases held in September, World Diabetes Day will pro-vide the platform to cement the decisions and outcomes of global decision makers. At the same time, World Diabetes Day will provide impetus and inspiration for the diabetes community when they gather for the World Diabetes Congress in Dubai in December.

With 2011 being a milestone year for the over 300 million people living with diabetes, five key messages have been developed to inform the outputs and deliverables of this 2011 campaign:• Diabetes kills: one person every eight sec-

onds, four million people a year.• Diabetes doesn’t discriminate: all ages,

rich and poor, all countries are affected.• Diabetes can no longer be ignored: four

million lives are lost a year, one million amputations a year, millions are lost in income and productivity.

• Life-saving care, a right not a privilege: education, medicines and technologies are needed, particularly in the developing world.

• Choose health: the general public needs to demand healthy food and environ-ments, and to keep active and eat well.

You can make a difference.

While the campaigns last the whole year, 14 November is the official day, celebrating Frederick Banting’s birthday. He, along with Charles Best first conceived the idea which led to the discovery of insulin in 1922.

What is the world doing for World Diabetes Day in 2011?Here are just a few of the main events com-memorating World Diabetes Day.

The Big Blue Test – you can join in!The Big Blue Test is a diabetes awareness programme celebrated in countries such as the USA, UK and Spain. The Big Blue Test was started by the non-profit Diabetes Hands Foundation, and takes place every

November, leading up to World Diabetes Day, on 14 November this year.

The campaign reinforces the importance of exercise in managing diabetes. People with diabetes are encouraged to do the Big Blue Test on any day between 1 and 14 November at midnight Pacific Time, by test-ing their blood sugar, getting active, testing again, and sharing the results online at big-bluetest.org. Remember: just 14 minutes of exercise decreases participants’ blood sugar levels between 15 and 20%.

In 2010, more than 2 000 people did the Big Blue Test. Over 120 000 people watched the Big Blue Test video. Roche Diabetes Care, makers of Accu-Chek® diabetes products and services, funded the production of the video and incentived participation by donating 75 cents for each of the first 100 000 views, resulting in a total donation of $75 000. The donation provided insulin and supplies to more than 2 000 people with diabetes in developing countries.

In 2011, in proportion to the number of people that do the Big Blue Test, another donation from Roche Diabetes Care will benefit more than 8 000 needy people with diabetes. Five non-profit organisations, focused on helping underserved areas with a high incidence of diabetes in the USA, will each receive $10 000, while $25 000 will go to support the work of the International

Diabetes Federation’s (IDF’s) Life for a Child Programme in Latin America.

World Diabetes Day Blue Monument ChallengeIn 2010 the IDF encouraged a Monument Challenge on 14 November. More than 1 000 iconic sites and buildings around the world were lit up in blue, honouring World Diabetes Day. They encouraged a further challenge for 2011 with already 900 monu-ments scheduled to go blue.

Buildings joining this challenge include: the AAMI Park in Melbourne, the Eye in London, Yula River bridge in China, Cali-fornia State Capital building, USA, and Burj-al-Arab in Dubai. South Africa’s very own Voortrekker Monument in Pretoria has joined the cause by also going blue. Visit Flicker under World Diabetes Day Blue Monument Challenge to view the magnifi-cent sites.

What did South African Diabetes leaders do?Novo Nordisk arranged a Changing Diabe-tes concert, which was held on 5 November. This concert featured South African artists such as Tshepo Mosese, Danny K, Teargas and Kabelo. Their Changing Diabetes bus was also on site for free diabetes screening, creating awareness of the disease.

A really effective diabetes screening initiative, Novo Nordisk’s bus is popular whereever it goes, often into rural areas in South Africa.

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References1. Blonde L et al. Patient-directed titration for achieving glycaemic goals using a once-daily basal insulin analogue: an assessment of two different fasting plasma glucose targets – the TITRATE™ study. Diabet. Obes. and Metab. 2009;11:623–631. 2. Philis-Tsimikas A et al. Comparison of Once-Daily Insulin Detemir with NPH Insulin Added to a Regimen of Oral Antidiabetic Drugs in Poorly Controlled Type 2 Diabetes. Clin Ther 2006;28(10):1569–1581. 3. Rosenstock J et al. A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetologia 2008;51:408–416. 4. Hermansen K et al. A 26-Week, Randomized, Parallel, Treat-to-Target Trial Comparing Insulin Detemir With NPH Insulin as Add-On Therapy to Oral Glucose-Lowering Drugs in Insulin-Naïve People with Type 2 Diabetes. Diabetes Care 2006;29(6):1269–1274. 5. Klein O et al. Albumin-bound basal insulin analogues (insulin detemir and NN344): comparable time-action profi les but less variability than insulin glargine in type 2 diabetes. Diabet. Obes. and Metab. 2007;9:290–299. 6. World IMS Data, September 2009.

Proprietary Name: Levemir®. Scheduling Status: S3 Composition: Insulin detemir 100 units /ml. Indication: Treatment of insulin requiring patients with diabetes mellitus. Registration Number: 38/21.1/0084. For full prescribing information refer to package insert approved by the medicines regulatory authority.

Novo Nordisk (Pty) Ltd. Reg No. 1959/000833/07. PO Box 783155, Sandton 2146. Tel: (011) 202 0500 Fax: (011) 807 7989 www.novonordisk.co.za NN/DUO3817/02/2010ver1

SAJDVD Volume 8, Issue 4

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