Type 2 Diabetes - A Freight Train of Health Burden

Affecting Saskatchewan Youth Dr. Munier Nour

Assistant Clinical Professor

Division of Pediatric Endocrinology

Department of Pediatrics, University of Saskatchewan

Faculty/Presenter Disclosure

• Presenters: Munier Nour

• Relationships with commercial interests: • Advisory board participation for Lilly, OPKO and Pfizer

• Site Primary Investigator for Lilly pharmaceutical trial

CFPC COI: Slide 1

Disclosure of Commercial Support

• Prevention Matters has received financial support from: – Community Action Plan for Children

in the form of an educational grant.

• This program has received in-kind support from the Saskatchewan Prevention Institute in the form of logistical support.

• Potential for conflict(s) of interest: • No conflicts of interest

CFPC COI: Slide 2

Mitigating Potential Bias

• Does not apply

CFPC COI: Slide 3

Objectives

• Establish Type 2 Diabetes (DM2) in Youth is under-recognized and rapidly increasing

• Introduce DM2 in Youth as a ‘New Disease’

• Detail the burden of comorbidities with poor treatment options in youth with DM2

• DM2 in youth disproportionately impacts ethnic/racial minorities, further making durable treatment a struggle

• Underscore the need for effective prevention, investigation and treatment in youth onset DM2

Diabetes Classification • Type 1 Diabetes

• Previously referred to as ‘juvenile’ or ‘insulin dependent’ diabetes

• Autoimmune destruction of insulin producing cells (β-cell) resulting in complete insulin deficiency. Often dramatic.

• Insulin injections mainstay of therapy

• Type 2 Diabetes • Previously referred to as ‘adult onset’ diabetes • Result of gradual development of insulin resistance and

relative insulin deficiency • Initial therapies often oral • Later stages may require insulin

Obesity/Type 2 Diabetes Epidemic

• Global epidemic of obesity, in 2015: • 26.7% of Canadians Obese (BMI>30kg/m²)

• 45.9% of SK Obese

• >75% of SK Overweight (BMI > 25kg/m²)

• DM2 epidemiology mirrors obesity

• DM2 prevalence 9.3% in 2015

• Prevalence estimated to reach >12% by 2025, an increase by 44% over 10 years.

Stats Canada 2015 data

Increasing prevalence of DM2 in SK

• DM2 consecutively increasing in SK

• Disproportionately affecting: • First Nations

community

• Women > Men

Dyck, R. et al. CMAJ 2010; 182:249

FN women

FN men

Non-FN men & women

• Dr. Lillian Chase practiced in Regina, but trained in Toronto at the time of insulin discovery.

• <100 years ago, describes first nations community as immune to developing diabetes.

Type 2 Diabetes in Youth

• Childhood obesity epidemic mirroring adult epidemic • 1/3 children in Canada overweight

• Childhood obesity an independent predictor of adult disease

• First description of DM2 in youth in Canada published in 1992 from Manitoba

• Rapidly increasing incidence in youth since then

• Associated with very poor health outcomes

1) Health Promotion and Chronic Disease Prevention in Canada 2016 2) Dean et al 1992 CMAJ

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Incidence Rates of Non-Type 1 Diabetes in Canada

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Adapted from Amed et al. Diabetes Care 2010

* Reporting Bias

Canadian Pediatric Society Surveillance Study

Dyck, R. et al. Can J Diabetes 2012

Epidemiology of Childhood DM in SK

Epidemiology summary

• Type 2 diabetes is increasing at an alarming rate in SK and in Canada

• Predominantly affecting FN community, with females>males

Diabetes Complications in Youth

A ‘New Disease’

• DM2 in Youth is clinically different from both: • DM1 in children and;

• DM2 in adults

• Disproportionately affects those from disadvantaged backgrounds

• Far worse clinical outcomes

• Treatment options are limited and often poorly effective

• 2017 observational study compared >2000 DM patients <20 years old for outcome differences between DM1 and DM2 patients • 1746 DM1

• 272 DM2

• Measured complications after >5 years duration of diabetes

Dabelea, D. et al. JAMA 2017

• DM2 slightly older, later diagnosis, but similar diabetes duration

• DM2 F>M

• DM2 more ethnic minorities

• DM2 BMI greater

• Mean Glycemic control similar • More on target with DM2

Dabelea, D. et al. JAMA 2017

Socioeconomic Determinants

• Those with DM2: • Less private

insurance

• Lower household income

• Lower education level

Dabelea, D. et al. JAMA 2017

Despite similar disease duration and better BG control: DM2 associated with increased risk of: -Nephropathy -Retinopathy -Neuropathy -Hypertension -Arterial Stiffness

Dabelea, D. et al. JAMA 2017

Adult vs Youth DM2

• Early age of diagnosis of DM2 associated with a much higher standardized mortality ratio (SMR)

Al-Saeed et al. Diabetes Care 2016;39:823

Other co-morbidities

• Youth with DM2 have increased risk of multiple complications/comorbidities: • Microvascular & Macrovascular Complications

• Dyslipidemia

• Non-alcoholic Fatty Liver Disease

• Hypertension

• Primary Renal Disease

• Obstructive Sleep Apnea

• Polycystic Ovarian Syndrome

• Psychosocial concerns (depression, social stigma, etc.)

Treatment available to Youth

1. Lifestyle interventions • This is sometimes very dramatic

2. Metformin – oral insulin sensitizer • Improves weight, improves BG, cardiac

benefit

3. Insulin – improves BG • Weight gain, poor compliance, risk of

hypoglycemia, injection, cardiac neutral

Newer/Older agents lack safety and efficacy data for use in children

• Unlikely to successfully go through clinical trials

Canadian Diabetes Association 2013 Clinical Practice Guidelines

Youth DM2 - Response to therapy • Response & Failure in youth is

poor

• RCT of ~700 DM2 youth treated to “treatment failure” endpoint • Randomized to 3 groups

• 45% had treatment failure, with median failure time of 11.5mo!

• Metformin-Lifestyle not sig different vs Metformin alone

• Rosiglitazone later associated with increased cardiac/death

Zeitler P. et al. NEJM 2012

Review of Saskatoon Pediatric Diabetes Clinic

• Currently, the only pediatric diabetes clinic in the province

• Currently serve >500 children with diabetes under the age of 18 • ~10% with DM2

• Based on Ministry data on pharmacy prescription (unpublished) • We see less than 50% of DM2 diagnosed in children

• Likely many more undiagnosed in the community • See next talk Drs. Jill Bally and Shelley Spurr

• Review completed by Nicole Pendleton, MD candidate

Aims and Methods

Primary aim To determine the predictors of early diabetic nephropathy in children with DM2

Study Design Retrospective chart review

Study Population Children with DM2 followed in the Saskatoon Pediatric Diabetes Clinic

Chart Review Collated data from Diabetes Clinic visits EMR and E-Health between Jan 2014 – July 2017

Results

Subjects 67 children with DM2 met inclusion criteria

Sex 40 (60%) females and 27 (40%) males

Ethnicity 53 First Nations, 2 part FN, 1 part Metis, 10 other*, 1 undocumented

*included other genetic syndromes (i.e. Turner syndrome, Alstrom syndrome, Down Syndrome)

Results

Patient Location - 12 from Saskatoon

- 50 from outside Saskatoon

Distance from Saskatoon Mean distance 258 km (±109) Ranged up to >500 km

**SK nearly same land area as Texas

Results – Patient presentatoin

29 (43%) Symptomatic

16 Polyuria & polydipsia

7 Weight loss

3 Polyuria & polydipsia & weight loss

3 Diabetic Ketoacidosis*

38 (56%) Asymptomatic

6 Acanthosis nigricans noted

5 Medical follow-up

6 Routine Screening

Results

Family History of DM2 55 (82%) Family history of DM2

26 (39%) Both 1st and 2nd degree relatives with DM2

15 (22%) One or more 1st degree relative with DM2

14 (21%) One or more 2nd degree relative with DM2

12 (18%) Unknown* or no recorded family history

Results

• Age at diagnosis 12.7 years (±2.3); Mean duration 27 months (±22) • Range: 7 years to 17 years

• 58 obese (88%); 11 overweight (11%)

• Mean A1C 8.6%(±2.9); 33% had target A1C (i.e. A1C < 7%)

• 17 hypertension (26%)

• 15 suspected or documented nephropathy

• 8 Documented neuropathy; 6 retinopathy; 8 wound infection

• 9 with other complications (obstructive sleep apnea, fatty liver, etc.)

Additional predictors of outcomes

• Data analysis & statistics currently underway

Limitations

Mixed cohort. Retrospective review. Missing data

No capture of dietary & physical activity history

No capture of missed visits, loss to follow-up

Moving forward…

• 100 years ago DM2 did not exist among First nations adults

• 25 years ago DM2 did not exist among First nations children

• The potential health & cost implications are staggering

• DM2 in youth leads to pregnancies affected by diabetes • Genetic anticipation with each subsequent generation

• Early diagnosis of diabetes and complications

• *See talk by Dr. Alan Rosenberg Oct 6 @ 8:30

• Current clinical tools are powerless

Prevention • Community/home engagement required

• Drastic changes are required to change current trajectory

• Tax junk/supplement nutritious food

• Exercise/activity programs • Climate difficult in SK

• School based interventions

• Local pediatric services required

• Future research planned

Acknowledgements

• Dr. Mark Inman, Dr. Tim Bradley, Dr. Roland Dyck

• Nicole Pendleton (MD student)

• LiveWell Pediatric Diabetes Team