Prediabetes: A Key to Curbing the Diabetes Epidemic

Michael E. Bowen, MD, MPHAssistant Professor Internal Medicine, Pediatrics, Clinical Sciences

Divisions of General Internal Medicine, General Pediatrics, and Outcomes and Health Services ResearchDedman Family Scholar in Clinical Care

University of Texas Southwestern Medical Center, Dallas, TX

Disclosures

Dr. Bowen has no financial interests or other relationships with commercial concerns directly

related to this program. Dr. Bowen will be discussing off-label uses of medications.

Objectives

• Define prediabetes

• Identify patients at risk for diabetes and prediabetes

• Describe evidence-based treatments and interventions for prediabetes

• Identify resources and develop strategies to improve the management of your patients with prediabetes

What is Prediabetes?• Glucose levels that are higher than normal, but not

high enough to be diagnosed as diabetes– Umbrella term including impaired fasting glucose and

impaired glucose tolerance

• Precursor to diabetes– Asymptomatic condition diagnosed in the process of

being tested for diabetes

• “Risk factor” for diabetes vs. a clinical entity– Topic of vigorous debate

– Bottom line• Diabetes risk increases across the glucose continuum

• Prediabetes is a high-risk glucose state at increased risk for developing diabetes

Natural History of Type 2 Diabetes

Figure courtesy of the AACE Diabetes Resource Center

Fasting glucose

Type 2 diabetes

Years from

diagnosis0 5–10 –5 10 15

Prediabetes

Onset Diagnosis

Postprandial glucose

Macrovascular complications

Microvascular complications

Insulin resistance

Insulin secretion

-Cell function

Summary: Hyperglycemia in Prediabetes and Diabetes

• Hyperglycemia results from a combination of:

–Beta-cell dysfunction Impaired insulin secretion

– Increased hepatic glucose production due to excessive glucagon

–Decreased uptake of peripheral glucose due to insulin resistance

Diabetes Care. 2013; 36, Suppl 2:127-138.

Diagnosis

Normal

Impaired Fasting Glucose

Diabetes

Normal

Impaired Glucose Tolerance

Diabetes

Normal

Prediabetes

Diabetes

Fasting Glucose

2 hour Glucose on OGTT

Hemoglobin A1C

100 mg/dL

126 mg/dL

140 mg/dL

200 mg/dL

5.7%

6.5%

Prediabetes

• Agreement between tests is poor• 7.7% of population has Prediabetes by BOTH A1c and fasting glucose criteria• 4.9% have Prediabetes by A1c criteria alone• 20.5% have PDM by fasting glucose but not A1C

• High variance in fasting glucose and 2 hour glucose values – confirm abnormal testsDiabetes Care. 2015;38 Suppl 1: S8-16. Diabetes Care. 2010;33 (10):2190-2195.

Diabetes is Just the Tip of the Iceberg!

NCDC and Prevention. National Diabetes Statistics Report, 2014. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf.

MMWR Morbidity and Mortality Weekly Report. 2013;62:209-212.

29 Million with Type 2 Diabetes (9.3% of the

Population)

86 Million with Prediabetes (37% of the Population)

77 Million of those with Prediabetes are UNDIANOSED

Change in US Prevalence: 2007-2010

0

20

40

60

80

100

120

140

2007 2012

57

86

17.9

29

5.7

8.1

Pe

op

le (M

illio

ns)

Undiagnosed Diabetes

Diagnosed Diabetes

Prediabetes

Diabetes: 9.3% of Population

Prediabetes: 37% of Population

CDC and Prevention. National diabetes fact sheet, 2007. http://www.cdc.gov/Diabetes/pubs/pdf/ndfs_2007.pdf.

CDC and Prevention. National Diabetes Statistics Report, 2014. http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf.

Projecting the Future Burden of Diabetes

7.8

3.3

22.9

14.7

8.4

Estimated that 1 in 3 US adults will develop DM in

their lifetime

Boyle et al. Population Health Metrics 2010,8:29.

200-300% Increase in Prevalence (2010-2050)

Curbing the Diabetes Epidemic

Non-modifiable Risk Factors

• Age

• Family history

• Race/Ethnicity

Modifiable Risk Factors

• Overweight/obesity

• Hypertension

• Physical inactivity

• Abnormal lipid metabolism

• Prediabetes/elevated glucose levels

• Recognition and Modification of Risk Factors• Diagnosis and treatment of Prediabetes

Diabetes Care. 2014;37(suppl 1):S14-S80.

Case 1: Screening

Mrs. D is a healthy, 44 year old nulliparous African American female presenting for an annual exam. Her BP is 129/76 and BMI is 26 kg/m2. She takes no medications and does yoga 2 days per week and attends a spinning class at the YMCA 3 days per week. She has no family history of diabetes. Her lipid panel from today’s visit is pending. Diabetes screening is recommended based on which of the following risk factors:

A. Age

B. BMI

C. Physical inactivity

D. Race

E. Age and Race

F. BMI and Race

G. None of the above – screening is not indicated

Diabetes Screening Guidelines

• American Diabetes Association (and revised USPSTF)– All adults over age 45– BMI ≥ 25 (or ≥ 23 in Asians) and ANY of:

• Non-white race Hypertension• HDL<35 or TG >250 Family history• PCOS Baby > 9# or gestational DM• Cardiovascular disease Physical inactivity• Prediabetes

• Recommended Screening AND Diagnostic tests:– Hemoglobin A1C, Fasting glucose, Oral Glucose Tolerance Test

• Repeat screening every 3 years if normal– Annually if prediabetes

Diabetes Care. 2014;37(suppl 1):S14-S80.

Diabetes Screening

• Proactive diabetes screening

– Only 50% of eligible patients screened

• Prediabetes is ONLY identified through diabetes screening

– Improved diabetes screening is critical to:

• Diabetes detection

• Prediabetes detection

• Diabetes prevention

http://www.clinicalendocrinologynews.com/news/news/single-article/only-half-of-at-risk-adults-being-screened-for-diabetes/d23d462bfa6c020ddf93a82cd08c3d2e.html

Random Glucose as Opportunistic Screening?

• Random glucose is routinely tested– 95% of glucose tests in clinical practice are random

• Role for random glucose in screening is poorly defined

• Diagnosis: Random glucose≥ 200 mg/dL in the setting of polyuria/polydipsia

• What about random glucose values < 200mg/dL?

Diabetes Care. 2004;27:9-12. Diabetes Care. 2014;37(suppl 1):S14-S80

Random Glucose as a Diabetes Risk Factor?

Glucose Criteria Undiagnosed Pre-DM Undiagnosed DM

Random Glucose≥100mg/dL 3.3 (3.0, 3.8) 31.2 (21.3, 45.5)

RBG≥100mg/dL (Adjusted)* 2.4 (2.0, 2.7) 20.4 (14.0, 29.6)

Results Stratified by Random Glucose Level

Random glucose <100 mg/dL* Reference Reference

Random glucose 100-119 mg/dL* 2.2 (1.9, 2.5) 7.1 (4.4, 11.4)

Random glucose 120-139 mg/dL* 3.29 (2.6, 4.2) 30.3 (20.0, 46.0)

Random glucose ≥140 mg/dL* 3.5 (2.2, 5.5) 256.0 (150.0, 436.9)

Results presented as weighted odds ratios

*Adjusted for age, sex, race, BMI, HTN, HLD, CVD, FH Diabetes

J Clin Endocrinol Metab. 2015; http://press.endocrine.org/doi/abs/10.1210/jc.2014-4116

Case 1: Screening

Mrs. D is a healthy, 44 year old nulliparous African American female presenting for an annual exam. Her BP is 129/76 and BMI is 26 kg/m2. She takes no medications and does yoga 2 days per week and attends a spinning class at the YMCA 3 days per week. She has no family history of diabetes. Her lipid panel from today’s visit is pending. Diabetes screening is recommended based on which of the following risk factors:

A. Age

B. BMI

C. Physical inactivity

D. Race

E. Age and Race

F. BMI and Race

G. None of the above – screening is not indicated

Risks Associated with Prediabetes

• Increased risk for diabetes1,2

– Approximately 25% develop diabetes over 3-5 years

• Increased risk of cardiovascular disease1,2,3,4

• Increased risk of chronic kidney disease2,4

• Increased risk of neuropathy2,4

• Increased risk of Retinopathy1,2

• Increased risk of cancer5

– Liver, endometrial, stomach, colorectal

1Diabetes Care; 2007; (39(3). 753-759 2Endocrine Practice. 2008; 14(7):933-946. 3N Engl J Med.2010; 362(9): 800-811. 4J Am Coll Cardiol. 2012; 59: 635-643. 5Diabetologia. 2014; 57(11): 2261-2269.

What is the Evidence?

LIFESTYLE MODIFICATION AND DIABETES PREVENTION

Case 2: Prediabetes TreatmentMrs. K, a 46 year old Hispanic female with a BMI of 29 kg/m2, was recently diagnosed with prediabetes (fasting glucose 109 mg/dL and A1C 6.1%). Which of the following evidence based interventions should you recommend?

A. Metformin

B. Lifestyle intervention with goal 7% weight loss

C. Acarbose

D. Orlistat

E. Metformin + Lifestyle

Diabetes Prevention Program (DPP)• 1996-1999: randomized controlled trial• Multicenter trial (n=27) that enrolled 3,234 patients

without DM– BMI ≥ 24 kg/m2 (≥ 22 kg/m2 in Asians)– Fasting plasma glucose 95-125 mg/dL or 2H post prandial

glucose 140-199 mg/dL

• Randomized to:– Standard lifestyle + placebo– Standard lifestyle + metformin (started 850mg QD; increase to

850mg BID at 1 month) – Intensive lifestyle intervention

• Primary outcome: Diabetes (diagnosed by annual OGTT or twice yearly fasting plasma glucose)– Mean Followup: 2.8 years

N Engl J Med. 2002;346:393-403.

DPP: Lifestyle Intervention

• Intensive intervention– Goal 7% weight loss

• 25% of calories from fat

• 1200-1800 kcal/day goal based on initial body weight

– >150 minutes of physical activity each week• Intensity target: brisk walking

• At least 700 kcal/week

– Individualized, one-on-one 16 lesson curriculum over 24 weeks• Monthly individual and group sessions to reinforce

changes

N Engl J Med. 2002;346:393-403.

DPP: Baseline DemographicsCharacteristic DPP Study Population

(N=3234)

Age, year (SD) 50.6 (10.7)

Female sex, % 67.7

Race

White, % 54.7

African American, % 19.9

Hispanic, % 15.7

Asian, % 4

Family History of diabetes, % 69.4

BMI 34 (6.7)

Fasting plasma glucose 106.5 (8.3)

2 hour glucose (OGTT) 164.6 (17.0)

A1C, % 5.91 (0.50)

DPP: Diabetes IncidenceStudy Arm Crude DM Incidence/100

person yearsRelative Risk Reduction

Placebo 11% Reference

Metformin 7.8%* 31% (17-43)

Lifestyle Intervention 4.8%* 58% (48-66)

*P<0.001 vs. placebo

N Engl J Med. 2002;346:393-403. Circulation: Cardiovascular Quality and Outcomes.i 2009;2:279-285. DynaMed Weekly Update. 2014; 8(47).

Study Arm Cumulative DM Incidence at 3 y

Number Needed to Treat (3 years)

Placebo 28.9% ----

Metformin 21.7% 13.9 (5.4-9.5)

Lifestyle Intervention 14.4% 6.9 (5.4-9.5)

Statins: Primary CAD Prevention: 5-year NNT = 108 assuming 7.5% 10-year baseline riskAspirin: Primary CAD Prevention: 5-year NNT > 300

DPP: Goal Attainment in the Lifestyle Intervention

At 24 weeks At End of Study

Weight loss > 7% 50% 38%

Exercise > 150 minutes/week

74% 58%

N Engl J Med. 2002;346:393-403. 2Diabetes Care. 2006; 29.2012-2017.

• For every 1 kg in weight loss, a 16% reduction in diabetes risk over 3 years2

• Adjusted for changes in diet and activity

Changes in Weight, Activity, and Med Adherence

Mean Weight LossPlacebo: 0.1 kg

Metformin: 2.1 kgLifestyle: 5.6 kg

N Engl J Med. 2002;346:393-403.

DPP: Subgroup Analyses

• Subgroup analyses, underpowered

– Age, sex, race, BMI, fasting and 2H glucose levels

• Lifestyle Intervention – effective in all subgroups

– More effective if lower 2 hour OGTT glucose

• Metformin

– More effective at BMI ≥ 35 kg/m2

– Fasting glucose 110-125 mg/dL

N Engl J Med. 2002;346:393-403.

Lifestyle Modification and DM Prevention – Additional Trials

Study N Intervention Primary Outcome: Relative Risk Reduction

DPP (2002)1 3324 Diet+Exercise 58% at 2 years

Finnish DPS (2001)2

522 Diet+Exercise 58% at 3 years

Da Qing (1997)3, 4

577 Diet/Exercise/Diet+Exercise 51% at 6 years

Indian DPP (2006)5

531 Diet+exercise 28.5% at 2.5 years

1N Engl J Med. 2002;346:393-403. 2N Engl J Med. 2001;344:1343-1350. 3 Lancet.2008;371:1783-1789. 4Diabetes Care. 1997;20:537-544. 5Diabetologia. 2006;49(2):289-297.

Case 2: Prediabetes TreatmentMrs. K, a 46 year old Hispanic female with a BMI of 29 kg/m2, was recently diagnosed with prediabetes (fasting glucose 109 mg/dL and A1C 6.1%). Which of the following evidence based interventions should you recommend?

A. Metformin

B. Lifestyle intervention with goal 7% weight loss

C. Acarbose

D. Orlistat

E. Metformin + Lifestyle

Case 3: Long Term Treatment Effects

You recommended lifestyle modification with at least a 7% weight loss goal for Mrs. K based on the findings from the DPP. At 1 year, she successfully loses 6% of her body weight and has a fasting glucose of 95 mg/dL and an A1C of 5.7%. Twelve months later she has regained 10 pounds and has a fasting glucose of 109 mg/dL and an A1C of 6.0%. What is her 10 year risk of developing diabetes?

A. Unchanged compared to baseline riskB. Lower risk by virtue of reverting to normal

glycemia over the past yearC. Higher risk because she has shown she cannot

sustain her weight loss goals

Diabetes Prevention: Long Term Impact of Lifestyle Intervention?

Study N Intervention Followup Relative Risk Reduction

DPP (2002)1 3324 Diet+Exercise 10 years 24%

Finnish DPS (2001)2

522 Diet+Exercise 7 years 43%

Da Qing (1997)3

577 Diet+Exercise 20 years 43%

1Lancet. 2009;374:1677-1686. 2Lancet. 2006;368(9548):1673-1679. 3 Lancet.2008;371:1783-1789. 4Lancet. 2012;379:2243-2251.

• DPP4 – Participants going from prediabetes to normal glucose regulation at least once during the study had a 56% lower risk of diabetes over 10 years

— Reversion to normal glucose tolerance associated with younger age, weight loss, intensive lifestyle intervention

Case 3: Long Term Treatment Effects

You recommended lifestyle modification with at least a 7% weight loss goal for Mrs. K based on the findings from the DPP. At 1 year, she successfully loses 6% of her body weight and has a fasting glucose of 95 mg/dL and an A1C of 5.7%. Twelve months later she has regained 10 pounds and has a fasting glucose of 109 mg/dL and an A1C of 6.0%. What is her 10 year risk of developing diabetes?

A. Unchanged compared to baseline riskB. Lower risk by virtue of reverting to normal

glycemia over the past yearC. Higher risk because she has shown she cannot

sustain her weight loss goals

What is the Evidence?

PHARMACOLOGIC TREATMENT AND DIABETES PREVENTION

Case 4: Medications for Prediabetes

Mr. R is a 58 year old Caucasian male with a history of coronary artery disease. He is overweight (BMI 37 kg/m2), a smoker, and has hypertension and high cholesterol. He has severe peripheral vascular disease that limits his exercise. His fasting glucose is 117 mg/dL and his A1C is 6.3%. Which of the following medications is FDA approved to treat his prediabetes?

A. MetforminB. AcarboseC. Pioglitazone D. OrlistatE. All of the aboveF. None of the above

Medication RCTs for Diabetes Prevention

Study N Duration Medication Dose/day Relative Risk Reduction

Side Effects

DPP1 3324 3 y Metformin 1700mg 31% GI

IDPP2 531 2.5 y Metformin 500mg 26% GI

Stop NIDDM3

1429 3 y Acarbose 300mg 25% GI

ACT NOW4 602 2 y Pioglitazone 45mg 72% Weight gain,edema

DREAM5 5269 3 y Rosiglitazone 8 mg 60% CHF, weight gain

CANOE6 207 4 y Rosiglitazone + Metformin

4mg1000 mg

66% diarrhea

1N Engl J Med. 2002;346:393-403 2Diabetologia. 2006;49(2):289-297 3Lancet. 2002;359(9323):2072-2077. 4N Engl J Med. 2011;346:1104-1115. 5Lancet. 2006;368(9541):1096-1105. 6Lancet. 2010;376(9735):103-111.

Cardiovascular and Long Term Outcomes with Medications

• Acarbose (STOP-NIDDM Trial) may improve cardiovascular outcomes1

– 49% relative reduction (2.5% absolute risk reduction) in CV events

– Caveat: Study powered for diabetes incidence, not CVD (Only 84 events)

• 1.4% per year (placebo) vs. 0.7% per year (Acarbose)

1JAMA. 2003;290(4):486-494

What is the Durability of Medication Effects for Diabetes prevention?

• Most medications effects do no persist after discontinued

• Metformin is exception: 25% reduction after 2-week washout period2

• Relevance of this is unclear

1JAMA. 2003;290(4):486-494. 2Diabetes Care. 2003;6:977-980.

Weight loss Medications and Diabetes Prevention

• No adequately powered RCTs examining weight loss drugs and diabetes prevention

• Eligibility for weight loss medication1

– Failed weight loss goals by lifestyle alone

– BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with weight related complications

– Not pregnant, seeking pregnancy, nursing

1Obesity. 2013;22:S5-S39.

Weight Loss Medications and Diabetes Prevention

• Orlistat – lipase inhibitor– XENDOS1 – 4 year double blind placebo-controlled RCT powered to

detect progression to diabetes– Lifestyle + Orlistat 120mg TID vs. Lifestyle + placebo

• Included subjects with BMI≥30 kg/m2 and normal (79%) or IGT (21%)• 52% completion rate

– 36% risk reduction for incident diabetes (p=0.003)• Underpowered to examine conversion from preDM to DM

• Phentermine/Topiramate ER (Qsymia)– Subgroup analysis of Phase 3 Trial – underpowered– Phentermine/Topiramate ER vs. Placebo– 7.5 mg/46mg dose: 49% risk reduction – 15mg/92mg dose: 89% risk reduction– Greater weight loss, greater reduction in diabetes incidence

• greatest benefit ≥15% weight loss

1Diabetes Care. 2004;27:155-161. 2Diabetes Care. 2014;37:912-921

Medications for Diabetes Prevention: Summary

• No medications are currently FDA approved for treatment of prediabetes or diabetes prevention

• Thiazolidinediones– concerns about long term cardiovascular safety

• Acarbose– safe, but up to 40% discontinuation for GI side effects

• Orlistat– Safe, but use limited by GI side effects (up to 90% of

patients have GI side effects)

Diabetes Care 2015;38(Suppl1)S313-32.

Metformin – Off Label Recommendations in Prediabetes

• Recommendations based on the safety, tolerability, and efficacy relative to other medication options

• American Diabetes Association

– BMI > 35 kg/m2

– Age < 60

– Prior gestational diabetes

Diabetes Care 2015;38(Suppl1)S313-32.

Summary: Prediabetes Treatment

• Lifestyle modification

– Goal 5-10% weight loss

– Moderate intensity physical activity (approximately 30 minutes per day or 150 minutes per week)

• Metformin

– Off label use based on Diabetes Prevention Program findings

• Age < 60

• BMI > 35 kg/m2

• Prior gestational diabetes

Case 4: Medications for Prediabetes

Mr. R is a 58 year old Caucasian male with a history of coronary artery disease. He is overweight (BMI 37 kg/m2), a smoker, and has hypertension and high cholesterol. He has severe peripheral vascular disease that limits his exercise. His fasting glucose is 117 mg/dL and his A1C is 6.3%. Which of the following medications is FDA approved to treat his prediabetes?

A. MetforminB. AcarboseC. Pioglitazone D. OrlistatE. All of the aboveF. None of the above

Translating Evidence into Practice

Setting Goals with Your Patients

• Goals should be set by patients– Nutrition/dietary goal– Physical activity goal

• Partner with– Nutritionists– Wellness Coaches

• Healthcare team– Discuss goals with patient– Facilitate success– Provide support

• S – SpecificSimple and clear

• M – MeasurableKey to reaching goal

• A – AttainablePick goals you can reach

• R – RelevantPick goals important to you

• T – Timely Beginning and end

Characteristics of Successful Lifestyle Intervention Programs

• Intensive: small group or one-on-one for 6 –12 months

• Extended: > 2 years contact duration

• Multi-component– Reduced total caloric intake, reduced fat intake

– Exercise

– Increased fiber intake

• Well integrated behavioral principles

• Moderate weight loss: – 5-7% weight loss

– 3-4% long-term weight loss maintenance

Implementing the DPP Lifestyle Intervention in the Community

• DEPLOY (Diabetes Education & Prevention with a Lifestyle Intervention Offered at the YMCA

– Pilot Study at 2 YMCAs

• Randomized 92 participants

• Group Lifestyle vs. control (brief counseling)

– Eligibility:

• BMI ≥ 24 kg/m2 and ≥ 2 diabetes risk factors

• Random capillary glucose 110-199 mg/dL

Am J Prev Med. 2008;35:357-363.

DEPLOY: Outcomes

• Outcome at 4-6 months

Am J Prev Med. 2008;35:357-363.

Outcome Control (n=38) Intervention (n=38) P value

% weight loss -2% (-3.3, -0.6) -6% (-7.3, -4.7) <0.001

% BMI decrease -2.3% (-3.7, -0.8) -5.8% (-7.3, -4.4) 0.001

Change in Total Cholesterol

+6 mg/dL (-2.8, 14.8) -21.6 mg/dL (-29.2, -13.3) <0.001

• Effects sustained after 12 months• No differences by race and gender

YMCA Diabetes Prevention Program

• Community-based study based on DPP lifestyle intervention– Offered at 7 DFW YMCAs

• 12 month program– 16 one-hour weekly sessions

– Monthly small group session with lifestyle coach

• Program Goals– Lose 7% body weight

– Goal 150 minutes/week physical activity

http://www.ymcadallas.org/healthy_living/health_well-being__fitness/diabetes_prevention/

“Prevent Diabetes STAT”• CDC and AMA initiative

– Free toolkit to guide screening and referral

– Fact sheets

– Risk assessment tools

– Referral letters

– In-clinic flow process to identify high risk patients

– Logic for EMR query to identify at risk patients

• Online risk assessment for patients

http://www.ama-assn.org/sub/prevent-diabetes-stat/index.html

Diabetes Prevention and the ACA

• ACA eliminated out of pocket fees for preventative services (New commercial/individual health plans (September 23, 2010)

• Covers USPSTF “A” or “B” rated recommendations

• INCLUDES:– Diabetes screening (Currently only for adults with hypertension)

– Obesity screening

– Nutrition counseling for those at high risk for chronic disease such as diabetes and hypertension

http://intermountainhealthcare.org/ext/Dcmnt?ncid=522452203

ACA CoverageService Service Codes ICD-9 Code

Commercial and Private Insurance

Individual Diet/exercise counseling 99401-99404 278.X (Obesity)250.X (Diabetes)V65.3 (Dietary Counseling)V65.41 (Exercise Counseling)

Medical Nutrition Therapy (dietician) 97802-97804 Varies by plan

Medicare Plans

Intensive Behavioral Therapy for Obesity Month 1: 1 visit/weekMonth 2-6: 1 biweekly visitMonth 7-12: monthly visit only if lose

≥ 3kg at month 6

G0447 V85.30 to V85.39

Medical Nutrition Therapy (dietician) 97082-97084 Only if diabetes, renal disease, or renal transplant past 3 years

Bariatric Surgery Covered if BMI>35 and at least 1 obesity-related comorbidity if previously unsuccessful with medical obesity treatment.

http://intermountainhealthcare.org/ext/Dcmnt?ncid=522452203

Conclusions

• Prediabetes is a strong but modifiable risk factor for developing diabetes

• Early diagnosis and intervention is critical

• Lifestyle modification is the cornerstone of prediabetes treatment

• Insurance coverage is increasingly available for lifestyle modification and behavioral interventions

Questions and Comments

Prediabetes: Historical Perspective

• 1950s: Retrospective diagnosis in pregnancy– Associated with High birthweight baby family history of

diabetes

• 1980s: WHO abolished concept– Many with borderline glucose do not convert to

diabetes

– ‘prediabetic’ label created issues in insurance coverage and ‘false alarm’

• 2002: ADA endorsement of prediabetes term leads to widespread use of the term

Diabetes, Obesity, and Metabolism. 9(Suppl. 1.)2007. 12-18.

Statins and Diabetes Risk• Mild increase in diabetes incidence

– 9% increased risk for incident diabetes1

• Treatment of 255 (95% CI 150-852) patients with statins for 4 years results in 1 case of diabetes

• High-potency statins may increase risk for diabetes more than lower potency statins2

– 15% (95% CI 5-26%) increased risk in first 2 years after statin use for Rosuvastatin/Atorvastatin/Simvastatin (dose > 40mg) compared with all other statins• Retrospective study of patients hospitalized for new CV event

• FDA3 –– “A small increased risk of raised blood sugar levels and the

development of Type 2 diabetes have been reported for the use of statins.”

– “…we think the heart benefit of statins outweighs this small increased risk….but blood sugar levels may need to be assessed after instituting statin therapy.”

1Lancet. 2010; 375(9716): 735-742 2BMJ. 2014; 348:g3244. 3www.fda.gov/ForConsumers/ConsumerUpdates/ucm293330.htm

Antihypertensives and Diabetes Risk

• Thiazides-– RR 0.91 ( 95% CI 0.73-1.13) for incident diabetes

compared with those on no antihypertensive therapy

• Beta Blockers– RR 1.28 (95% CI 1.04-1.57) for incident diabetes

compared with those on no antihypertensives

• No increase in risk with ACE Inhibitors and Calcium Channel Blockers

N Engl J Med. 2000;342:905-912.

DPP

• Estimated number needed to treat over 3 years to prevent 1 case of diabetes

• Lifestyle intervention: 6.9 (95% CI: 5.4-9.5)

• Metformin: 13.9 (95% CI: 8.7-33.9)

• Adverse Events

• No treatment related deaths; no increase in hospitalizations

• Gastrointestinal: Metformin (77.8) vs. Placebo (30.7) events per 100 person years

• Musculoskeletal: Lifestyle (24.1) vs. Placebo (21.1) events per 100 person years