The Diabetes Prevention Program: Call for Action

The Diabetes Prevention Program: Call for Action Osama Hamdy, MD, PhD, FACE Medical Director, Obesity Clinical Program, Director of Inpatient Diabetes Management, Joslin Diabetes Center Harvard Medical School Boston, USA

National Institutes of Health Normal Vision

National Institutes of Health With Cataract Treatable

National Institutes of Health With Glaucoma Treatable

National Institutes of Health With Diabetes?

Diabetes Foot

Ulcer Infection Amputation

Prevalence of Complications is High at Time of Type 2 Diabetes Diagnosis Complication Any complication Prevalence (%)* 50 Retinopathy Abnormal EKG Absent foot pulses ( 2) and/or ischemic feet Impaired reflexes and/or decreased vibration sense Myocardial infarction/angina/claudication Stroke/transient ischemic attack 21 18 14 7 ~2 3 ~1 *Some patients had >1 complication at diagnosis. Adapted from Holman RR. Consultant. 1997;37(suppl):S30-S36. UKPDS. Diabetologia. 1991;34:877-890.

*CDC 2014 There Are 29 Million Patients in the US with Diabetes and 86 Million with Prediabetes*

Behind the Numbers CDC s Division of Diabetes 2014 1 0

Diabetes is a Global Health Crisis IDF Diabetes Atlas, Sixth edition, 2014.

Global Prevalence of Diabetes Projected to More than Double by 2030 Europe 2000: 33 million 2030: 48 million The Americas 2000: 33 million 2030: 67 million Africa and Middle East 2000: 22 million 2030: 61 million Asia and Australia 2000: 83 million 2030: 190 million <2% 2%-5% 5%-8% 8%-11% 11%-14% Nationwide Diabetes Prevalence Categories WHO. Diabetes Action Now. 2004.

Diabetes Cost in the US 18 12 9 8 10 Total estimated cost of diabetes in 2012 was $245 billion (41% up from 2007), with $176 billion direct cost and $69 billion reduced productivity 43 Largest component of medical expenditures attributed to diabetes was hospital inpatient care (~43% of costs) Hospital Antihyperglycemic medications Nursing/residential facility Prescription for diabetes complications Physician office visits Others Diabetes Care. 2013; 36(4): 1033-1046

Blood Glucose >180 mg/dl Cook CE et al. J Hosp Med 2009; 4:E7-E14

$11,858 Patients with diabetes incurred an average of $3337 more in hospital costs $7,830 ICU Non-Critical Care

Why We have More People with Diabetes?

1990 1991 92 1993 94 No data <10% 10 15% 15 20% 20 25% >25% 1995 96 No data <4% 4 6% 6 8% 8 10% >10% 1997 98 1999 2000 2001

Obesity Worldwide

Number of Obese Individuals in the US Obesity in Adults >20 years 40.6 m Women Obesity in Kids 2-19 years Girls Boys 7 m 5.5 m 35% 37.5 m Men 16% Ogden CL et al. CDC/NCHS data brief, no 82. Hyattsville, MD: National Center for Health Statistics. 2012.

The Prevalence of Prediabetes and Type 2 Diabetes in Obese Children & Adolescents 30% 25% TYPE 2DIABETES STARTS TO APPEAR IN CHILDREN 25% 21% 20% 15% 10% 5% 4% 0% Childeren Adolescents Prediabetes Type 2 DM Sinha R et al N Engl J Med 2002;346(11):802-10

Health Risks of Obesity >5x Relative Risk 2-5x Relative Risk 1-2x Relative Risk Type 2 diabetes All-cause mortality Cancer mortality Dyslipidemia (high TG, low HDL) Hypertension Breast cancer Sleep apnea MI and stroke Prostate, esophagus and colon cancer Non alcoholic fatty liver Gout Asthma Hypoventilation syndrome Gallstones GERD PCOS Endometrial CA Osteoarthritis of knees Impaired fertility Anesthetic risk Pancreatitis

Economic Impact of Obesity For 2008, medical costs associated with obesity were estimated at $147 billion. The medical costs for people who are obese were $1,429 higher than those of normal weight. Finkelstein EA et al. Health Affairs. 2009;28:822-831.

90% of patients with newly diagnosed diabetes are overweight or obese 100 80 90% Obese (BMI >30) Diabetes patients with BMI 25 kg/m 2 (%) 60 40 20 60 30 Overweight (BMI 25 30) 0 N = 31,000 aged 18 to 79 years National Health Interview Survey, 2003 Geiss LS et al. Am J Prev Med. 2006;30:371-7.

What is Diabetes?

Relative Function (%) Natural History of Diabetes Obesity IFG / IGT Diabetes Uncontrolled Hyperglycemia 250 200 Insulin Resistance 150 100 50 0-10 -5 0 5 10 15 20 25 30 Years before Diabetes Years of Diabetes -cell Function

Insulin Resistance and Type 2 Diabetes Blood Cell Insulin Glucose

The Closed Loop Cycle of Diabetes & Obesity Weight Gain in a Person with FH of type 2 DM Hypertension More insulin secretion Increased Need for Glucose -cell Exhaustion Type 2 DM -cells Secrete More Insulin Liver, Muscles and Fat Insulin Resistance

Relative Risk of Complications Complications Risk in Diabetes 8 6 4 2 0 Hemoglobin A1c Avg Glucose 6 7 8 9 10 11 12 120 150 180 210 240 270 300 Adapted from: Skyler JS. Endocrinol Metab Clin North Am. 1996 Jun;25(2):243-54. DCCT Study Group. N Engl J Med 329:977, 1993. UKPDS 35. Stratton IM. BMJ 321:405-412, 2000.

Diabetic Complications Microvascular Complications Diabetic Retinopathy Macrovascular Complications Stroke Diabetic Nephropathy Heart Disease Diabetic Neuropathy Peripheral Vascular Disease Harris MI. Clin Invest Med 1995;18:231-239 Nelson RG et al. Adv Nephrol Necker Hosp 1995;24:145-156

Years of life lost Diabetes is Associated with Significant Loss of Life Years 7 6 Men Non-vascular deaths 7 Vascular deaths 6 Women 5 4 3 2 1 5 4 3 2 1 0 0 40 50 60 70 80 90 0 0 40 50 60 70 80 90 Age (years) Age (years). On average, a 50-year-old individual with diabetes and no history of vascular disease will die 6 years earlier compared to someone without diabetes Seshasai et al. N Engl J Med 2011;364:829-41

Body Shape Defines the Risk Apple Below Waist Above Waist Pear Vague J. Am J Clin Nutr. 1956;4:20-34.

Intra-abdominal Fat: The Critical Adipose Depot Subcutaneous Fat Intra-abdominal Fat

How is Pre-diabetes and Diabetes are diagnosed? Category A1C Fasting Plasma Glucose 2-Hour Plasma Glucose in OGTT Normal <5.7 Below 100 mg/dl Below 140 mg/dl Pre-diabetes 5.7% - 6.4% 100-125 mg/dl (IFG) 140-199 mg/dl (IGT) Diabetes 6.5% >126 mg/dl >200 mg/dl American Diabetes Association. Diabetes Care 2011; 34;(Suppl.1):S11-61.

Mortality in Relation to A1C in People without Diabetes: EPIC-Norfolk Study Khaw K T et al. BMJ 2001

Call for Action The Diabetes Prevention Program (DPP)

Change From Baseline (%) WGT, weight; BMI, body mass index; W-H, waist-to-hip ratio; IS, insulin sensitivity. Hamdy O. Diabetes Care. 2003;26:2119-2125. Weight Loss Improves Insulin Sensitivity and May Prevent Diabetes or Reverse it Obese Patients With Insulin Resistance +/ T2D *P<0.001.

How Much Weight Do You Need to Lose? From the 2013 Obesity Guidelines -3.0% -5.0% Decreases risk for developing diabetes Improvements in blood glucose, blood pressure, HDL, and triglycerides -10.0% Greater improvements in above parameters -15.0% Even greater improvements in above parameters Jensen MD, et al. 2013 AHA/ACC/TOS Guideline. J Am Coll Cardiol. 2014;63(25 Pt B):2985-3023.

Diabetes Prevention Program Why Diabetes Prevention Program? Type 2 diabetes affects: 13% of adults older than age 45 About 20% of adults older than age 60 More than 50% of women who have had gestational diabetes More African-Americans, Hispanic-Americans, Asian-Americans and Pacific Islanders, and American Indians than Caucasians

The Diabetes Prevention Program A Randomized Clinical Trial to Prevent Type 2 Diabetes in Persons at High Risk Sponsored by the NIH, NIDDK, NIA, NICHD, IHS, CDC, ADA and other agencies and corporations

Study Interventions Eligible participants Randomized Standard lifestyle recommendations Intensive Lifestyle (n = 1079) Metformin (n = 1073) Placebo (n = 1082)

Lifestyle & Metformin Interventions Intensive Lifestyle Goals Reduction of fat and calorie intake Physical activity at least 150 minutes/week Achieve and maintain at least 7% weight loss Metformin Goals Metformin 850 mg twice daily

Study Timeline 1996 DPP Recruitment Began 1999 DPP Enrollment Completed 2001 DPP Results 2002 DPPOS Began 2009 DPPOS Midpoint Results 2013 DPPOS Visits End 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 June 1996 December 2013

Weight Change (kg) Mean Weight Change 0-2 -4-6 Placebo Metformin Lifestyle -8 0 1 2 3 4 Years from Randomization

MET-hours/week Mean Change in Leisure Physical Activity 8 Lifestyle 6 4 2 Metformin Placebo 0 0 1 2 3 4 Years from Randomization

Cumulative incidence (%) 40 30 20 Percent developing diabetes Incidence of Diabetes Placebo (n=1082) All participants Metformin (n=1073, p<0.001 vs. Placebo) Lifestyle (n=1079, p<0.001 vs. Met, p<0.001 vs. Plac ) Lifestyle Metformin (n=1079, (n=1073, p<0.001 vs. vs. Plac) Metformin, Placebo (n=1082) p<0.001 vs. Placebo) Risk reduction 31% by metformin 58% by lifestyle 10 0 0 1 2 3 4 Years from randomization

Weight Change Over Time

DPPOS Incidence of Diabetes

Summary of DPP Study Lifestyle changes emphasizing weight reduction and increased physical activity are effective in decreasing progression to diabetes in high risk individuals They are also effective in reducing multiple CVD risk factors in people with prediabetes: hyperglycemia, hypertension and dyslipidemia The effects on CVD events is not yet known

How DPP is Conducted?

Keys to Successful Weight Reduction Multidisciplinary Intervention

Strategies for optimal weight loss Aim for 5-10% weight loss and a maintenance of ~7% for long-term Proper Medical Nutrition Therapy (MNT) Caloric level & Dietary Composition Proper Exercise Type Duration Frequency Behavioral Modification SMART Goals Cognitive support Medications Medications that cause weight gain Weight loss medications Meal Replacements Patient adherence and compliance for long-term success

What Worked in the DPP? Reduction of calorie intake and dietary education Physical activity for at least 150 minutes/week (10,000 steps) Group intervention and social interaction Engagement with health coach for adherence Regular follow up for credibility Behvaioral modification Aim for at least 7% weight loss in the first year

Lost in Healthcare: Most Healthcare Providers Spend Between 13-16 Minutes with Each Patient 13-16 Minutes SCHEDULING/ ADMISSION CHECK-IN/ ARRIVAL PRE-VISIT FINANCIAL NAVIGATION CHECK-OUT/ DISCHARGE Patient Access Care Delivery & Care Management Check-Out / Discharge

Digital Health Solutions for DPP

Weight Loss (%) 5-year Results of the Joslin Why WAIT Program 0.0 Duration in Months 0 3M 6M 9M 12M 15M 18M 21M 24M 27M 30M 33M 36M 39M 42M 45M 48M 51M 54M 57M 60M -2.0-4.0-3.5% -6.0-8.0-6.4% -10.0-12.0-14.0 *** *** *** *** *** *** ** * *** *** *** *** *** *** *** *** *** *** *** *** *** -9.0% -16.0 *** p<0.001 (group 1 vs. group 2) Total Group n=129 Group 1 n=61 (Participants maintained <7% weight loss at 1 year) Group 2 n=68 (Participants maintained > 7% weight loss at 1 year) Hamdy O et al. ADA Annual Conference, Boston 2015

Balanced Exercise Model Flexibility Aerobic Strength Stretching Yoga Walking Swimming Biking Dancing Resistance tubing Weight lifting Yoga Strength exercise is particularly important during weight reduction

Why WAIT won the ADA 2015: Michaela Modan Memorial Award

Why WAIT in a Digital Health Application

Expenditures in the Medicare Population With Diabetes Classification of Medicare consumers based on aggregate payments Crisis - Top 1% Heavy- 90 to 99 percentile Moderate - 75 to 89 percentile Light - 50 to 74 percentile Low - Under 49 percentile Caballero AE et al. Am J Manag Care. 2013;19(7):541-548.

Expenditures in the Medicare Population With Diabetes Caballero AE et al. Am J Manag Care. 2013;19(7):541-548.

Cost saving per year Economic Impact of Weight Loss in One Year in Patients With Diabetes Cost Saving (1% wt loss) Estimated Saving with (7% wt loss) (-3.6%) 1* (-5.8%) 2* (-44%) Health Care Cost Diabetes Related Cost (-27%) 1. p<0.05 2. p<0.001 YU AP et al. Curr Med Res Opin. 2007;23(9):2157-69

Take Home Message Diabetes is one of the most costly chronic condition Epidemic of diabetes is growing rapidly due to increased prevalence of obesity Diabetes can be prevented or delayed by lifestyle intervention that leads to 5-10% weight loss Diabetes prevention is one of most cost-effective intervention Diabetes prevention program is now available in several formats including digital health platform A call for action should not be delayed any longer

Thank You