Natural History of Obesity Leading to Type 2 Diabetes Complications Onset of diabetes Disability Genetic susceptibility Environmental factors Nutrition Physical inactivity Obesity Insulin resistance IGT Ongoing hyperglycemia Death IGT = Impaired Glucose Tolerance Risk for Disease Metabolic Syndrome Atherosclerosis Hyperglycemia Hypertension Retinopathy Nephropathy Neuropathy Blindness Renal failure CHD Amputation

Obesity Trends. Among U. S Obesity Trends* Among U.S. Adults (BMI ≥ 30 or ≈ 30 lbs overweight for 5’4” woman) F as in Fat: How Obesity Policies Are Failing in America. Trust for America’s Health Issue Report. October 2004.

Prevalence (%) of overweight among children and adolescents Average 11 year old boy today is 11 pounds heavier than in 1973 This graph shows how childhood overweight has tripled since the 1960s. The epidemic of childhood obesity is a particular concern because it predicts much suffering from health problems starting at an earlier age than previously. It is estimated that this will be the first generation in the US to have a shorter lifespan than their parents.

National Longitudinal Survey of Youth Prospective Cohort Study of 8270 Children (4-12 years old) - 1999 Risk of Overweight Overweight > 85th %ile BMI > 95th %ile BMI African American 38.4% 21.5% Hispanics 37.9% 21.8% Caucasian 25.8% 12.3% Showing that prevalence rates vary by ethnicity. Source: NHANES???

Secular Increases in Relative Weight and Adiposity in Children (5-14 years old) - Bogalusa Heart Study - Study years Weight (kg) Height (cm) BMI (kg/m2) 1973-1974 35.9 140 17.6 1992-1994 41.0 142 19.5 Change* +3.4 +1.6 +1.5 * Change adjusted for height, age, race, and sex Source: Pediatrics 99:420-426, 1997

Correlations of Weight and BMI in Youth at 7.7 and 23.6 Years Source: Minneapolis Children’s BP Study, Circulation 99:1471, 1999

Relationship Between Prevalence of Overweight and Daily TV Hours Gortmaker et al., 1996

Overweight Children Ate fewer fruits and vegetables (2.9 vs. 3.3/day) Drank more sweetened beverages (1.3 vs. 1.1/day) Ate more high-fat snacks (64 vs. 56 %; p=0.054) Ate more fast food (1.4 vs. 1.1/week; p=0.051) Spent more screen time (101 vs. 81 minutes) Less likely take part in lessons on nutrition (50 vs. 64 percent). Special Report on Policy Implications from the 1999 California Children’s Healthy Eating and Exercise Practices Survey. The California Endowment. Rev. August 2002.

Pediatric Overweight AAP Policy Statement Identify and track at risk youth Calculate and plot BMI yearly Promote health eating patterns Fruits, vegetables, low-fat dairy, whole grains Self-regulation of intake, limits on choices, modeling Promote physical activity Limit TV and video Monitor changes in obesity-associated risk factors (BP, lipids, IGT, apnea, hyperinsulinism) AAP = American Academy of Pediatrics Source: Pediatrics 112, August 2003

Metabolic Syndrome Prevalence in 12-19 Year Olds Overall 4.2% (6.1% M, 2.1% F) BMI  95th percentile 28.0% BMI 85th-94th percentile 6.8% BMI < 85th percentile 0.1% Based on 1994 population estimates, 910,000 adolescents had metabolic syndrome. Source: Cook et al., Arch Pediatr Adolesc Med 157:821-827, 2003

Link Between Obesity and Type 2 Diabetes: Nurses’ Health Study

Number of Bariatric Surgeries 1992-2003 Surgery for Severe Obesity: US 1992 to 2003 NEJM March 11, 2004

GI Surgery for Severe Obesity Risk and Complications: 10-20% require follow-up surgery Abdominal hernia Break down of staple line Gallstones 30% develop nutritional deficiency Cost: $20,000 to $50,000 Source: NIDDK Highest Increase Rate of all Pediatric Surgeries

Natural History of Obesity Leading to Type 2 Diabetes Complications Onset of diabetes Disability Genetic susceptibility Environmental factors Nutrition Physical inactivity Obesity Insulin resistance IGT Ongoing hyperglycemia Death IGT = Impaired Glucose Tolerance Risk for Disease Metabolic Syndrome Atherosclerosis Hyperglycemia Hypertension Retinopathy Nephropathy Neuropathy Blindness Renal failure CHD Amputation

Type 2 Diabetes A Progressive Disease Impaired glucose tolerance (IGT) Undiagnosed diabetes Known diabetes Insulin resistance Insulin secretion Postprandial glucose Fasting glucose Microvascular complications Macrovascular complications Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789

Burden of Diabetes in USA 18.2 Million Americans Have Diabetes 5.2 Million Unaware of Diagnosis 40 Million Americans Have Prediabetes 239,000 Diabetes-Related Deaths/year 2-to-6-Fold More Likely to Have Heart Disease 2-to-4-Fold More Likely to Have a Stroke 75% of All Diabetes Related Deaths Associated With Cardiovascular Disease Cost $132 Billion/2002 Mokdad, et al, JAMA 2001 286,1195

Diabetes and Gestational Diabetes Trends Among Adults in the United States, Behavioral Risk Factor Surveillance System, 1990, 1995 and 2001 1990 1993 2001

Prevalence of Diabetes

Diabetes Prevalence Among Minority Populations in the U.S. Percentage of each population with diabetes Non-Hispanic Whites Latinos African Americans 7.8% (11.4 million) 10.2% (2 million) 13% (2.8 million) 15.1% (105,000)  Native Americans & Alaska Natives Centers for Disease Control and Prevention (CDC) 1999 www.cdc.gov/diabetes

Age Specific Prevalence of DM 2002

The Changing Face of Diabetes in Youth 5 10 15 20 25 30 35 % with type 2 87 88 89 90 91 92 93 94 95 96 Cincinnati <19 years Little Rock 8-21 years San Antonio <19 years Source: Fagot-Campagna et al., J Pediatr 136:664-672, 2000

Diabetes Projected Risks: For Babies Born in 2000 Girls: 38% lifetime risk If diabetic before age 40, Lifespan shortened by 14 years (Quality of life by 19 years) Boys: 33% lifetime risk If diabetic before age 40, Lifespan shortened by 12 years. (Quality of life by 22 years) V Narayan et al: JAMA 8 Oct 2003

Prevalence of Diabetes in Pregnancy in the United States of America 8% Non-diabetes 92% More than 135,000 GDM + 200,000 T2DM + 6,000 T1DM pregnancies annually American Diabetes Association. Diabetes Care. 1998;21(Suppl. 2).

Major Birth Defects: Preexisting Type I vs Type II Diabetes

ADA Goals for Glycemic Control A1C < 7.0%* Pre-prandial plasma 90-130 mg/dl glucose Peak postprandial <180 mg/dl plasma glucose *Referenced to a non-diabetic range of 4.0-6.0% using a DCCT-based assay

Diabetes Care in the U.S. Improvement Needed Data from NHANES III* and BRFSS** Participants 18-74 years with DM Results: Percent at Goal A1C < 7.0 43% (>9.5, 18%) LDL < 100 11% (>130, 58%) BP < 140/90 66% Dilated eye exam 63% Foot exam 55% * Nat’l Health & Nutrition Exam Survey ** Behavioral Risk Factors Surveillance Study

Majority of Patients with Diabetes are Not at ADA HbA1c Goal <7%

Census Bureau Projections 2000-2050 Census Bureau projects population will grow 47% by 2050 By 2050, there will be 112% more diagnosed cases of diabetes Serious diabetes complications are projected to increase 137-189% by 2050 Diabetes 50 (Suppl 2): A205, 2001

GLOBAL PROJECTIONS FOR THE DIABETES EPIDEMIC: 2003-2025 (millions) World 2003 = 194 million 2025 = 333 million Increase 72%

Age Adjusted Prevalence of CVD 1997-2002

End Stage Renal Disease 1984-2001

Coronary Heart Disease Mortality in Type 2 Diabetes Men Women 60 60 Diabetes Diabetes 50 50 No Diabetes No Diabetes 40 40 Mortality Rate per 1000 Mortality Rate per 1000 30 30 20 20 10 10 0-3 4-7 8-11 12-15 16-19 20-23 0-3 4-7 8-11 12-15 16-19 20-23 Duration of Follow-up (yr) Duration of Follow-up (yr) Krowlewski AS, et al Am J Med 1991; 90 (suppl2A):56S-61S.

A1C Predicts CV Risk in Type 2 Diabetes Kuusisto et al 229 Finnish Patients Followed for 3.5 Years CHD mortality All CHD events Incidence (%) over 3.5 years 5 10 15 20 25 5 10 15 20 25 † * Low <6% Middle 6.0%–7.9% High >7.9% Low <6% Middle 6.0%–7.9% High >7.9% A1C tertile CHD=coronary heart disease *P<0.01 vs lowest tertile; †P<0.05 vs lowest tertile Kuusisto J et al. Diabetes. 1994;43:960-967

UKPDS - Glycemic Control Risk Reductions Lancet 1998; 352: 837-853

UKPDS - BP Control Risk Reductions Any Diabetes Related Endpoint Deaths Related to Diabetes 24% Risk Reduction 32% Risk Reduction Events/ 1000 pt-years p=0.0046 p=0.0019 n=1148 UKPDS. BMJ 1998 317: 703-713

4S Study: Effect of Simvastatin on Coronary Events - 6 years Diabetic Patients n=201, p=0.002 Nondiabetic Patients n=4242, p<0.00001 55% Risk Reduction 32% % of Patients with a Major Coronary Event Pyorala et al, Diabetes Care 1997; 20: 614

Incidence of diabetes reduced 58% (p=.0003). Prevention of T2D with Lifestyle Intervention (N=523 with IGT, mean age 55, BMI 31) Weight Loss (kg) Cases 1st year 2nd year 4th year Intervention* -4.2 -3.5 26 (10%) Control** -0.8 57 (22%) Incidence of diabetes reduced 58% (p=.0003). * diet, exercise, frequent visits ** yearly advice Source: Tuomilehto et al., ADA 2000

Type 2 Diabetes Prevention Percent developing diabetes All participants All participants Risk reduction 31% by metformin 58% by lifestyle Placebo 40 30 Metformin Cumulative incidence (%) 20 Lifestyle 10 1 2 3 4 Years from randomization The DPP Research Group, NEJM 346:393-403, 2002

School-based Program to Decrease Soda Consumption 644 children (7-11 years old), 6 schools Program to decrease regular and diet soda intake delivered in 1-hour sessions 4 times per year # Glasses of Soda Per Day % Overweight and Obese Intervention  0.6  0.2 Control  0.2  7.5 Source: James et al., Brit Med J 328:1237, 2004

Natural History of Obesity Leading to Type 2 Diabetes Complications Onset of diabetes Disability Genetic susceptibility Environmental factors Nutrition Physical inactivity Obesity Insulin resistance IGT Ongoing hyperglycemia Death IGT = Impaired Glucose Tolerance Risk for Disease Metabolic Syndrome Atherosclerosis Hyperglycemia Hypertension Retinopathy Nephropathy Neuropathy Blindness Renal failure CHD Amputation