1. The Obesity/Diabetes Epidemic: Perspectives, Consequences, Prevention, Treatment
Part 5
Stan Schwartz MD, FACP, FACE
Private Practice, Ardmore
Obesity Program
Cardiometabolic Diabetes Center and Affiliate,
Main Line Health System
Emeritus, Clinical Associate Professor
University of Pennsylvania

2. Outline Epidemiology and Economics of obesity/diabetes
Perspectives on Obesity
Consequences of Obesity, Prediabetes, Obesity
Obesity/ Diabetes Risk Factors,
Obesity/ Diabetes Onset can be Prevented or Delayed – Early Risk Identification and Intervention.
Medical Benefits to Weight Loss
Treatment-CDC’s diabetes prevention program and other Evidence-Based Interventions-
Basics,
Next Lecture in Series

3. Obesity leads to Prediabetes and Diabetes Mellitus-Type 2

4. Each unit increase in BMI (about 2. 7 - 3
Each unit increase in BMI (about kg) increases Type 2 diabetes risk by 12.1 percent
% of diabetes risk in the U.S. is attributable to or associated with excess weight
For every kilogram increase in weight over 10 years, Type 2 diabetes risk increases 4.5 %
Ford et al. Amer J Epidemiol 146:214,1997

5. Relationship Between BMI and Risk of Type 2 Diabetes Mellitus
Age-Adjusted Relative Risk
Body Mass Index (kg/m2)
<23
24–24.9
25–26.9
27–28.9
33–34.9 25 50 75
100
1.0
2.9
4.3
5.0
8.1
15.8
27.6
40.3
54.0
93.2
<22
23–23.9
29–30.9
31–32.9
35+
1.5
2.2
4.4
6.7
11.6
21.3
42.1
Men
Women
The risk of diabetes increases with increasing BMI values in men and women [1,2]. Moreover, the age-adjusted relative risk for diabetes begins to increase at BMI values that are considered normal for men (24 kg/m2) and women (22 kg/m2) based on mortality risk. The marked increase in the prevalence of obesity is an important contributor to the 25% increase in the prevalence of diabetes in the United States over the last 20 years [3]. Increases in abdominal fat mass, weight gain since young adulthood, and a sedentary lifestyle are additional obesity-related risk factors for diabetes [1,4,5].
1. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med 1995;122:
2. Chan JM, Rimm EB, Colditz GA, et al. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 1994;17:
3. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, Diabetes Care 1998;21:
4. Ohlson LO, Larsson B, Svardsudd K, et al. The influence of body fat distribution on the incidence of diabetes mellitus. Diabetes 1985;34:
5. Helmrich SP, Ragland DR, Leung RW, Paffenbarger Jr RS. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 1991;325:
Chan J et al. Diabetes Care 1994;17:961.
Colditz G et al. Ann Intern Med 1995;122:481.

6. Obesity, Insulin Resistance, Metabolic Syndrome and the Natural History of Type 2 Diabetes
Age
Envir.+ Other Disease
Genes
Macrovascular Complications
Obesity (visceral)
Poor Diet Inactivity
IRS/Metabolic Syndrome
Obesity HypertensionHDL,TG,
Ins. Res.,HYPERINSULINEMIA
Endothelial Dysfunction, Atherosclerosis PCO,ED
Disability
Insulin Resistance
MI CVA Amp
ppg>140 (7.8mM)
IGT Type 2 DM
DEATH
 -Cell Secretion
Blindness Amputation CRF
Eye Nerve Kidney
Risk of Complications
ETOH BP Smoking
Disability
Microvascular Complications

7. Genes that Cause or are Associated with Diabetes
Insulin Secretion
Neonatal KCNJ11/Kir6.2
ABCC8/Sur1
Insulin
MODY HNF-1α,1β, 4 α
Glucokinase
PDX1/IPF1
Neurod1/Beta2
KLF11
CEL
Mitochondrial diabetes
Type 2
CDKAL1
TCF7L2
HHEX/IDE
SLC30A8/ZNT8
WFS1
NOTCH2-ADAM30
Insulin action
Insulin receptor
PPARG
PHENOTYPE-
eg: age of
presentation,
IFG/ IGT/Both/
severity
depends on number of
which kind of genes
a person inherits –
GENOTYPE
Obesity
FTO
MCR4
Unknown
IGFBP2
CDKN2A/B
KIF11
JAZF1
CDC123-CAMK1D
TSPAN8-LGR5
THADA
ADAMTS9
NOTCH-ADAM30
Modified from McCarthy, NEJM 363:24,2339.

8. The Adipocytokine Syndrome: A New Model for Insulin Resistance and ß-Cell Dysfunction
Atherothrombosis
Liver
Artery
CRP, PAI-1
FFA, TNFa, IL-6
Angiotensinogen, PAI-1
FFA, TNFa
Obesity IR
Diabetes
ASVD
Adiponectin
Adiponectin
FFA
Visceral
fat cells
Resistin, TNFa
Leptin
Sns
FFA, TNFa, Leptin
Muscle
Brain
Pancreas

9. prediabetes

11. Impaired Glucose Tolerance is Highly Prevalent Among Obese Youth
Normal GTT
Impaired GTT
Diabetes
Age 11–18 y
75%
21% 4%
Age 4–10 y
75%
25%
Although the prevalence of type 2 diabetes is increasing, only a small percentage of obese children have this disease. However, impaired glucose tolerance is highly prevalent in obese children and adolescents. Among a multiethnic cohort of 167 children and adolescents recruited from a pediatric obesity clinic, about 25% had abnormal glucose tolerance tests, and 4 of 112 adolescents had frank diabetes [1]. Those with impaired glucose tolerance had higher BMI than those with normal glucose tolerance. Impaired glucose tolerance was present in Hispanic, non-Hispanic black, and non-Hispanic white children.
1. Sinha R, Fisch G, Teague B, et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 2002;346:
GTT: glucose tolerance test
Sinha et al. N Engl J Med 2002;346:802.