The Obesity/Diabetes Epidemic: Perspectives, Consequences, Prevention, Treatment

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The Obesity/Diabetes EpidemicPerspectives,
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

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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-CDCs diabetes prevention program and
  other Evidence-Based Interventions-
• Basics,
• Next Lecture in Series

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Obesity leads to Prediabetes and Diabetes
Mellitus-Type 2
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Each unit increase in BMI (about 2.7 - 3.6 kg)
increases Type 2 diabetes risk by 12.1 percent
68 - 72 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 146214,1997
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Relationship Between BMI and Risk of Type 2
Diabetes Mellitus
Chan J et al. Diabetes Care 199417961. Colditz
G et al. Ann Intern Med 1995122481.
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Relationship Between Weight Gain in Adulthood and
Risk of Type 2 Diabetes Mellitus
Willett et al. N Engl J Med 1999341427.
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Obesity, Insulin Resistance, Metabolic Syndrome
and the Natural History of Type 2 Diabetes
Age 0-15 15-40 15-50 25-70
Envir. Other Disease
Genes
Macrovascular Complications
Disability
IRS/Metabolic Syndrome ObesityHypertension?HDL,?T
G, Ins. Res.,HYPERINSULINEMIA Endothelial
Dysfunction, AtherosclerosisPCO,ED
Obesity (visceral) Poor Diet Inactivity
Insulin Resistance
MICVAAmp
ppggt140 (7.8mM)
DEATH
IGT Type 2 DM
? ?-Cell Secretion
BlindnessAmputationCRF
EyeNerveKidney
ETOHBPSmoking
Risk of Complications
Disability
Microvascular Complications
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Genes that Cause or are Associated with Diabetes

Insulin action Insulin receptor
PPARG
Insulin Secretion Neonatal KCNJ11/Kir6.2
ABCC8/Sur1 Insulin MODY HNF-1a,1ß, 4
a Glucokinase PDX1/IPF1 Neurod1/Beta2 KLF11 CEL Mi
tochondrial diabetes Type 2
CDKAL1 TCF7L2 HHEX/IDE SLC30A8/ZNT8
WFS1 NOTCH2-ADAM30
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 36324,2339.
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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
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Type 2 Diabetes Two Principal Defects Overview
Abn. first
peripheral
hepatic
1st 2nd
Interactions will NOT occur if B-cells not
genetically predisposed
Reaven GM. Physiol Rev. 199575473-486 Reaven
GM. Diabetes/Metabol Rev. 19939(Suppl
1)5S-12S Polonsky KS. Exp Clin Endocrinol
Diabetes. 1999107 Suppl 4S124-S127.
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prediabetes
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Impaired Glucose Tolerance is Highly Prevalent
Among Obese Youth
Impaired GTT
Diabetes
Normal GTT
GTT glucose tolerance test
Sinha et al. N Engl J Med 2002346802.