Topic 07-Diabetes-S_2011

Topic 07-Diabetes-S_2011 - 7. Diabetes & The Metabolic...

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Click to edit Master subtitle style 7. Diabetes & The Metabolic Syndrome A. What are they? B. Critical issues C. Pathogenesis of the MS D. Molecular events leading to diabetes
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First: a disclaimer n These lectures will deal with topics with which many in our society are very sensitive n Whatever you thought you knew: forget n Approach this topic with an open mind n Take nothing personally 2 2
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Why will this be our only n Diabetes & obesity are epidemics n They are related n Collectively: The metabolic syndrome n #1 issue for future health care providers n Causes are much more complex 3 3 Obesity Diabetes (type 2)
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Obesity defined by BMI n Waist size or waist : hip ratio better measure for 4 4 n Body mass index , WHO classification n BMI=mass (kg)/height (m)2 n Empirical classifications based on clinical outcomes n Perhaps not appropriate for individuals ¨ Muscle mass (average Buffalo Saber: 26.7) ¨ Not all fat tissue is Underweight (<18.5) Healthy (18.5- 24.9) Overweight (25- 29.9) Obese (>30) Morbidly obese (>40)
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Diabetes is defined by blood n Normal ¨ 70-110 mg/dL fasting ¨ <140 mg/dL after OGT n Diabetic ¨ >125 mg/dL fasting ¨ >200 mg/dL after OGT 5 5 Diabeti c Norm al IGT IFG
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Treatment of obesity n Morbidly obese: Surgery n Less Obese: Pharmacologica l (?) n Overweight: ¨ Lifestyle ¨ Diet 8 8 Pharmacotherapy BMI>5 0 BMI>4 0 BMI>3 0 Surgery Diet Physical Activity Lifestyle Modification
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The questions 1. Why the increase in BMI? 2. Why is it difficult to lower BMI 3. How does obesity progress to type 2 diabetes? 4. What is the metabolic derangement of type 2 diabetes 12 12
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Origins of the obesity epidemic n Not as simple as “ moral hazard” ¨ eat too much ¨ move too little n What has changed since 1985? n . Energy IN (food) n Why? ¨ Biological/environmental 13 13
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Many factors with unknown 14 14 http://www.shiftn.com/obesity/Full-Map.html
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Many factors with uncertain 15 15 Energ y Balan ce Energy in: quantity& quality Energy out Neurophysiology: Individual Social Physiology: Genetics Microbial (GI) Maternal
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Why is it so difficult to reduce n Short term: easy n 2-year period: Very hard ¨ Food abundance is recent ¨ Human evolution n Starvation imminent n Resistance to starvation selective advantage 16 16
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To increase stores: Ein>Eout 17 17 Intak e Expenditur e Restore Balance Stores=stab le
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To decrease stores: 18 NOT WHAT HAPPENS!
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The issue: “Energy homeostasis is regulated to defend the highest weight achieved”* 19 *JO Hill (2006).   Endocrine Reviews 27 (7):750-761 Energy IN & b Larger Stores b Energy IN & b Involuntary p Energy OUT Protect energy stores against starvation
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2 Adipose prolifera tion Mechanistic n DIET: Decreasing intake ¨ Leptin normal ¨ . Insulin ¨ . Satiety ¨ . Ghrelin n CNS: x pushes intake n NYP/AgRP Rules ¨ . Intake & stores ¨ . Energy output ¨ . Number adipose cells 20 20 Satiet y peptid Insuli n Lepti n NPY/Ag RP neuron s POMC /CART . E intake . E stores Ghreli n Pleasure/reward system h E out . E stores
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New insulin sensitive adipocytes n Balance is restored n The stores were defended!
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Topic 07-Diabetes-S_2011 - 7. Diabetes &amp; The Metabolic...

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