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PCOS-Diabetes Connection Preventing Diabetes, Heart Disease & Other Complications Breakout

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PCOS-Diabetes Connection Preventing Diabetes, Heart Disease & Other Complications Breakout Saturday, April 16th, 2016 PCOS Challenge & Thomas Jefferson University PCOS Awareness Symposium Philadelphia PCOS-Diabetes Connection Preventing Diabetes, Heart Disease & Other Complications Breakout Katherine Sherif, MD Professor & Vice Chair, Department of Medicine Director, Jefferson Women’s Primary Care Sidney Kimmel Medical College, Thomas Jefferson University Polycystic Ovary Syndrome • Prevalence is high • Essential to diagnose early to prevent metabolic sequelae • Earlier: Infertility, acne, hirsutism, alopecia • Later: Significant metabolic abnormalities & morbidity • Dyslipidemia, IR/IGT/T2D, hypertension, obesity, fatty liver • Obstructive sleep apnea • Eating disorders • Endometrial carcinoma, dysfunctional uterine bleeding • Miscarriages, preterm births, stillbirth, gestational diabetes PCOS: a reproductive disorder • Oligomenorrhea, amenorrhea • Infertility (50 – 60% of all infertility in the US) • Pregnancy loss (30-50%), preterm and stillbirths • Polycystic ovaries • Endometrial carcinoma? • Gestational diabetes (30% GD are PCOS) • …with hirsutism, acne and weight gain Cardiometabolic Disorder • Elevated blood pressure 50% • Abnormal glucose metabolism 50-70% • insulin resistance, IFG, IGT, diabetes • Abnormal lipids 70% • High triglycerides, low HDL-C • Obesity 40-80% • Sleep apnea ? • Fatty liver ? J Intern Med 1996, 239:105–110, J Clin Epidemiol 1998, 51:415–422 Obesity Trends* Among U.S. Adults BRFSS, 1990, 1999, 2008 (*BMI 30, or about 30 lbs. overweight for 5’4” person) 1990 1999 2008 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Obesity Trends* Among U.S. Adults BRFSS, 1985 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% Obesity Trends* Among U.S. Adults BRFSS, 1986 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% Obesity Trends* Among U.S. Adults BRFSS, 1987 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% Obesity Trends* Among U.S. Adults BRFSS, 1988 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% Obesity Trends* Among U.S. Adults BRFSS, 1989 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% Obesity Trends* Among U.S. Adults BRFSS, 1990 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% Obesity Trends* Among U.S. Adults BRFSS, 1991 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% Obesity Trends* Among U.S. Adults BRFSS, 1992 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% Obesity Trends* Among U.S. Adults BRFSS, 1993 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% Obesity Trends* Among U.S. Adults BRFSS, 1994 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% Obesity Trends* Among U.S. Adults BRFSS, 1995 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% Obesity Trends* Among U.S. Adults BRFSS, 1996 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% Obesity Trends* Among U.S. Adults BRFSS, 1997 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% ≥20% Obesity Trends* Among U.S. Adults BRFSS, 1998 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% ≥20% Obesity Trends* Among U.S. Adults BRFSS, 1999 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% ≥20% Obesity Trends* Among U.S. Adults BRFSS, 2000 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% ≥20% Obesity Trends* Among U.S. Adults BRFSS, 2001 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% ≥25% Obesity Trends* Among U.S. Adults BRFSS, 2002 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% ≥25% Obesity Trends* Among U.S. Adults BRFSS, 2003 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% ≥25% Obesity Trends* Among U.S. Adults BRFSS, 2004 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% ≥25% Obesity Trends* Among U.S. Adults BRFSS, 2005 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Obesity Trends* Among U.S. Adults BRFSS, 2006 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Obesity Trends* Among U.S. Adults BRFSS, 2007 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Obesity Trends* Among U.S. Adults BRFSS, 2008 (*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% Bagels 20 Years Ago Today 3-inch diameter 6-inch diameter 140 calories 350 calories 210 calories! 30 French Fries 20 Years Ago Today 2.4 ounces 6.9 ounces 210 calories 610 calories 400 calories! 31 Soda 20 Years Ago Today 6.5 ounces 20 ounces 85 calories 250 calories 165 calories! 32 Coffee 20 Years Ago Today Coffee, 8 ounces Mocha coffee, 16 ounces (with whole milk & sugar) (with steamed whole milk & mocha syrup) 45 calories 350 calories 305 calories! 33 Muffins 20 Years Ago Today 1.5 ounces 4 ounces 210 calories 500 calories 290 calories! 34 Pepperoni Pizza 20 Years Ago Today 500 calories 850 calories 350 calories! 35 Popcorn 20 Years Ago Today 5 cups 11 cups 270 calories 630 calories 360 calories! 36 Larger portions add up 100 extra 10 pound calories per day weight gain per year Maintaining a healthy weight is a balancing act Calories In = Calories Out 37 Definition of Insulin Resistance • Pancreas releases insulin in response to meal • Small peak of insulin and fuel enters cells • IR – cells are resistant to the action of insulin • More insulin required to metabolize meal • Hyperinsulinemia 4 Surefire Ways to Increase Insulin Resistance 1. Eat more 2. Eat more simple carbohydrates 3. Gain weight* 4. Don’t move *Thin people can be insulin resistant Parallel epidemics of diabetes and obesity 1994 2004 Diabetes <4% 4%–4.9% 5%–5.9% >6% Obesity (BMI ≥30 kg/m2) 10%–14% 15%–19% 20%– 24% >25% CDC. www.cdc.gov. Strategies to improve insulin sensitivity • Improve nutrition: • Decrease calories • Change the type of calories • Physical activity: both aerobic & weight training • Insulin sensitizing supplements • Omega-3 fatty acids, vitamin D, magnesium SHOP ON THE EDGES OF THE SUPERMARKET! Weight gain and/or androgens cause adiopose tissue hypertrophy, followed by release of adipokines and inflammatory mediators that cause insulin resistance, weight gain and androgen excess Poli Mara Spritzer et al. Reproduction 2015;149:R219-R227 © 2015 Society for Reproduction and Fertility Pathophysiology Weight gain Larger adipocytes Hyperinsulinemia Insulin resistance in muscle Insulin Receptor Substrate-1 gene mutation (G972R) IRS-1 is in muscle cells and adipocytes Pathophysiology: Reproduction Weight gain Hyperinsulinemia Insulin resistance IRS-1 mutation ↑ Testosterone Irregular menses Infertility Pathophysiology: Metabolic Weight gain Hyperinsulinemia ↑ Blood pressure Insulin resistance ↑ Triglycerides, ↓ HDL β –cell dysfunction IRS-1 mutation ↑ Coagulation Obesity Acanthosis nigricans Traditional treatment does not address cardiometabolic issues ovary ovary endothelium testosterone hyperinsulinemia endothelial dysfunction cysts acne, hirsutism, alopecia dyslipidemia anovulation diabetes Overweight hypertension infertility Acanthosis nigricans Sherif 2006 © “I can’t be insulin resistant, my sugar is fine.” • After years of being insulin resistant…. • Beta cells in the pancreas die • Now the pancreas cannot produce enough insulin to metabolize nutrients and get them into the cells • The blood sugar is high (because the sugar is in the blood, not in the cells of the body as fuel) • You are told you are diabetic….. How do we prevent becoming diabetic? • Keep the pancreatic beta cells happy • Become insulin sensitive so the beta cells don’t have to work as hard • How do you become insulin sensitive? Key: improve insulin sensitivity • Nutrition • Decrease both calories & simple carbohydrates • Increase physical activity and muscle mass • Sleep 8 hours per night – treat sleep apnea • Insulin-sensitizing medications • Insulin-sensitizing supplements Key: improve insulin resistance • Nutrition • Decrease both calories & simple carbohydrates • Increase physical activity and muscle mass • Sleep 8 hours per night • Insulin-sensitizing medications • Insulin-sensitizing supplements Metformin • Benefits: • Weight loss (minimal) • Improved lipid profile • Improved acne, hirsutism and alopecia • Normalization of transaminases • Ovulation & pregnancy • Cochrane meta-analysis: first-line agent for anovulation • Side effects • Gastrointestinal: diarrhea, nausea • Decreased B-12 absorption and homocysteine Lord, BMJ, 2003 Insulin sensitizers improve metabolic & reproductive problems ovary ovary endothelium testosterone hyperinsulinemia endothelial dysfunction cysts acne, hirsutism, alopecia dyslipidemia anovulation diabetes Overweight hypertension infertility Acanthosis nigricans Sherif 2006 © Supplements with insulin-sensitizing properties • Cinnamon • Vitamin D • Chromium 250mg TID • N-acetyl cysteine 500mg • Alpha lipoic acid • Resveratrol • D - chiro inositol & myo-inositol Summary of Management 1. Nutrition counseling & increase physical activity 2. Metformin for metabolic abnormalities 3. Consider supplements 4. Hormonal contraception for dermatologic problems 5. Screen early for • Type 2 diabetes – A1c • Fatty Liver - transaminases • Hypothyroidism – TSH, free T4 • Sleep apnea – STOP BANG • Depression .
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