Physical activity, type II diabetes, and metabolic syndrome: prevention and intervention 1 糖尿病定義我國衛生署, WHO, ADA  糖尿病    空腹至少8 小時靜脈血漿糖值≧126 mg/dl 75 公克口服葡萄糖耐量試驗(oral glucose tolerance test, OGTT)，2 小時的靜脈血漿糖值 ≧200 mg/dl 前期糖尿病(prediabetes)   空腹血糖異常(impaired fasting glucose, IFG): 空腹血漿糖值110-126 mg/dl 葡萄糖耐量異常(impaired glucose tolerance, IGT): OGTT2小時靜脈血漿糖值140-200 mg/dl 2 3 Key defects in onset of hyperglycemia in Type II DM     ↑Hepatic glucose production ↓insulin secretion ↓insulin action Insulin resistance: suppressed or delayed response to insulin   Usually due to defect in cells that respond to insulin, rather than insulin production Pivotal pathophysiological defects: Insulin resistance in muscle and liver, beta-cell failure Teixeira-Lemos, 2011 Exercise/insulin activate GLUT-4 (glucose transporter-4) translocation 4 5 葉曉文, 2011 6 葉曉文, 2011 7 葉曉文, 2011 8 葉曉文, 2011 9 Definition of metabolic Syndrome   National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III) if 3 out of the following 5 criteria  Central obesity 腰圍       Europe/US: ≥ 94 cm (male) or ≥ 80 cm (female) Taiwan: ≥ 90 cm (male) or ≥ 80 cm (female) HDL < 40 mg/dl (male) or < 50 mg/dl (female) Triglycerides > 150 mg/dl fasting glucose > 100 mg/dl blood pressure > 130/85 mmHg Worldwide prevalence of metabolic syndrome Desroches, 2007 10 11 Definition of metabolic syndrome in children: International Diabetes Federation 12 Lakka, 2007 13 Physical activity in etiology of MetS Lakka, 2007 Obesity and diabetes 37,878 women, 6.9 years follow-up Weinstein, 2004 14 15 PA and diabetes Weinstein, 2004 16 Energy expenditure and diabetes Weinstein, 2004 17 Walking and diabetes Weinstein, 2004 18 PA, obesity and diabetes Weinstein, 2004 19 PA, obesity and diabetes Weinstein, 2004 PA, obesity and diabetes need to combine PA and weight loss Weinstein, 2004 20 21 PA, obesity, and risk for DM Hu, 2007 22 PA, fasting glucose, and risk for DM Hu, 2007 PA, fasting glucose, obesity, and risk for DM Hu, 2007 23 24 Bassuk, 2005 25 Bassuk, 2005 ProActive Trial 26 Physical activity measured by accelerometry 30-50 yr, low PA, follow-up 1 year Simmons, 2008 Moderate PA reduce fasting insulin Physical activity measured by accelerometry Ekelund, 2009 27 28 Vigorous PA and MetS Lakka, 2007 PA intensity and type II diabetes Insulin Resistance Atherosclerosis Study, n=1625, 1992-94 29 Vigorous:  6 METs Mayer-Davis EJ, 1998 30 PA intensity and type II diabetes Insulin Resistance Atherosclerosis Study, n=1625, 1992-94 Vigorous:  6 METs Mayer-Davis EJ, 1998 31 2-wk interval training in obese men  4-6 30s Wingate/session, 6 sessions Whyte, 2010 32 2-wk interval training in obese men Whyte, 2010 33 Change in PA and Type II DM Lakka, 2007 34 Increase PA, decrease DM risk Hu, 2007 Finnish Diabetes Prevention Program: 3234 at-risk, 2.8 years follow-up Church, 2011 35 36 Lifestyle (exercise) prevent MS Orchard, 2005 37 Lifestyle (exercise) prevent MS Orchard, 2005 38 Exercise training and insulin resistance Church, 2011 39 MONET study 137 overweight/obese postmenopausal women MONET: Montreal–Ottawa New Emerging Team Karelis, 2008 40 MONET study 137 overweight/obese postmenopausal women Karelis, 2008 MONET study 6 mo. caloric restriction/resistance exercise 41 42 MONET study 6 mo. caloric restriction/resistance exercise Drapeau, 2011 43 The HERITAGE Family Study   investigate the contribution of regular exercise to changes in risk factors for cardiovascular disease and Type 2 diabetes genetics of cardiovascular, metabolic, and hormonal responses to exercise training    ages of 17 and 65 yr healthy but sedentary 20-wk aerobic exercise training program PA decrease risk factors in those already having MetS Katzmarzyk, 2003 44 PA decrease number of risk factor in those already having MetS Katzmarzyk, 2003 45 PA decrease number of risk factor in high-risk subjects Katzmarzyk, 2003 46 Type II DM and reactive oxygen species (ROS)  oxidative stress secondary to hyperglycaemia and hyperlipidaemia occurs before the appearance of clinical manifestations of late diabetes complications    suggesting a key role in the pathogenesis of the disease. Insulin resistance and pancreatic b-cell dysfunctionare modulated by ROS ROS disrupt insulin-induced cellular redistribution of insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K), impairing insulin-induced glucose transporter type 4 (GLUT4) translocation in 3T3-L1 adipocytes Teixeira-Lemos, 2011 47 48 Type II DM and inflammation  dyslipidaemic phenotype of diabetes: ↑TG, ↑ oxidized LDL, ↓HDL    fat cells produce adipocytokines (adipokines)   lipotoxicity profile of diabetes Lack of exercise leads to accumulation of visceral or deep subcutaneous adipose stores, leads to large adipocytes that are resistant to insulin-evoked lipolysis suppression, resulting in ↑release of FFA and glycerol go to muscle, liver and arterial tissue, where exert deleterious effects on metabolism and vascular function Adipose tissue of obese and type 2 diabetic individuals is infiltrated by mononuclear cells and Teixeira-Lemos, 2011 is in a state of chronic inflammation 49 Type II DM and inflammation  The adipocytes and infiltrated macrophages secrete pro-inflammatory/pro-thrombotic cytokines    TNF-a, IL-6, resistin, adipsin, acylationstimulating protein (ASP), plasminogen activator inhibitor 1 (PAI-1) and angiotensinogen promote atherogenesis and cause insulin resistance Low adiponectin in type II DM  a potent insulin-sensitizing and anti-atherogenic adipokine Teixeira-Lemos, 2011 Exercise prevent Type II DM antioxidant and anti-inflammation Teixeira-Lemos, 2011 50 Exercise prevent Type II DM antioxidant and anti-inflammation Teixeira-Lemos, 2011 51 Exercise prevent Type II DM antioxidant and anti-inflammation Teixeira-Lemos, 2011 52 Exercise prevent Type II DM antioxidant and anti-inflammation Teixeira-Lemos, 2011 53 Exercise prevent Type II DM antioxidant and anti-inflammation Teixeira-Lemos, 2011 54 55 PA and prevention of MetS     Intervention studies show that exercise training has a mild or moderate favorable effect on many metabolic and cardiovascular risk factors that constitute or are related to the MetS favorable lifestyle changes, including regular physical activity, are effective in the prevention of type 2 diabetes in individuals with overweight and impaired glucose tolerance ↑total volume of moderate-intensity PA, maintain good cardiorespiratory and muscular fitness appears to markedly decrease the risk for MetS, especially in high-risk groups Brisk walking > 30 min/day Lakka, 2007 American Diabetes Association/ACSM Position Statement     56 Exercise plays a major role in the prevention and control of insulin resistance and type 2 diabetes Both aerobic and resistance training improve insulin action and can assist with glucose levels, lipids, BP CV risk, mortality, and QOL Exercise MUST be undertaken regularly to have continued benefits Most persons with type 2 diabetes can perform exercise safely with certain precautions Colberg, 2010 Consensus in Insulin Resistance in Children        lack of a clear cutoff to define insulin resistance in children childhood weight gain increase the risk of insulin resistance in children Insulin resistance is a risk factor for prediabetes and T2D in childhood Exercise and fitness improve insulin sensitivity through weight loss and also mechanisms independent of weight loss in adolescents PA increases insulin sensitivity, an important component of any intervention weight gain velocity during childhood is associated with lower insulin sensitivity in adulthood prevention strategies should be started early in life  lifestyle interventions should be included, whereas metformin should be limited to selected cases Levy-Marchal,2010 57 58 Telford 2007