Effects of Exercise and Physical Activity on Diabetes Mellitus and Obesity

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2 EXERCISE IS MEDICINE: The Science Behind the Movement Effects of Exercise and Physical Activity on Diabetes Mellitus and Obesity Rosa Allyn G. Sy, MD, FPCP, FPSEDM Endocrinology, Diabetes, Metabolism and Nutrition 2

3 FNRI, NNHES

4 BMI BMI > 30 Overweight Obesity % 2.6% 3.2% 4.9% 5.2% 6.8%

5 Abdominal Fat is Bad Fat producing ADIPOCYTOKINES TNF- Lipoprotein Lipase hypertension Angiotensinogen Inflammation Insulin resistance Adipsin FFA Dyslipidemia IL-6 Atherosclerosis Adiponectin PAI-1 Thrombosis Lactate Resistin Leptin Glucose intolerance

6 Pathophysiology OF Obesity and Diabetes Mellitus VISCERAL ACQUIRED CONDITIONS Insulin resistance GENES OBESITY TYPE 2 DM CVD Duvnjak, L & Duvnjak, M. J Physiol Pharmacol

7 Pathophysiology of Metabolic Syndrome Kirk, EP & Klein, S. J Clin Hypertens 2009

8 The Link between physical inactivity and chronic metabolic diseases like diabetes mellitus and obesity is well established; Regular physical activity has important benefits that can be applied to all persons with and without diseases. 8

9 GENERAL BENEFITS OF EXERCISE Cardiorespiratory Health Metabolic Health Musculoskeletal health Regulates weight 9

10 BENEFITS OF EXERCISE STRONG EVIDENCE LOWER RISK OF HYPERTENSION LOWER RISK OF DYSLIPIDEMIA LOWER RISK OF TYPE 2 DM LOWER RISK OF METABOLIC SYNDROME PREVENTION OF WEIGHT GAIN WEIGHT LOSS IMPROVED CARDIORESPIRATORY AND MUSCULAR FITNESS LOWER RISK OF BREAST AND COLON CANCER PREVENTION OF FALL REDUCED DEPRESSION 10

11 BENEFITS OF EXERCISE MODERATE TO STRONG EVIDENCE LOWER RISK OF DEATH LOWER RISK OF CORONARY HEART DISEASE LOWER RISK OF STROKE BETTER FUNCTIONAL HEALTH ( FOR OLDER ADULTS) REDUCED ABDOMINAL OBESITY WEIGHT MAINTENANCE AFTER EIGHT LOSS BETTER COGNITIVE FUNCTION 11

12 BENEFITS OF EXERCISE MODERATE EVIDENCE LOWER RISK OF HIP FRACTURE LOWER RISK OF LUNG CANCER LOWER RISK OF ENDOMETRIAL CANCER INCREASED BONE DENSITY IMPROVED SLEEP QUALITY 12

13 Death Rate (per 10,000) Effect on Mortality of Low Exercise Activity : 13, 344 healthy men and women followed for 8 years Low physical fitness is associated with increased mortality men Women FITNESS LEVEL (LOW TO HIGH) Blain SN et al. JAMA 1989;262:

14 POTENTIAL MORTALITY REDUCTION WITH LIFESTYLE / DIETARY CHANGES ESTIMATED MORTALITY RISK REDUCTION CAD Patients General Population (Primary Prevention) Smoking cessation 35% 50% Physical activity 25% 20 30% Moderate alcohol 20% 15% Combined dietary changes 45% 15 40% 14

15 Lifestyle Intervention in the Prevention of Diabetes Mellitus Study Duration Intervention Results Da Qing 6 years Diet / Exercise/ D + E DPP 2.8 years Diet, PA, BM/ Metformin DPS 3.2 years Intensive Lifestyle XENDOS 4 years Lifestyle / Lifestyle + orlistat 31% 46% 42% 58% 31% 58% 45% 52% 15

16 Does exercise training improve insulin sensitivity? Is this effect of exercise independent of weight loss? Insulin Sensitivity 16

17 Regulation of Muscle Glucose Uptake Glucose Delivery Transport Phosphorylation Glucose 6-phosphate David Wasserman 17

18 Effect of Intervention (%) Mitochondrial Remodeling induced by Moderate- Intensity Exercise predominant effect to increase surface area of the inner mitochrondrial membrane and ETC activity rtdna CS SDH Ubiquinol oxidase CL NADH oxidase 18

19 Insulin Sensitivity (Clamp Log10M) (mg/min-kg FFM ) Relationship between Insulin Sensitivity and Muscle Associated Triglyceride Concentration Changes in muscle lipid metabolism induced by WL + EX Fasting RQ IMCL Size of Lipid Droplets R=0.69, P<0.05 Skeletal muscle Associated Triglyceride ( mol/g wet weight of tissue) Pan D. A. S Lillioja, AD Kriketos, et al Skeletal muscle triglyceride 19 Levels are inversely related to insulin action Diabetes

20 DMCL (% area lipid) Increased IMCL in Athletes However oxidative capacity is also greatly enhanced in muscle of trained individuals Lean Obese Type 2 DM Trained 20

21 Untrained healthy muscle Metabolically inflexible Altered mitochondria? Reduced strength/endurance insulin resistance Untrained healthy muscle Metabolically less flexible basal mitochondria basal strength/endurance basal insulin sensitivity

22 Acute-single bout of exercise Insulin independent glucose uptake Enhanced insulin sensitivity Increased GLUT4 expression 22

23 Untrained healthy muscle Trained muscle Metabolically less flexible basal mitochondria basal strength/endurance basal insulin sensitivity 23

24 Resting healthy muscle Input Exercise Exercise muscle GLUT4 AMPK and ERK MeF2 ERK?AMPK activation is an acute response To exercise Trained muscle has increased GLUT4 expression 24

25 Transcription regulation of Metabolic genes Untrained healthy muscle Metabolically less flexible basal mitochondria basal strength/endurance basal insulin sensitivity Input Training Trained muscle MAP Metabolically kinase pathways flexible AMP Increased kinase mitochondria pathways Calcineurin? Ca activated pathways Increased strength/endurance Enhanced insulin sensitivity Signaling pathways Transcription factors GLUT4 Genes DGK PGC1 25

26 Red Quadriceps GLUT4 (Arbitrary Units) Resistance training increases GLUT4 protein and restores high-fat diet-induced impairments to insulin signaling Control Control RXT Control HF HF-RXT Krisan AD et al. J Appl Physiol 96:

27 THE SCIENCE BEHIND MOVEMENT AND EXERCISE INCREASE BLOOD CIRCULATION INCREASE OXIDATIVE CAPACITY OF THE MUSCLES INCREASE NUMBERS OF MITOCHONDRIA INCREASE ACTIVITY OF MITOCHONDRIA IMPROVES INSULIN SENSITIVITY RELEASE ENDORPHINS 27

28 As exercise training results in marked mitochondrial biogenesis, the question then arises as to why The such ultimate a potent medicine goal is to is not prevent the disease before it occurs more commonly prescribed in clinical practice? Booth FW et al,j Appl Physiol 93: 3-30,

29 29 THANK YOU GOOD DAY