Impact of Exercise on Patients with Diabetes Mellitus

Impact of Exercise on Patients with Diabetes Mellitus Bret Goodpaster, Ph.D. Exercise Physiologist Assistant Professor of Medicine University of Pittsburgh Division of Endocrinology and Metabolism

Learning Objectives After completing this section, you should be able to: 1. Discuss the relative role of physical activity in body weight regulation, i.e., energy balance. 2. Define insulin resistance and describe its role in the development of type 2 diabetes. 3. Compare and contrast the effects of exercise and dieting on body weight, body composition and metabolism. 4. Debate the impact of exercise on glucose control.

Two Main Types of Diabetes Mellitus Type 1 Insulin required to live Ketoacidosis ( Fat metabolism) Weight Loss Average onset = 11 years old Type II Not initially dependent on insulin Insulin resistance/ insensitivity > 80% are overweight Average onset > 40 years

Source: ADA website 2005 Type 2 Diabetes Type 1 Diabetes Results from insulin resistance (a condition in which the body fails to properly use insulin), combined with relative insulin deficiency. Most Americans who are diagnosed with diabetes have type 2 diabetes. Results from the body's failure to produce insulin. It is estimated that 5% 10% of Americans who are diagnosed with diabetes have type 1 diabetes.

Type 2 Diabetes >30 million worldwide ( 18.5 million in the United States) Many individuals do not know they have Type 2 diabetes 90% 95% of all Diabetes mellitus is Type 2 Increasing in incidence in last four decades Population specific (Native Americans, Hispanic, African American)

Risk Factors for Type 2 Diabetes Obesity Age Body fat distribution Family history of diabetes Physical inactivity Race/ethnicity Previous gestational diabetes (GDM) Elevated fasting glucose levels Impaired glucose tolerance

Obesity and Risk of Type 2 Diabetes Age-adjusted relative risk 100 70 40 10 5 1.0 1.0 Women Men 93.2 42.1 0 <22 <23 23-24- 23.9 24.9 25-26.9 27-28.9 29-30.9 31-32.9 33-34.9 35+ Body mass index (kg/m 2 )

Risk of type 2 diabetes associated with level of physical activity U.S. Nurses Health Study Relative Risk 1 0.8 0.6 0.4 0.2-23% -25% Adjusted for age, smoking. hypertension, family history, menopause, high cholesterol -38% -46% Hu et al., JAMA 282:1433, 1999 0 8 year follow-up Q1 Q2 Q3 Q4 Q5 Quartile of physical activity vs Q1

Regional fat distribution, type 2 diabetes and insulin resistance

Visceral Adipose Tissue VAT= 75.7% Total Fat = 738.53 cm 2 VAT= 20.5% Total Fat = 728.46 cm 2

Association between visceral abdominal fat and Metabolic Syndrome 3.0 * Men 5.0 4.5 * Women OR % (95% CI) 2.5 2.0 1.5 * OR % (95% CI) 4.0 3.5 3.0 2.5 2.0 * * 1.5 1.0 1.0 Normal Weight Overweight Obese Normal Weight Overweight Obese Odds ratio (OR) calculated for 50 cm 2 increment in visceral fat. Goodpaster et al. Archives of Internal Medicine, 165:777-783, 2005.

Type 2 diabetes Aging Insulin Resistance Genetics Obesity/ sedentary life style Other conditions: acromegaly Cushing s disease lipodystrophy anti-insulin receptors Olefsky JM. In: Endocrinology. 2nd ed. 1989:1369-1388. Reaven GM. Clinical Diabetes. 1994;12:32-36. Seely BL, Olefsky JM. In: Insulin Resistance. 1993:187-252.

Insulin Resistance: Definitions Insulin Sensitivity Ability of insulin to lower circulating glucose stimulate glucose utilization: muscle and fat suppress glucose production: liver Insulin Resistance Condition of low insulin sensitivity

Saltiel AR, Olefsky JM. Diabetes. 1996;45:1661-1669. How Does Insulin Resistance Lead to Type 2 Diabetes? Receptor + postreceptor defects Glucose Peripheral Tissues (Muscle) Insulin resistance Liver Increased glucose production Pancreas Impaired insulin secretion

Progression to Type 2 Diabetes Genetics Insulin resistance Hyperinsulinemia Acquired Obesity Sedentary lifestyle Aging Compensated insulin resistance Normal glucose tolerance Genetics Impaired glucose tolerance β-cell "failure" Type 2 diabetes Insulin resistance Hepatic glucose output Insulin secretion Acquired Glucotoxicity FFA levels Other Kruszynska Y, Olefsky JM. J Invest Med. 1996;44:413-428.

Insulin Resistance Obesity and physical inactivity are both related to insulin resistance.

Obesity, Physical Activity and Energy Balance Risk factor for cardiovascular disease, insulin resistance syndrome and type 2 diabetes. Energy balance is a primary factor involved in obesity, weight loss, weight maintenance. Negative energy balance = weight loss Positive energy balance = obesity

Obesity, Physical Activity and Energy Balance Energy expenditure during walking can be predicted by walking speed and body weight. A 120-lb. person walking for 30 min will burn 3.6 Kcal/min, or 108 Kcal in 30 min. A 200-lb. person will burn ~160 Kcal at that speed in 30 min. It requires ~3500 Kcal to burn off a pound of body fat. Therefore, it will take a 120-lb. person 16.2 hours of walking, or 49 miles, to burn a pound of body fat! A 200-lb. person will have to walk only 34 miles!

Learning Activity Use the table below to calculate approximately how many miles you would need to walk in order to burn a pound of body fat. Choose 2 different speeds to see how they compare. Speed (mph) Body weight (lb.) 80 100 120 140 160 180 200 kcal/min 2.0 1.9 2.2 2.6 2.9 3.2 3.5 3.8 2.5 2.3 2.7 3.1 3.5 3.8 4.2 4.5 3.0 2.7 3.1 3.6 4.0 4.4 4.8 5.3 3.5 3.1 3.6 4.2 4.6 5.0 5.4 6.1 4.0 3.5 4.1 4.7 5.2 5.8 6.4 7.0

Obesity, Physical Activity and Energy Balance To put this in perspective, eating an average candy bar (~200 Kcal) only every other day for a month will add one pound of body fat! Negative energy balance = weight loss Positive energy balance = obesity

Exercise for weight loss Exercise is typically not effective by itself to induce substantial weight loss. Exercise, however, may help with long-term weight maintenance. Exercise may also benefit insulin resistance independent of weight loss.

Decreased risk for type 2 diabetes with increased physical activity 1.0 0.9 0.8 0.7 0.6 0.5 Kelley, D.E. and Goodpaster, B.H. Effects of Exercise on Glucose Homeostasis in Type 2 Diabetes Mellitus, MSSE 2001. 0.4 LOW MEDIUM HIGH Physical Activity Level

Exercise Training Intrinsic Muscle Properties Muscle Mass Capillary number Bioenergetics Fiber Type Blood Flow LPL Mitochondria Oxidative enzymes CPT I Insulin signaling pathways GLUT 4 Hexokinase Glycogen synthase Glucose Storage Space Triglyceride Glucose Availability? Glucose Extraction Glucose Utilization Blood Glucose Control

Effect of the volume and intensity of exercise training on insulin sensitivity Houmard et al. J Appl Phys, 2004.

Exercise and Weight Loss Have Additive Effects on Insulin Sensitivity in Obese Subjects at Risk for the Development of Type 2 Diabetes 12.0 10.0 8.0 * * * PRE POST 6.0 4.0 2.0 0.0 EXERCISE DIET EXERCISE + DIET GROUP Goodpaster, Katsiaras and Kelley, Diabetes, 2003.

Effects of exercise on glucose homeostasis in type 2 diabetes Citation Design Subjects Exercise Intensity/ Duration Intervention Duration Glucose control Insulin Sensitivity Insulin Secretion Ronnemaa et al. 1986 RCT: Exercise 25 men and women 5-7x/wk; 70% VO 2 max 45 min 4 months HbA1c 1%; FPG 2hPPG NC Fasting insulin 2h PPI Uusitupa et al. 1996 RCT: Diet +Exercise 86 men and women 3-4x/wk; Aerobic 30-60 12 months HbA1c 0.5%; NC HbA1c in 50%; FPG NC Fasting insulin Leon et al. 1984 RCT: 5 types of Exercise intervention 50 men 2-4x/wk 70% VO 2 max 30-60min 3 months FPG HbA1c 2hPPG 60minEx NC Fasting insulin PPI Krotkiewski et al. 1985 Non- Randomized 24 men and women 3x/wk 80% VO 2 max 50 min 3 months FPG 2hPPG Fasting insulin PPI Bogardus et al. 1984 RCT: Diet+Exercise vs Diet only 18 men and women 3x/wk 75% VO 2 max 30 min 3 months FPG: No additional effect of exercise Ex in Non-ox. IVGT- Exercise vs Diet only Poirier et al. 1996 Non- Randomized 11 men 3x/wk 60% VO 2 max 60 min 6 months FPG HbA1c NC Fasting insulin Reitmann et al. 1984, Non- Randomized 6 men and women 5-6x/wk 75% VO 2 max 20-40 min 1.5-2.5 months FPG PPG HbA1c ND NC HGP Fasting insulin PPI

Changes During Acute Exercise Energy expenditure measured as the amount of oxygen utilization during high intensity exercise can increase 20 X resting levels. Heart rate, blood pressure and cardiac output increase. Both fat and carbohydrate (glucose) can be used as fuel during exercise. Higher intensity = more glucose utilization, lower to medium intensity = more fat utilization.

Exercise Training : Long Term Effects Aids in blood glucose control Increases insulin sensitivity Improves blood lipids Decreases blood pressure Aids in weight reduction Physical work capacity greater Psychological improvements

If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health - Hippocrates (460-377 B.C.)

Recommended Readings 1) Mokdad, A.H., et al., The continuing increase of diabetes in the US. Diabetes Care., 2001. 24(2): p. 412. 2) Ross, R., et al., Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Annals of Internal Medicine, 2000. 133(2): p. 92-103. 3) Goodpaster, B.H., et al., Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes, 1999. 48(4): p. 839-847. 4) Goodpaster BH, et al.: Enhanced Fat Oxidation through Physical Activity is Associated with Improvements in Insulin Sensitivity in Obesity. Diabetes, 52:2191-2197, 2003.