Exercise and Diabetes

1. Exercise and Diabetes

2. “in some people suffering from this affliction, exercise can improve the condition and should be done regularly. In more extreme cases its effects worsen the condition. These people should rest until the condition improves.” -Sushruta in 600 BC.

3. 1921 • Insulin was discovered • Diabetes turned from a fatal disease to a treatable disease • New challenges for clinicians and researchers

4. Why should people with diabetes exercise? • Exercise generally lowers blood glucose resulting in decreased insulin or OHA requirements. • CVD risk factors are potentially improved by regular exercise. • Exercise may prevent or delay the progression of diabetes related complications. • Exercise improves general health.

5. Outline • Regulation of glucose fluxes during exercise • Non-insulin dependent diabetes • Insulin dependent diabetes • Practical information

6. Control of Glucose Fluxes during a Bout of Exercise

7. Sensors Carotid Sinus Liver/Portal Vein Working Muscle Adipose Pancreas Substrates and Signals that Control Glucose Fluxes during Exercise Brain Autonomic Nerve Activity Working Muscle Adrenal Adrenal Intestine Epi ? Glycerol NEFA Amino Acids Lactate Amino Acids IL6 Glucagon Blood Glucose Insulin GNG Gly Liver

8. Glucose homeostasis is usually maintained despite increased glucose uptake by the working muscle Moderate Exercise 1 0 0 8 0 Blood Glucose (mg/dl) 6 0 4 0 2 0 0 5 Rates of Glucose Entry and Removal from the Blood (mg•kg-1•min-1) 4 3 Entry 2 Removal 1 0 - 3 0 0 3 0 6 0 Time (min)

9. Endocrine and Sympathetic Nerve Response to Exercise Exercise 16 120 Glucagon Arterial Arterial 12 80 Glucagon Insulin (pg/ml) (µU/ml) 8 40 Insulin 0 0 Norepinephrine 300 Arterial 200 Catecholamines (pg/ml) 100 Epinephrine 0 -60 -30 0 30 60 90 120 150 Time (min)

10. 7 6 5 Glucagon mg·kg-1·min-1 4 and 3 Insulin 2 1 Epinephrine 0 60 120 Time (minutes) Changes in glucagon and insulin are the main regulators of hepatic glucose production during exercise

11. Moderate Exercise 1 0 0 8 0 Blood Glucose (mg/dl) 6 0 4 0 2 0 0 5 Rates of Glucose Entry and Removal from the Blood (mg•kg-1•min-1) 4 3 Entry 2 Removal 1 0 - 3 0 0 3 0 6 0 Time (min)

12. When glucose removal exceeds glucose entry, hypoglycemia ensues Moderate Exercise 1 0 0 8 0 Blood Glucose (mg/dl) 6 0 4 0 2 0 0 5 Rates of Glucose Entry and Removal from the Blood (mg•kg-1•min-1) 4 3 Entry 2 Removal 1 0 - 3 0 0 3 0 6 0 Time (min)

13. When glucose entry exceeds glucose removal, hyperglycemia ensues Moderate Exercise 1 0 0 8 0 Blood Glucose (mg/dl) 6 0 4 0 2 0 0 5 Rates of Glucose Entry and Removal from the Blood (mg•kg-1•min-1) 4 3 Entry 2 Removal 1 0 - 3 0 0 3 0 6 0 Time (min)

14. Non-insulin dependent diabetes

15. Views on Exercise • Exercise and temperance can preserve something of our early strength even in old age. Cicero (106-43 BC)

16. Views on Exercise • Those who think they have not time to exercise will have to find time for illness. Edward Stanley, Earl of Derby (1826-1893)

17. Views on Exercise • Bodily exercise, when compulsory, does no harm to the body. Plato (428-348 BC)

18. Views on Exercise • Immature faddists are continuously proclaiming the value of exercise; four people out of five are more in need of rest than exercise. Logan Clendening (1884-1945)

19. Views on Exercise • I get my exercise acting as a pallbearer to my friends who exercise. Chauncey Depew (1834-1928)

20. Views on Exercise • To get back my youth I would do anything in the world, except take exercise, get up early or be respectable. Oscar Wilde (1854-1900)

21. Views on Exercise • I have never taken any exercise except sleeping and resting. Mark Twain (1835-1910)

22. Views on Exercise • If it weren't for the fact that the TV set and the refrigerator are so far apart, some of us wouldn't get any exercise at all.  Homer Simpson (1961-2005)

23. Views on Exercise • If by exercise you mean video games, then 2 h a day is about right. Micah Joe Wasserman (1991-present)

24. People need to be Physically Active! • Our genetic makeup has evolved based on a physically active culture of hunting and gathering and periods of feast and famine. • In the absence of the need to hunt and gather and with food always available we need to make an effort to incorporate physical activity in our lives.

25. Genes determine Characteristics of the Body To survive, people in early times had to have genes that permitted the body to store fuel in times of excess so that they would have a source of energy during times of famine.

26. Those genes that permit efficient food storage are termed, “Thrifty Genes”. Thrifty genes cause rapid weight gain in times of abundant food supply. The advantage of this trait is that the bearer is much more likely to survive in the absence of food.

27. “obesity is an unintentional consequence of societal progress” Dr. Phil

28. The Problem with Thrifty Genes…. The problem is that in a society where food is always plentiful and physical activity is not a part of the lifestyle, thrifty genes cause obesity, diabetes and related problems.

29. Because of the human genome it is necessary to re-introduce physical activity into our lives.

30. Exercise Greases the Wheels Extracellular Intracellular glucose 6-phosphate glucose • hexokinase # • hexokinase compartmentation • spatial barriers • blood flow • capillary recruitment • spatial barriers Membrane • transporter # • transporter activity

31. Glucose Metabolism Non-oxidative 6 Oxidative Glucose Disposal 4 during a 40 mU/m2·min Insulin Clamp 2 (mg/kg-FFM·min) 0 Before After Exercise Program (12 wks) Regular exercise increases insulin-stimulated glucose disposal in people with non-insulin-dependent diabetes

32. 12 Muscle 8 GLUT4 Protein (OD units/1000) 4 0 Before After Exercise Program (12 wks) Regular exercise increases skeletal muscle GLUT4 content.

33. Regular exercise reduces fasting blood glucose in people with non-insulin-dependent diabetes. 150 Fasting 100 Blood Glucose Concentration (mg/dl) 50 0 Before After Exercise Program (6-10 wks)

34. CVD risk factors are potentially improved by regular exercise • Glucose Intolerance • Hyperinsulinemia • Hyperlipidemia • Coagulation Abnormalities • Hypertension • Obesity

35. Insulin-dependent diabetes

36. Exercise-induced hypoglycemia • While exercise-induced hypoglycemia is generally not common in non-insulin dependent diabetes, it is extremely prevalent in insulin dependent diabetes. • Hypoglycemia may occur during exercise or after exercise (even up to 24 h following the cessation of an exercise session). • Hypoglycemia can be prevented by eating more, taking less insulin, or both.

37. Endocrine and Sympathetic Nerve Response to Exercise Exercise 16 120 Glucagon Arterial Arterial 12 80 Glucagon Insulin (pg/ml) (µU/ml) 8 40 Insulin 0 0 Norepinephrine 300 Arterial 200 Catecholamines (pg/ml) 100 Epinephrine 0 -60 -30 0 30 60 90 120 150 Time (min)

38. Insulin Profiles 0 4 8 12 16 20 24 Humalog, Novolog Rapid Short Regular Intermediate NPH Intermediate Lente Ultralente, Lantus Long

39. Moderate exercise Lower lunch & dinner Humalog Hypoglycemia! Moderate exercise Insulin adjustment scenarios 0 4 8 12 16 20 24 Lantus (at bedtime) + Humalog (with meals) Hypoglycemia!!

40. 0 4 8 12 16 20 24 Marathon training Lower or even eliminate breakfast & lunch Humalog Hypoglycemia!! Marathon training Insulin adjustment scenarios Lente (at bedtime) + Humalog (with meals) Hypoglycemia!!

41. Exercise accelerates absorption of insulin from subcutaneous depot Exercise or Continued Rest 45 Exercise SubQ Insulin 30 Arterial Insulin (mU/ml) 15 Rest 0 -30 0 30 60 Time (minutes)

42. Insulin-stimulated glucose utilization is increased during exercise 18 Exercise 12 Glucose Utilization (mg/kg·min) Rest 6 0 100 1 10 1000 Insulin (µU/ml)

43. Proposed mechanisms by which acute exercise enhances insulin sensitivity • Increased muscle blood flow • Increased capillary surface area • Direct effect on working muscles • Indirect effect mediated by insulin-induced suppression of FFA levels

44. Glucose tolerance is improved, and the body is more insulin sensitive for an extended period after exercise. 90 min of Moderate Exercise 60 Area Under the Blood 40 Glucose Curve during an OGTT ( mg/dl min) • 10 0 2 day 4 day 6 h 12 h 1 day Pre- Exercise Post-Exercise

45. Blood glucose increases during exercise in people with poorly-controlled diabetes Moderate Exercise 3 0 0 28 0 Blood Glucose (mg/dl) 26 0 24 0 22 0 200 5 Rates of Glucose Entry and Removal from the Blood (mg•kg-1•min-1) 4 3 Entry 2 Removal 1 0 - 3 0 0 3 0 6 0 Time (min)

46. 300 200 100 0 Exercise-induced increase in portal vein glucagon is exaggerated by poorly-controlled diabetes Non-Diabetic Diabetic Moderate Exercise Moderate Exercise 300 Arterial Portal Vein Arterial 200 Hepatic Vein Immunoreactive Glucagon (pg/ml) 100 0 -50 0 50 100 150 -50 0 50 100 150 Time (min) Time (min)

47. Sympathetic drive to the liver is increased during exercise in diabetes Moderate Exercise Non-Diabetic 12 Diabetic Hepatic Norepinephrine Spillover (ng·kg-1·min-1) 8 4 0 -50 0 50 100 150 Time (min)

48. Practical Information

49. Factors that influence the response to acute exercise in the general population (including those with diabetes) •Exercise intensity, duration, and type • Fitness level • Nutritional state • Temporal relationship to meal • Calories and content of meal • Environmental factors

50. General Considerations in People with Diabetes • Physical screening prior to starting an exercise program • Metabolic control • Blood glucose monitoring • Food intake • Insulin administration (when applicable) • Make physical activity compatible with a person's lifestyle and interests