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Exercise and Endocrine Care

Exercise and Endocrine Care. Eric Sherman MAJ, USAF, MC Pediatric Endocrine Fellow. Objectives. Discuss the maintenance of euglycemia Review some basics of exercise physiology Review exercise physiology in type 1 diabetes Review the literature on exercising safely with type 1 diabetes

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Exercise and Endocrine Care

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  1. Exercise and Endocrine Care Eric Sherman MAJ, USAF, MC Pediatric Endocrine Fellow

  2. Objectives • Discuss the maintenance of euglycemia • Review some basics of exercise physiology • Review exercise physiology in type 1 diabetes • Review the literature on exercising safely with type 1 diabetes • Review other endocrine disorders and any exercise recommendations

  3. Fasting state • Reduced insulin secretion • Increased levels of cortisol, GH, glucagon and epinephrine • Glucose production enhanced • Mobilization of fatty acids for energy Sperling Pediatric Endocrinology

  4. Fed state • Increased insulin secretion (w/in 20-30 min) and decreased glucagon secretion • Glycogen synthesis enhanced • Enhanced glucose uptake in muscle • Suppression of gluconeogenesis • Lipid synthesis activated and lipolysis suppressed Sperling Pediatric Endocrinology

  5. Pierce Br. J. Sports Med (1999)

  6. Exercise physiology Decline in serum glucose Increased counter- regulatory hormones Increased glucagon secretion Decreased plasma insulin secretion Muscular glucose production + Fatty acids mobilized from adipose tissue + Gluconeogenesis from lactate (liver) + GLUT4 stimulated transport of glucose into muscle Euglycemia maintained

  7. After exercise • Similar to fasting state • Goal to rebuild skeletal muscle glycogen stores • Increased GLUT4 transport (insulin not initially required) • Full replenishment of muscle stores requires insulin Pierce Br. J. Sports Med (1999)

  8. Counter regulatory hormones • Glucagon (alpha cells in pancreas) • Most efficient stimulator of gluconeogenesis • Requires liver glycogen stores to acutely increase BG • Growth hormone (anterior pituitary) • Impaired glucose uptake • Promotes lipolysis • Increased hepatic glucose production Sperling Pediatric Endocrinology

  9. Counter regulatory hormones • Cortisol (adrenal cortex) • Enhances gluconeogenesis • Epinephrine (adrenal medulla) • More potent than norepi • Inhibit insulin secretion • Increase glucose secretion from liver and lactate from muscle • Norepinephrine (same as epi) Sperling Pediatric Endocrinology

  10. Quick Primer on Type 1 Diabetes • Incidence = ~20/100,000/year in US and ↑ • Immune destruction of pancreatic beta cells • Up to 40% of patients present after age 18 • Treatment = insulin • Prevention trials have all failed

  11. Types of insulin • Short acting • Regular • Aspart (Novolog) – primary insulin in pumps • Lispro (Humalog) • Intermediate acting • NPH • Long acting • Detemir • Glargine (Lantus)

  12. Insulin regimens • Traditional • NPH + regular (now Novolog/Humalog) in AM • Novolog at dinner • NPH at bedtime • Basal-bolus • Lantus once daily + Novolog at meals • CSII (insulin pump) Intensive treatment

  13. Diabetes and exercise • Exercise may decrease risk of diabetes complications • Hypoglycemia • Increased risk of DKA • Unmasking CAD

  14. What is different in diabetes • Constant non-physiologic insulin supply • Variable insulin absorption • Suboptimal release of counter-regulatory hormones (especially during sleep) • Increased skeletal muscle uptake following exercise • Increased insulin sensitivity after exercise McMahon JCEM (2007)

  15. Exercise physiology in diabetes Decline in serum glucose Increased counter- regulatory hormones Increased glucagon secretion Decreased plasma insulin secretion Muscular glucose production + Fatty acids mobilized from adipose tissue + Gluconeogenesis from lactate (liver) + ↑GLUT4 stimulated transport of glucose into muscle Hypoglycemia

  16. Hypoglycemia • Older data suggests that risk of hypoglycemia lasts up to 31 hours after exercise Macdonald Diabetes Care (2007) • 2-4% of deaths in type 1 diabetes attributed to hypoglycemia Cryer Diabetes Care (2003) • 2 episodes per week of severe hypoglycemia in well controlled diabetics Cryer Diabetes Care (2003) • One episode of hypoglycemia blunts responses to subsequent hypoglycemia for several daysHopkins Diab Res Clin Prac (2004)

  17. And now for some real data…

  18. Biphasic Hypoglycemia • 9 Australian adolescents exercised at ~ 55% VO2 peak (compared with 45 minutes of rest) – moderate intensity • Euglycemic clamp with constant insulin infusion and glucose adjusted to keep BG between 90-108 • Primary endpoint: hypoglycemia as measured by increased GIR McMahon JCEM (2007)

  19. McMahon JCEM (2007)

  20. McMahon JCEM (2007) • Early hypoglycemia • Lack of physiologic decrease in insulin secretion • Late hypoglycemia (MN – 4AM) • Imbalance between glucose production and use • Need to replete glycogen stores • Blunted counter-regulatory responses during sleep

  21. McMahon JCEM (2007) • Lack of hypoglycemia from 5P – MN • Elevated counter-regulatory hormones may have increased fatty acid oxidation Growth Hormone Fatty Acids Cortisol

  22. DirecNet • A multi-center trial that studied the impact of exercise under a variety of conditions on 50 children with type 1 diabetes • 75 minute exercise session at 4PM (55% VO2 max) • 11/50 hypoglycemic (23%) – BG < 60 • 26/50 had BG < 70 at some point • Sharp rise in GH, but no change in cortisol or glucagon secretion Diabetes Care (2006)

  23. DirecNet • Initial BG < 120 • 86% hypoglycemic, 100% BG < 70 • Initial BG 120-180 • 13% hypoglycemic, 44% BG < 70 • Initial BG > 180 • 6% hypoglycemic, 28% BG < 70 Diabetes Care (2006)

  24. Conclusions • Glucose production ≠ glucose utilization • Counter regulatory hormones not doing their job, even in presence of hypoglycemia Diabetes Care (2006)

  25. DirecNet • 10P – 6A - mean BG 131 on exercise days and 154 on sedentary days • Twice as many hypoglycemic events between 10P – 6A on days with exercise compared to sedentary days • J Peds (2005)

  26. How many carbs before exercise? • 9 adult subjects on NPH and Novolog exercised for 60 minutes (50% VO2 max) with euglycemic clamp – 3 hours post breakfast • Given 0, 15 & 30 g of carbs prior to exercise • Based on GIR and amount of pre-exercise carbs, a regression equation calculated • 35 g of carbs prevents acute hypoglycemia • 40 g of carbs prevents acute and late hypoglycemia • Dube Med & Sci in Sports & Exercise (2005)

  27. Reduction in pre-meal insulin • 8 adult males in randomized crossover trial • Exercised at 25, 50 & 75% of VO2 max for 30 and 60 minutes (90 minutes after eating) • Injected 25, 50 & 100% of typical Humalog dose • 100% of Humalog dose associated with significantly reduced BG compared with dose reduction (all groups) Rabasa –Lhoret Diabetes Care (2001)

  28. Insulin pumps • Is suspending them an option? • 50 patients aged 8-17 in random crossover trial (on and off pump during 75 minutes of exercise at 55% VO2 max) DirecNet Diabetes Care (2006)

  29. DirecNet Diabetes Care (2006) • Hypoglycemia 3 times more • common in basal continued • group • Hyperglycemia 4.5 times • more common in basal stopped • group

  30. Another pump study • 10 patients exercised for 45 minutes (60% VO2 max) with pump on and pump off • Wore CGMS for 24 hours after exercise • No difference in hypoglycemic events during exercise (2 in each group) • All 10 had 1-3 hypoglycemic events (BG 50-70) from 2.5 to 12 hours after exercise Admon Pediatrics (2005)

  31. Higher intensity exercise • 7 adults • 30 minutes of moderate exercise (40% VO2 max) • 30 minutes of intermittent high intensity exercise (40% VO2 max + 4s sprints every 2 minutes) • IHE felt to mimic typical toddler activity and adolescent sports Guelfi Diabetes Care (2005)

  32. Guelfi Diabetes Care (2005)

  33. Guelfi Diabetes Care (2005)

  34. Why the difference? • Lactate • Inhibit glucose uptake within skeletal muscle • Stimulate hepatic gluconeogenesis • Catecholamines • Inhibit insulin mediated glucose uptake • Stimulate hepatic gluconeogenesis • GH • Inhibit insulin mediated glucose uptake Guelfi Diabetes Care (2005)

  35. A novel approach • 7 adult males with type 1 diabetes in random crossover trial • Exercised for 20 minutes at 40% VO2 max +/- a 10 s sprint at completion of exercise • Theorized that a short sprint would prevent hypoglycemia • Increase in lactate & catecholamines Bussau Diabetes Care (2006)

  36. Bussau Diabetes Care (2006)

  37. Lactate Fatty acids Epinephrine Norepinephrine Growth hormone Cortisol Glucagon Insulin Bussau Diabetes Care (2006)

  38. ADA and hypoglycemia • Avoid exercise if BG < 100 • Have carbohydrates available during exercise ADA Position Statement Diabetes Care (2004)

  39. My recommendations • Avoid exercise if BG < 100 or > 300 • Check ketones if BG > 250 and exercising • Take 15 g of carbohydrates for every 30 minutes of exercise • Check BG every 30-60 minutes during exercise and as needed • Avoid using legs for injections p/t running (increased absorption) – abdomen better

  40. My recommendations • Check BG after exercise • Disconnect pump during moderate to high intensity exercise, most sporting events and swimming • Check BG prior to bedtime and eat snack with both carbohydrates and protein • Check BG at 2A on intense exercise days

  41. Insulin adjustment • No ADA recommendations • No consensus statements • Depends on timing & spontaneity of exercise • Data suggests a 50% reduction in pre-meal insulin for planned exercise • 25% decrease in evening Glargine if morning exercise planned Pierce Br. J. Sports Med (1999)

  42. Insulin adjustment • Post exercise • Consider decrease in insulin dose of 25-50% • Elite athletes • 50-75% reduction in total daily insulin dose • Hypoglycemia can occur up to 24-36 hours after competition (restoring muscle glycogen) Pierce Br J Sports Med (1999)

  43. Exercise & Hyperglycemia • Physiology • Insulin deficiency • Hepatic glucose production continues without glucose utilization (exaggerated hyperglycemia) • Increased lipolysis leads to FA and ketone production (exaggerated ketosis) Zinker Clinics in Sports Med (1999)

  44. ADA and hyperglycemia • Avoid exercise if BG > 250 and ketones present • Use caution if BG > 300 and no ketones are present ADA Position Statement Diabetes Care (2004)

  45. Preparticipation evaluation • Vital signs • Complete PE including monofilament evaluation • A1C • Yearly eye exam • Microalbumin • Fasting lipid panel • TFTs • Consider formal cardiac stress test

  46. Exercise & cardiovascular dz • Stress test if • Age > 35 • Age > 25 and • Type 2 diabetes for 10 years • Type 1 diabetes for 15 years • Other CAD risk factors • Retinopathy or nephropathy • PVD • Peripheral neuropathy ADA Position Statement Diabetes Care (2004)

  47. Exercise & Retinopathy ADA Position Statement Diabetes Care (2004)

  48. Exercise and Nephropathy • No specific recommendations • ADA says high intensity/strenuous exercise should be avoided unless BP monitoring available • Treatment may limit exercise capacity ADA Position Statement Diabetes Care (2004)

  49. Exercise and peripheral neuropathy • Loss of sensation in feet increases risk of ulcers • Contraindicated • Allowed • Treadmill – Swimming • Prolonged walking – Biking • Jogging – Rowing • Stairmaster – Chair/arm exercises ADA Position Statement Diabetes Care (2004)

  50. Exercise & autonomic dysfunction • Difficult to diagnose • Resting HR > 100 • Orthostasis • Delayed gastric emptying • Cardiac stress test

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