COMPLIMENTARY CE Fundamentals of Exercise Physiology and T1D Jointly Provided by Developed in collaboration with 1 INTRODUCTION TO PHYSICAL ACTIVITY AND T1D 2
Many People with T1D Have Lower Levels of Physical Activity Study Study Type % Study Defined Low Levels of Physical Activity DCCT Retrospective analysis 19% EURODIAB Prospective cohort study 36% FINNDIANE Cross sectional 44% DPV Database Cross sectional 63% Makura CB, et al. BMC Endocr Disord. 2013;13:37; Tielemans SM, et al. Diabetologia. 2013;56:82 91; Waden J, et al. Diabetologia. 2015;58:929 36; Bohn B, et al. Diab Care. 2015;38:1536 43. 3 ADA Aerobic Exercise Recommendations Adults: 150 minutes/week of moderate to vigorous physical activity (brisk walking or greater), with no more than 2 days off in a row plus strength training 2 3 x/week on nonconsecutive days. For younger and more physically fit individuals, shorter durations (75 min/week) of vigorousintensity or interval training may be sufficient. Youth: 60 minutes/day of moderate to vigorous physical activity (420 min/week), including vigorous intensity activities 3 or more days/week and strength building activities (for muscle and bone) 3 or more days/week. ADA. Diabetes Care. 2018;41(Suppl 1):S38 50. 4
Benefits of Exercise in Diabetes Weight management, increased lean body mass Reduced cardiovascular risk factors Lower blood pressure Lower unfavorable and higher favorable lipids Improved HbA1c and insulin sensitivity Reductions in microvascular complications Retinopathy Microalbuminuria Psychological benefits Improved sense of well being Improved self esteem ADA. Diabetes Care. 2018;41(Suppl 1):S38 50; Bohn B, et al. Diab Care. 2015;38:1536 43. 5 Attitudes and Barriers to Exercise Among People with T1D Are Multifactoral Health and medical How blood glucose could be affected by activity Hypoglycemia Complications due to diabetes Other non diabetes related health problems Time, work, and lifestyle Demands on their time is greater barrier than diabetes for most people Lascar: PLoS One. 2014; 9(9): e108019. Demands in the home or caring for children or relatives Erratic lifestyle a perceived lack of time Social and personal Lack of motivation to exercise Embarrassment or fear of failure Body image concerns Environmental Access/cost of sports facilities Weather Lascar N, et al. PLoS One. 2014;9:e108019. 6
Factors that Contribute to Increased Hypoglycemia During Exercise in T1D Absence of physiologic decrease in insulin secretion Increase in absorption of insulin from subcutaneous tissue Increase in rate of glucose transport into muscle Blunting of counter regulatory hormone responses (especially with sleep) Diminished hepatic glucose production Riddell M, et al. Lancet Diab Metab. 2017;5:377 90. 7 KEY POINT #1 DIFFERENT FORMS OF EXERCISE HAVE DIFFERENT PHYSIOLOGIC EFFECTS 8
Blood Glucose Effects of Different Types of Exercise Aerobic Mixed Anaerobic Workrate Glucose trends Main variables Intensity and duration of exercise, insulin to glucagon ratio, fitness, nutrition, initial glucose concentration Intensity and duration of exercise, insulin to glucagon ratio, counter regulatory hormones, lactate concentration, fitness, nutrition, initial glucose concentration Intensity and number of intervals, insulin concentration, counter regulatory hormones, lactate concentration, fitness, nutrition, initial glucose concentration Riddell M, et al. Lancet Diab Endo. 2017;5:377 90. 9 Intense Exercise Can Cause Hyperglycemia and May Increase Needs During Recovery Glucose is exclusive fuel used during intense exercise (>80% VO 2 max) Regulation of glucose production and utilization are different at higher versus lower exercise intensities release is able to control glucose rise in controls Without insulin administration, glucose rise is unchecked in T1D Blood Glucose Level Blood Glucose Level (mg/dl) (mmol/l) 126 106 90 72 7 6 5 4 (mg/dl) (mmol/l) 126 106 90 72 Controls 10 sec sprint 40 20 0 20 40 60 80 100 120 Time (min) 7 6 5 4 T1D 10 sec sprint 40 20 0 20 40 60 80 100 120 Time (min) Marliss EB, et al. Diabetes. 2002;51 Suppl 1:S271 83; Fahey AJ, et al. J Clin Endocrinol Metab. 2012;97:4193 200. 10
Resistance Exercise Presents an Opportunity for Protection Against Hypoglycemia Individuals who develop exerciseassociated hypoglycemia may benefit by adding resistance training before aerobic activity Attenuates declines in glucose May lower reliance on glucose supplementation Individuals with exercise associated hyperglycemia may benefit from adding aerobic exercise before resistance training Glucose Glucose (mmol/l) (mg/dl) 2 36 1 0 1 2 3 4 5 90 30 15 0 15 30 45 Time (min) Yardley JE, et al. Diabetes Care. 2012;35:669 75. Significant difference from baseline (P <.05) *Significant difference from resistance exercise (P <.05) 11 18 0 18 36 54 72 * * * Resistance exercise Aerobic exercise KEY POINT #2 PHYSIOLOGIC MECHANISMS MAINTAIN TIGHT GLUCOSE LEVELS DURING EXERCISE IN THE ABSENCE OF DIABETES 12
Physiologic Mechanisms Maintain Tight Glucose Levels During Exercise ADRENALS catecholamines (epinephrine, norepinephrine) insulin glucagon PANCREAS MUSCLE LIVER Glucose (~90 mg/dl) Liver Glycogen (70 80 g) Muscle Glycogen (350 800 g) 13 KEY POINT #3 EXERCISE IN T1D LEADS TO GLUCOSE IMBALANCE DUE TO ALTERED PHYSIOLOGIC RESPONSES 14
Exercise in T1D Can Lead to Hypo or Hyperglycemia Because of Impaired Physiologic Response Euglycemia insulin counter regulation (glucagon, growth hormone, cortisol, catecholamines) Hypoglycemia Relative hyperinsulinemia Impaired counter regulation Hyperglycemia Relative hypoinsulinemia counter regulation (catecholamines, etc) Anaerobic metabolism (lactate production) A B C Counter regulatory hormones or or Counter regulatory hormones or Counter regulatory hormones Chu L, et al. Phys Sportsmed. 2011;39:64 77. 15 Aerobic Exercise Without Adjusting Promotes a Variable Drop in Glucose and May Cause Hypoglycemia (mmol/l) (mg/dl) 0 0 Change in Glucose 1.39 2.78 4.16 5.55 25 50 75 100 Exercise Baseline 15 min min 35 min 55 Exercise time T1D, no insulin adjustment Δ=~ 63 mg/dl 43% become hypoglycemic 75 min Recovery 105 min T1D, age 8 17 years, n=49 75 min of intermittent aerobic exercise at ~60% VO 2 max The Diabetes Research in Children Network (DirecNet) Study Group, et al. Diabetes Care. 2006;29:2200 4. 16
Symptoms of Hypoglycemia May Be Blunted in T1D (mmol/l) (mg/dl) 4.0 72 Glucose 3.0 54 Individuals without diabetes Release of hormones Warning symptoms Cognitive impairment Individuals with T1D and hypoglycemia unawareness Deficient glucagon and poor catecholamine response, reduced symptoms 2.0 36 Martin Timon I, et al. World J Diabetes. 2015;6:912 26. 17 KEY POINT #4 GLUCOSE UPTAKE IS HIGH DUE TO BOTH INSULIN ACTION AND MUSCLE CONTRACTION 18
Both Available and Muscle Contraction Increase Glucose Uptake into Skeletal Muscle via Distinct Mechanisms glucose glucose Receptor Receptor GLUT 4 vesicles GLUT 4 vesicles Muscle cell Muscle cell Rest Muscle Contraction 19 Both Available and Muscle Contraction Increase Glucose Uptake into Skeletal Muscle via Distinct Mechanisms Receptor glucose Receptor HYPOGLYCEMIA Receptor glucose GLUT 4 vesicles Muscle cell Rest GLUT 4 vesicles Muscle cell Hyperinsulinemia/ muscle contraction, increased blood flow Muscle cell GLUT 4 vesicles Muscle contraction, increased blood flow 20
KEY POINT #5 EXERCISE HAS BOTH IMMEDIATE AND DELAYED EFFECTS ON BLOOD GLUCOSE 21 Post Exercise Glucose Uptake Remains Elevated for Hours to Replenish Muscle Glycogen Stores Glucose uptake Early hypoglycemia risk Late hypoglycemia risk Starting approximately 7 11 hours after exercise, lasting ~6 hours Rest Moderateintensity exercise in afternoon 1600 1800 2000 2200 2400 0200 0400 Time Adapted from McMahon SK, et al. J Clin Endocrinol Metabol. 2007;92:963 8. 22
KEY POINT #6 THE BODY ADJUSTS ITS SOURCE OF ENERGY AS INTENSITY OF EXERCISE AND OVERALL FITNESS CHANGE 23 Fuel Utilization: Muscle Glycogen Demand Increases with Intensity Lower intensity exercise High lipid (fat) use Higher intensity exercise High muscle glycogen use High plasma glucose use cal kg 1 min 1 300 250 200 150 100 50 Lipids Muscle glycogen Plasma glucose 0 Low intensity Moderate intensity High intensity Romijn JA, et la. Am J Physiol. 1993;265:E380 91; van loon LJ, et al. J Physiol. 2001;536:295 304. 24
KEY POINT #7 INSULIN SENSITIVITY INCREASES WITH FITNESS 25 Training Increases Sensitivity and May Lower Exogenous Requirements Untrained/overweight Trained/normal weight 0 08:00 12:00 16:00 20:00 24:00 04:00 Clock Time (hours) Schematic; derived from expert opinion. 26
KEY POINT #8 COOLDOWN MINIMIZES INCREASE IN GLUCOSE LEVELS DUE TO MULTIPLE MECHANISMS 27 Cool Down Can Attenuate Hyperglycemia Risk After Vigorous Exercise Counter regulatory hormones and high lactate levels may increase blood glucose levels in early recovery Hyperglycemia in early recovery can be attenuated by a prolonged passive cool down at a moderate intensity (30 50% VO 2 max) Monitoring of glucose is essential Modified from Exercise Physiology Energy, Nutrition, & Human Performance, 6e. Editors: William D. McArdle, Frank I. Katch, Victor L. Katch. 28
KEY POINT #9 SHORT TERM RISK OF HYPOGLYCEMIA DURING EXERCISE IS INCREASED BY RECENT HYPOGLYCEMIA AND RECENT EXERCISE 29 Exercise Can Increase Hypoglycemia Due to Multiple Mechanisms Glucose (mmol/l) 216 180 144 Glucose (mg/dl) 12 10 8 45 min cycling Person with Diabetes Repeated occurrence of post exercise hypoglycemia can lead to reduced counter regulation, which in turn may increase risk of hypoglycemia and hypoglycemic unawareness 108 6 72 4 36 2 0 0 9:00 15:00 21:00 3:00 9:00 Time of Day (24:00h) Iscoe KE, et al. Diabetes Technol Ther. 2006;8:627 35. 30
Vicious Cycle of Hypoglycemia and Exercise Exercise Blunted counter regulatory responses Blunted counter regulatory responses Hypoglycemia Ertl AC, Davis SN. Diabetes Metab Res Rev. 2004;20(2):124 30. 31 Summary 1. Different forms of exercise have different effects 2. Physiologic mechanisms maintain tight glucose levels during exercise in the absence of diabetes 3. Exercise in T1D leads to glucose imbalance due to altered physiologic responses 4. Glucose uptake is high due to both insulin action and muscle contraction 5. Exercise has both immediate and delayed effects on blood glucose 6. The body adjusts its source of energy as intensity of exercise and overall fitness change 7. sensitivity increases with fitness 8. Cooldown minimizes increase in glucose levels due to multiple mechanisms 9. Short term risk of hypoglycemia during exercise is increased by recent hypoglycemia and recent exercise 32