Exercise Prescription for Diabetes PDF

Module 3: Cardiovascular Exercise Principles Week 3 Dr. Tanya Holloway, PhD, ACSM-RCEP Exercise Prescription for Common Chronic Conditions Diabetes Learning Objectives 1. Define diabetes 2. Identify the main physiological processes involved with regulating blood glucose and explain factors co...

Module 3: Cardiovascular Exercise Principles Week 3 Dr. Tanya Holloway, PhD, ACSM-RCEP Exercise Prescription for Common Chronic Conditions Diabetes Learning Objectives 1. Define diabetes 2. Identify the main physiological processes involved with regulating blood glucose and explain factors contributing to high blood glucose levels in type2 diabetics 3. Identify the treatment goal for diabetes and justify the role that exercise has in acute and chronic management 4. Describe the complications that can arise with exercise in diabetics 5. Design effective exercise strategies for management of type 2 diabetes Diabetes A chronic metabolic disease characterized by hyperglycemia as a result of defects in insulin secretion and/or an inability to utilize insulin. Types: Type 1: autoimmune disease that occurs in children and adults caused by destruction of beta cells in the pancreas which stops production of insulin Type 2: metabolic disease caused by insulin resistance in peripheral tissue and defective insulin secretion Gestational Diabetes: glucose intolerance with onset or first recognition during pregnancy due to contra-insulin effects of pregnancy Blood Glucose Control is impaired in Type 2 Diabetes 24 hour Blood Glucose Control Van Dijk et al. Diabetes Journal 2015; 28:24-30 Overview of Glucose Transport in Skeletal Muscle Glucose Blood Ins Ins Exercise Cytosol GLUT-4 vesicle Overview of Glucose Transport Glucose Blood Ins Ins Exercise Cytosol GLUT-4 vesicle KEY POINT: Glucose transport into skeletal muscle can be insulin stimulated OR exercise stimulated Prevalence and Diagnosis scope Prevalence Prevalence of diagnosed diabetes among individuals aged one year and older, by age group and sex, Canada, 2014/15 Diabetes worldwide: We’re number 3! Figure 1-8. Prevalence† of diabetes among individuals aged 20 to 79 years, Europe, North America and Oceania, 2010 Source: Public Health Agency of Canada (2011); adapted from Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diab Res Clin Pract 2010;87:4-14. Diagnostic Criteria Type 2 Diabetes: Progressive Development Type 2 diabetes care: The role of insulin-sensitizing agents and practical implications for cardiovascular disease prevention. Am J Med, 105(1A):20S-26S, 1998. Insulin Stimulated Glucose Transport Insulin Stimulated Glucose Transport Elevated circulating glucose stimulates the release of insulin from the pancreas Insulin acts by binding to its’ receptor on the membrane of target tissues Skeletal muscle: 50-80% of insulin stimulated glucose uptake 40% of body mass Insulin Stimulated Glucose Transport Glucose Blood Ins P IRS P Cytosol P AKT P AS160 GLUT-4 vesicle P KEY POINT: Insulin stimulates the movement of GLUT-4 to the skeletal muscle membrane to enhance glucose transport Pathophysiology of Insulin Resistance Pathophysiology of Insulin Resistance Adipose tissue (AT) becomes insulin resistant before skeletal muscle Insulin Resistant AT Healthy AT Adipocyte hypertrophy inflammation ROS emission lipolysis Caloric surplus FFA-Alb Resulting in the increased release of fatty acids from adipose tissue and the accumulation of in skeletal muscle Frangos SM et al. Biochem J 2021 The Effect of Excess Lipids on Insulin Signaling Adipose issue insulin resistance results in an increase in circulating lipids Lipid transporters begin to accumulate on the skeletal muscle membrane Resulting in the increased transport of lipids into skeletal muscle Excess lipids in skeletal muscle results in the production of reactive lipids: Diacylglycerols (DAGs) Ceramides The accumulation of reactive lipids impair insulin signaling The Effect of Excess Lipids on Insulin Signaling Lipids Hyperglycemia Ins Blood FAT/CD36 FAT/CD36 IRS FFA 1 PKC AKT DAGs Cytosol PP2 DAGs Ceramides 2 Ceramides PKC P AS160 TAGs KEY POINT: High lipid environment results in insulin resistance and hyperglycemia GLUT-4 vessicle Diabetic Complications Hyperglycemia Acute Complications Hyperglycemia Manifestations: Hypoglycemia Potential Causes Diabetes out of control Diabetic ketoacidosis (hyperglycemia, ketosis and metabolic acidosis) Hyperglycemic hyperosmolar nonketotic syndrome Common Symptoms headache weakness fatigue Too much insulin or selected anti-diabetic oral agents Too little carbohydrate Missed meals Excessive or poorly planned exercise Common symptoms: Shakiness Weakness Sweating Anxiety Hunger Chronic Complications Peripheral neuropathies Somatic neuropathy Autonomic neuropathy Nephropathies Retinopathies Macro/microvascular complications Diabetic foot ulcers Infections Peripheral Neuropathy (Somatic) Definition: Symptoms: Cause: Treatment: Peripheral Neuropathy (Autonomic) Definition: Symptoms: Cause: Treatment: Diabetic Retinopathy Definition: Symptoms: Cause: Treatment: Diabetic Nephropathy Definition: Symptoms: Cause: Treatment: Follow the ABCDEs: A – A1C – Most people should aim for an A1C of 7%* or less by managing blood sugars well. A1C is a blood test that is a measure of your average blood sugar level over the past 120 days. B – Blood pressure – Control your blood pressure to less than 130/80* mmHg. C – Cholesterol – The LDL (bad) cholesterol target is less than 2.0* mmol/L. Patient Education to D – Drugs to protect your heart – Speak with your health-care team about Reduce Risk of DM medications. E – Exercise & Eating – Regular physical activity, healthy eating, and Complications maintain a healthy body weight. S – Screening for complications – Ask your health-care team about tests for your heart, feet, kidneys, and eyes. S– Smoking cessation – Stop smoking and seek support for help with quitting. S – Self management, stress, and other barriers – Set goals for yourself to reach the targets and live well with diabetes, such as managing stress effectively. Common Medications Common Medications see Appendix A in ACSM Guidelines Oral anti-hyperglycemics Metformin Rosiglitazone (Avandia) Sulfonylurea (enhance insulin secretion) Glyburide, glipizide Insulin – can be rapid-, intermediate- a combination, or long-acting Humalog Humulin R or N Novolin R or N Treatment Goals For Diabetes 1. Diet – when and what to eat 2. Medication – insulin, oral glucose lowering agents (metformin), antihypertensives, lipid-lowering agents 3. Regular Exercise KEY POINT: Hyperglycemia was present in 13 out of 24hrs in “well controlled” diabetics Type II Diabetic Non-diabetic  150 min or more of moderate-to-vigorous intensity activity weekly, spread over at least 3 days/week, with no more than 2 consecutive days without activity. Shorter durations (minimum 75 min/week) of vigorous-intensity or interval training may be sufficient for younger and more physically fit individuals. Moderate Intensity Continuous Training (MICT) High Intensity Interval Training (HIIT) Exercise Stimulated Glucose Transport Blood Glucose Regulation During Exercise Reciprocal relationship ensures maintenance of plasma glucose when muscle is using pl glucose at a high rate!! Why does insulin decrease with exercise?? What would happen if it did not decrease? Exercise Stimulated Glucose Transport Glucose Ins P IRS LIPIDS P Exercise P AKT P AS160 GLUT-4 vessicle AMPK ADP CaMK Ca2+ ROS KEY POINT: Exercise stimulates the transport of glucose independent of insulin resistance Exercise Stimulated Glucose Transport The stimulation of muscle contraction results in the accumulation of the following: Ca2+ Adenosine diphosphate (ADP) Reactive oxygen species (ROS) The metabolic environment stimulates a signaling cascade by which GLUT-4 moves from inside the cell to the plasma membrane This facilitates the increased uptake of glucose during exercise by the skeletal muscle Research Article Presentations Key evidence leading to the consensus that IMTG may not be directly involved in impairing insulin sensitivity is the finding that individuals who exercise regularly are acutely insulin sensitive despite having high IMTG concentrations (6, 9), commonly referred to as the “athlete’s paradox” (6). Importantly, only 1 session of exercise markedly improves insulin sensitivity (21, 22), and this improvement also occurs in obesity (23). One session of exercise also increases IMTG synthesis and storage, particularly when fat availability is high (7–9). Therefore, by preferentially repartitioning fatty acids that have entered the muscle cell toward storage as IMTG, a single session of exercise may reduce the partitioning of fatty acids toward more metabolically “unfavorable” routes (i.e., excessive formation and accumulation of fatty acid metabolites). Notably, this proposed mechanism may only be relevant under conditions when fatty acid availability is high, and thus this may be very important for the exercise-induced improvements in insulin sensitivity found in obesity. A possible mechanism for increased IMTG synthesis following exercise could be increased expression of the lipogenic enzymes DGAT1 and mGPAT, although whether acute exercise enhances the expression of these lipogenic proteins in human muscle is unknown. In the present study, we tested the hypothesis that a single session of exercise in human subjects would protect against fatty acid–induced insulin resistance the next day. In addition, we examined whether a single session of exercise can enhance partitioning of excess fatty acids toward IMTG synthesis and away from the excessive formation of more metabolically bioactive metabolites basal levels (F infusion of li sitivity index (Figure 3). Ho in fatty acid–i the next day, b levels (Figure minute sessio Acute exercis Despite receiv in g the infus was approxim SED subjects weight, P < 0.001; Figur partitioning of fatty aci fatty acid–induced insu erol concentration was with SED (P < 0.05), and ceramide concent ration This is consistent with exercise will increase th age as IMTG, rather tha muscle glycogen concen EX compared with SED Acute exercise enhances etal muscle. To investiga increased IMTG storag abundance of mGPAT an concentration after exerc and DGAT1 was signifi by approximately 35% ( (Figure 5, A and B). In ad desaturase 1 (SCD1), wh their incorporation into 35%higher in EX compa Skeletal muscle proinflam ering the tight link betw inflammation, and insu Acute Effects of Exercise on Glucose Transport in Diabetics Glycemic Instability in Type II Diabetes is Underestimated Hyperglycemia was present in 13 out of 24hrs in “well controlled” diabetics Type II Diabetic Non-diabetic Praet, Clin Sci, 2006 Acute Exercise Reduces Plasma Glucose KEY POINT: Acute exercise reduces glucose for an extended timeframe in diabetics Praet, Clin Sci, 2006 Acute Exercise Induces GLUT-4 Translocation GLUT-4 Translocation The exercise stimulated movement of GLUT-4 to the plasma membrane remains intact in diabetes 12 10 8 Lean 6 T2DM 4 2 0 Rest Low High Exercise Intensity KEY POINT: Mechanisms underlying lipid-induced insulin resistance can be “bypassed” with exercise Kennedy; Diabetes 48:1192 Acute Exercise Prevents Lipid Induced Insulin Resistance 18 hr overnight lipid infusion 18 hr overnight lipid infusion KEY POINT: Acute exercise prevents lipid induced insulin resistance Shenck and Horowtiz, J Clin Invest 2007 Acute Exercise Prevents Lipid Induced Insulin Resistance KEY POINT: Acute exercise reduces the formation of reactive lipids and promotes proper lipid storage Shenck and Horowtiz, J Clin Invest 2007 Summary Glucose Lipids Ins Blood FAT/CD36 FAT/CD36 P IRS P P FFA PKC AKT DAGs Cytosol PP2 DAGs Ceramides Ceramides PKC P AS160 GLUT-4 vesicle TAGs KEY POINT: Acute exercise enhances both insulin and exercise stimulated glucose transport AS160 P Insulin Sensitivity Acute Exercise and Insulin Sensitivity 15 min at 50%HRmax and 5 min at 85% HRmax 6 5 4 3 2 1 0 control T2DM T2DM-ex Bordenave et al. Diabetes Metab. 2008 ;34:250-7 Chronic Effects of Exercise on Glucose Transport in Diabetics Chronic Exercise Training in Diabetes Benefits of chronic aerobic and resistance training: Direct Improve insulin action and blood glucose control Indirect Improve cardiovascular and metabolic fitness Reduce risk factors for development and progression of type 2 diabetes:  Obesity  Hypertension  High blood cholesterol Response to 100 g of glucose in mild Type 2 Diabetics 20 Plasma Insulin (pmol/l) Plasma Glucose (mmol/l) 12 months of Training 15 10 5 Before After 1600 1200 800 400 Before After 0 0 0 30 60 90 Time (min) 120 150 180 0 30 60 90 120 150 180 Time (min) Holloszy, et al. Acta Medica Scand 1986, 711: 55-65 Benefits of Combined Exercise Sigal R et al Ann Int Med 2007147:357 KEY POINTS Glucose transport into skeletal muscle can be insulin stimulated OR exercise stimulated Insulin stimulates the movement of GLUT-4 to the skeletal muscle membrane to increase glucose transport High lipid environment results in insulin resistance and hyperglycemia Exercise triggers the transport of glucose independent of insulin resistance Acute and chronic exercise reduces glucose for an extended timeframe in diabetics Mechanisms underlying lipid-induced insulin resistance can be “bypassed” by exercise Acute and chronic exercise prevents lipid induced insulin resistance Acute and chronic exercise reduces the formation of reactive lipids and promotes proper lipid storage Acute and chronic exercise enhances both insulin and exercise stimulated glucose transport Exercise Prescription in Diabetes Glucose control Goals of Exercise Training in Diabetes Prevention of diabetes related complications CVD risk factor reduction Diabetes Mellitus: Exercise Testing See GETP11 Chapter 2, ACSM Preparticipation Algorithm, for guidance on exercise testing. ECG stress testing may be indicated for individuals with DM, who have been sedentary and/or desire vigorous intensity activities. Silent ischemia in individuals with DM often goes undetected; therefore, annual CVD risk factor assessments should be conducted. Particular attention should be paid to the mode of exercise testing based on the presence of complications (”opaties”) Diabetes Mellitus: Exercise Prescription Maximizing the cardiovascular benefits resulting from exercise is a key outcome for both types of diabetes; therefore, an exercise frequency of greater than 3 d · wk−1 is suggested. Healthy weight loss and maintenance of appropriate body weight are often more pressing issues for those with T2DM and prediabetes. Resistance exercise confers similar metabolic benefits to aerobic exercise in individuals with T2DM. There is some evidence that a combination of aerobic and resistance exercise improves blood glucose control more than either modality alone. Individualized according to medication schedule, presence and severity of diabetic complications and goals of and expected benefits of the exercise program. Recommendations for Exercise Programming Include endurance and resistance exercise for developing and maintaining cardiorespiratory fitness, body composition, and muscular strength and endurance. Food intake must be considered for anyone on hypoglycemic medication: 1 h of exercise requires an additional 15 g of CHO either before or after exercise Consume an additional 15 to 30 g CHO for each additional hour when performing vigorous or longduration (>60 min) exercise What to watch for… Glucose utilization = Glucose production = NORMOglycemia Moderate Exercise Blood Glucose (mg/dl) 100 80 60 Under normal conditions in individuals without diabetes, precise co-ordination of hormonal and metabolic events result in maintenance of glucose homeostasis… 40 20 Rates of Glucose Entry and Removal from Blood (mg kg-1 min-1) 0 5 4 3 Glucose utilization Glucose production 2 1 0 -3 0 0 Time3(min) 0 60 What to watch for…. Glucose utilization > Glucose production = HYPOglycemia Moderate Exercise Blood Glucose (mg/dl) 100 80 60 Insulin and counterregulatory hormone concentrations in people with diabetes do not respond to exercise in a normal manner 40 20 Imbalance between peripheral glucose utilization and hepatic glucose production Rates of Glucose Entry and Removal from Blood (mg kg-1 min-1) 0 5 Rates of Glucose Entry and Removal from the Blood 4 3 Glucose utilization 2 (mg kg-1 min-1Glucose ) production 1 0 -3 0 0 30 60  The most common problem for diabetics who exercise. Exercise-induced hypoglycemia, may last as long as 48 hours after exercise Hypoglycemi a blood glucose