Glycemic control in type 2 diabetes. Exercise prescription in type 2 diabetes treatment. Target for diabetes intervention.

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1 Exercise prescription in type 2 diabetes treatment Glycemic control in type 2 diabetes Prof. L.J.C. van Loon The level of glycemia is associated with the development of cardiovascular complications Glycemic control is fundamental to type 2 diabetes treatment ADA; EASD; IDF Maastricht University Medical Centre+ Maastricht, the Netherlands Maastricht, February 27, 21 Target for diabetes intervention Therapeutic targets should be aimed at reducing post-prandial blood glucose excursions Standard parameters for the assessment of glycemic control do not provide sufficient information on post-prandial hyperglycemia Glycemic control Continuous Glucose Monitoring System Basal blood glucose and HbA1c content Self-monitored blood glucose concentration Maran et al., Diabetes Care, 21 1

2 Continuous Glucose Monitoring System Glycemic control Glucose concentration (mmol/l) 14 Control Type 2 diabetes 4 7: 11: 15: 19: 23: 3: 7: Time (h) van Dijk et al., Diabetes Res Clin Pract, 211 Daily glycemic control Glycemic control in type 2 diabetes Prevalence of hyperglycemia (% / 24 h) 5 A control type 2 diabetes B HbA1c <7%, (<53 mmol/mol) control type 2 diabetes Under standardized dietary conditions long-standing type 2 diabetes patients are in a state of hyperglycemia throughout the greater part of the day Oral blood glucose lowering medication does not provide ample protection against (post-prandial) hyperglycemia van Dijk et al., Diabetes Res Clin Pract, 211 Praet et al., Clinical Science, 2 Type 2 diabetes treatment The type 2 diabetes epidemic Oral blood glucose lowering medication Exogenous insulin therapy % of the increase in the prevalence of type 2 diabetes and obesity in the United States during the latter half of the 2th century must be attributed to a changing environment interacting with genes, because % of the human genome has changed during this time period. Booth et al., JAP, 2 2

3 Lifestyle changes Diabetes prevention - lifestyle Finnish Diabetes Prevention Study Tuomiletho et al., NEJM, 21 5% reduced risk type 2 diabetes Diabetes Prevention Program Knowler et al., NEJM, 22 Lifestyle > Metformin > Placebo Da Qing Diabetes Prevention Pan et al., Diabetes Care, % reduced risk type 2 diabetes Malmö Preventive Trial Eriksson et al., Diabetologia, 199 Significant reduction mortality Diabetes treatment Exercise in diabetes treatment Diabetes cohort studies report regular exercise to be associated with a 4-7% lower mortality rate for to 14 years Hu F. et al., Ann. Intern. Med., 1999 Wei et al., Ann. Intern. Med., 2 Tanasescu., Circulation, 23 Hu G. et al., Circulation, 24 whole-body insulin sensitivity (-%) glycemic control (HbA1c : -.7 %) oxidative capacity (VO 2max : -15%) cardiovascular risk profile (LDL, TG, BP) fat mass and body composition Boulé et al., Diabetologia, 23; Sigal et al., Diabetes Care, 2; Praet et al., J Appl Physiol, 27; Umpierre et al., JAMA, 211; Chudyk et al., Diabetes Care, 211 Position statement A Exercise training and glycemic control To improve glycemic control, assist with weight maintenance, and reduce risk of CVD, at least 15 min/wk of moderate-intensity aerobic physical activity (5-7% HR max ) is recommended and/or at least 9 min/wk of vigorous aerobic exercise (7% HR max ). The physical activity should be distributed over at least 3 days/wk and with no more than 2 consecutive days without physical activity. ADA 27 - Standards of Medical Care in Diabetes Diabetes Care, 27 The improvements in glycemic control with exercise training are largely attributed to the cumulative effects of transient improvements in glucose tolerance following each successive bout of exercise Goodyear and Kahn, Ann Rev Med, 199 Effects of training on glycemic control may be lost entirely - days after cessation of training Praet and van Loon, J Appl Physiol, 27 3

4 Endurance type exercise Position statement A An acute bout of endurance type exercise improves insulin sensitivity for a period up to 4 h. Schneider et al., Diabetologia, 194 Devlin et al., Diabetes, 197 Cusi et al., J. Clin. Invest., 2 Wojtaszewski et al., Diabetes, 2 To improve glycemic control, assist with weight maintenance, and reduce risk of CVD, at least 15 min/wk of moderate-intensity aerobic physical activity (5-7% HR max ) is recommended and/or at least 9 min/wk of vigorous aerobic exercise (7% HR max ). The physical activity should be distributed over at least 3 days/wk and with no more than 2 consecutive days without physical activity. ADA 27 - Standards of Medical Care in Diabetes Diabetes Care, 27 Acute exercise in type 2 diabetes Exercise as therapy Hyperglycemia (duration %/24h) Based on baseline aerobic fitness, level of co-morbidities, appendicular skeletal muscle mass and strength, patients should be provided with a fitting exercise intervention program to optimize its therapeutic value. Praet et al., Med. Sci. Sports Exerc., 2 Exercise modalities Type of exercise - type of exercise - intensity of exercise - duration of exercise - frequency - timing Lance Armstrong Jay Cutler 4

5 Endurance type exercise Endurance type exercise An acute bout of endurance type exercise improves insulin sensitivity for a period up to 4 h. Long-term weight loss and weight control Feasibility in elderly patients with type 2 diabetes Devlin et al., Diabetes, 197 Mikines et al., AJP, 19 Feasibility in type 2 diabetes with co-morbidities Perseghin et al., NEJM, 199 Long-standing type 2 diabetes Aging and sarcopenia Loss of skeletal muscle mass, strength, and function Muscle weakness with aging is both cause as well as a consequence Cardiovascular co-morbidities of type 2 diabetes Exercise intolerance Proportional relationship between muscle mass Low adherence and compliance and glucose disposal capacity Fang et al., 25 Sayer et al., 25 Volpato et al., 22 Park et al., 2; Willey et al., 23 Thomas et al., 24 Meyer et al., 199 Resistance type exercise Resistance type exercise Muscle mass Progressive resistance type exercise training offers a safe and effective alternative to endurance type exercise training Muscle strength Functional capacity An acute bout of resistance exercise improves insulin sensitivity to a similar extent as endurance exercise Fluckey et al.,1994 Fenicchia et al., 24 Koopman et al., 25 5

6 Type of exercise, design Type of exercise, intervention 45 min, 75% 1 RM randomized, 3-way crossover 45 min, 5% Wmax van Dijk et al., Diabetologia, 2 Prevalence of hyperglycemia 24-h glycemic profiles Control: no exercise Resistance- type exercise Endurance- type exercise Control: no exercise Resistance- type exercise Endurance- type exercise 14 5 Prevalence of hyperglycemia (% / 24 h) Blood glucose concentration (mmol/l) 1 9: : 15: 1: 21: : 3: : 9: : 3 2 # : 4 IGT OGLM INS Time van Dijk et al., Diabetologia, 2 van Dijk et al., Diabetologia, 2 Resistance type exercise - improved glucose disposal - glycogen storage capacity - GLUT-4 content - glycemic control (HbA1c: -1.1%) - insulin sensitivity - oral glucose tolerance - cardiovascular risk profile (HDL, LDL, BP) - body composition Castaneda et al., 22; Dunstan et al., 199, 22; Ishii et al., 199, Cauza et al., 25;Willey et al., 23 Church et al., JAMA, 2

7 Position statement B Exercise modalities In the absence of contraindications, people with type 2 diabetes should be encouraged to perform resistance exercise 3 times a week, targeting all major muscle groups, progressing to 3 sets of - repetitions at a weight that cannot be lifted more than - times. ADA 27 - Standards of Medical Care in Diabetes Diabetes Care, 27 - type of exercise - intensity of exercise - duration of exercise - frequency - timing - interaction with pharmaceuticals - interaction with food intake Low versus high-intensity exercise Exercise intensity and glycemic control 35% Wmax 3 7% Wmax Manders et al., Med Sci Sports Exerc, 2 Manders et al., Med Sci Sports Exerc, 2 Exercise intensity and insulin sensitivity ~7 5% VO2max ~55 5% VO2max Newsom et al., Diabetes Care, 213 7

8 Exercise modalities Study design - type of exercise - intensity of exercise - duration of exercise - frequency - timing DAILY NON- DAILY CONTROL randomized, 3-way crossover Day 1 Day 2 Day 3 4 h analysis period (3 min) (3 min) ( min) : : 1: : : : 1: : : : van Dijk et al., Diabetes Care, 2 Prevalence of hyperglycemia (% of the time) Prevalence of hyperglycemia CONTROL: no exercise NON-DAILY exercise DAILY exercise Total 4 h First 24 h Second 24 h Are the blood glucose lowering effects equal for all type 2 diabetic patients? van Dijk et al., Diabetes Care, 2 Individual response to exercise Well-controlled and suboptimally controlled patients delta glucose concentration (mmol/l) individual change in average glucose concentration over 24 h period following exercise A prevalence of hyperglycemia (hour/day) B -3:24 h:min control exercise -1:43 h:min blood glucose concentration (mmol/l) -. mmol/l -1.2 mmol/l Hba1c <7% HbA1c 7% Hba1c <7% HbA1c 7% subject

9 Exercise or simply more habitual physical activity to improve blood glucose homeostasis? Study design Study protocol day 1 day 2 day 3 Exercise Habitual Physical Activity 45 min 15 min 15 min 15 min Control Blood 24-h blood glucose 24-h glycemic control Blood glucose (mmol/l) 1 14 Control Habitual Physical Activity Exercise 4 :3 11:3 14:3 17:3 2:3 23:3 2:3 5:3 :3 Hyperglycemia (hours/day) Control Habitual Physical Activity Exercise Time (h) van Dijk et al., Diabetes Care, 213 van Dijk et al., Diabetes Care, 213 9

10 Postprandial glycemic control Insulin iauc Blood glucose (mmol/l) 1 14 Control Habitual Physical Activity Exercise 4 :3 11:3 14:3 17:3 2:3 23:3 2:3 5:3 :3 Time (h) insulin iauc (mu/ml/11h) Control -17±5% Habitual Physical Activity -33±4% Exercise van Dijk et al., Diabetes Care, 213 van Dijk et al., Diabetes Care, 213 Summary Summary II Hyperglycemia is highly prevalent throughout the day in type 2 diabetes patients. Exercise strongly reduces the prevalence of hyperglycemia throughout the day. Resistance and endurance-type exercise are equally effective in improving daily blood glucose homeostasis. Higher intensity exercise is not more effective than lower intensity exercise to improve daily blood glucose homeostasis. When total work is being matched, daily exercise does not further improve glycemic control, when compared to exercise performed every other day. Even well-controlled patients can benefit from the glucose lowering properties of exercise. Summary III Exercise prescription Habitual physical activity attenuates the postprandial rise in blood glucose and insulin concentrations. When matched for duration, exercise is more effective than more habitual physical activity to improve glycemic control. The volume of physical activity seems to determine the improvements in glycemic control.

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