Reviews/Commentaries/ADA Statements CONSENSUS STATEMENT

Physical Activity/ and Type 2 Diabetes A consensus statement from the American Diabetes Association

1,2,3 5 RONALD J. SIGAL, MD, MPH CARMEN CASTANEDA-SCEPPA, MD, PHD larger extent than exercise volume (r ϭ 2,3 6 GLEN P. KENNY, PHD RUSSELL D. WHITE, MD Ϫ0.46, P ϭ 0.26). These results provide 4 DAVID H. WASSERMAN, PHD support for encouraging type 2 diabetic individuals who are already exercising at moderate intensity to consider increasing or decades, exercise has been consid- the progression from IGT to diabetes (5). the intensity of their exercise in order to ered a cornerstone of diabetes man- Therefore, there is firm and consistent ev- obtain additional benefits in both aerobic F agement, along with diet and idence that programs of increased physi- fitness and glycemic control. medication. However, high-quality evi- cal activity and modest weight loss reduce dence on the importance of exercise and the incidence of type 2 diabetes in indi- fitness in diabetes was lacking until recent viduals with IGT. PHYSICAL ACTIVITY, years. The present document summarizes AEROBIC FITNESS, AND the most clinically relevant recent ad- EFFECTS OF STRUCTURED RISK OF CARDIOVASCULAR vances related to people with type 2 dia- EXERCISE INTERVENTIONS AND OVERALL MORTALITY — betes and the recommendations that ON GLYCEMIC CONTROL Large cohort studies have found that follow from these. Our recently published AND BODY WEIGHT IN higher levels of habitual aerobic fitness technical review on physical activity/ TYPE 2 DIABETES — Boule´ et al. and/or physical activity are associated exercise and type 2 diabetes (1) includes (6) undertook a systematic review and with significantly lower subsequent car- greater detail on individual studies, on meta-analysis on the effects of structured diovascular and overall mortality (8–10), prevention of diabetes, and on the physi- exercise interventions in clinical trials of to a much greater extent than could be Ն explained by glucose lowering alone. For ology of exercise. 8 weeks duration on HbA1c (A1C) and The present statement focuses on body mass in people with type 2 diabetes. example, Church et al. (8) found that men type 2 diabetes. Issues primarily germane Postintervention A1C was significantly in the lowest, second, and third quartiles to type 1 diabetes will be covered in a lower in exercise than control groups of cardiorespiratory fitness had 4.5-, 2.8-, subsequent technical review and ADA (7.65 vs. 8.31%, weighted mean differ- and 1.6-fold greater risk for overall mor- Statement. The levels of evidence used are ence Ϫ0.66%; P Ͻ 0.001). In contrast, tality than men in the highest quartile of defined by the ADA in ref. 2. postintervention body weight did not dif- cardiorespiratory fitness, even after ad- fer between the exercise and control justment for age, examination year, base- PHYSICAL ACTIVITY AND groups. Meta-regression confirmed that line cardiovascular disease (CVD), PREVENTION OF TYPE 2 the beneficial effect of exercise on A1C hypercholesterolemia, hypertriglyceride- DIABETES — Two randomized trials was independent of any effect on body mia, BMI, hypertension, parental CVD, each found that lifestyle interventions in- weight. Therefore, structured exercise smoking, and baseline fasting glucose lev- cluding ϳ150 min/week of physical ac- programs had a statistically and clinically els. Essentially all of the association be- tivity and diet-induced weight loss of significant beneficial effect on glycemic tween higher BMI and higher mortality 5–7% reduced the risk of progression control, and this effect was not primarily was explained by confounding with car- from impaired glucose tolerance (IGT) to mediated by weight loss. A subsequent diorespiratory fitness; there was no differ- type 2 diabetes by 58% (3,4). A cluster- meta-analysis by the same authors (7) ence in mortality among normal-weight, randomized trial found that diet alone, showed that exercise intensity predicted overweight, and obese men after adjust- exercise alone, and combined diet and ex- postintervention weighted mean differ- ment for cardiorespiratory fitness. ercise were equally effective in reducting ence in A1C (r ϭϪ0.91, P ϭ 0.002) to a In the same cohort, it was shown that ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● among moderately fit subjects (21st– 60th percentile for age) whose only exer- From the 1Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; the 2School of Human Kinetics, University of Ottawa, Ottawa, Ontario, Canada; the 3Clinical Epidemiology Program, Ottawa cise was walking, the mean time spent per Health Research Institute, Ottawa, Ontario, Canada; the 4Department Of Molecular Physiology and Bio- week on exercise was 130 min for men physics, Vanderbilt University, Nashville, Tennessee; the 5Jean Mayer USDA Human Nutrition Research and 148 min for women (11). These times Center on Aging, Tufts University, Boston, Massachusetts; and the 6Department of Community and Family are consistent with recommendations Medicine, Truman Medical Center-Lakehead, University of Missouri-Kansas City School of Medicine, Kansas from the U.S. Surgeon General (12) and City, Missouri. Address correspondence and reprint requests to Ronald J. Sigal, Clinical Epidemiology Program, Ottawa other respected bodies (13–15) stating Health Research Institute, 1053 Carling Ave., Ottawa, Ontario, Canada K1Y 4E9. E-mail: [email protected]. that 150 min/week of moderate-intensity Abbreviations: CAD, coronary artery disease; CVD, cardiovascular disease; ECG, electrocardiogram; exercise should be accumulated. Moder- IGT, impaired glucose tolerance. ately fit subjects whose only exercise was A table elsewhere in this issue shows conventional and Syste`me International (SI) units and conversion factors for many substances. jogging or running reported a mean of 90 DOI: 10.2337/dc06-9910 min/week for men and 92 min/week for © 2006 by the American Diabetes Association. women. These times are consistent with

DIABETES CARE, VOLUME 29, NUMBER 6, JUNE 2006 1433 Exercise in type 2 diabetes an alternative and equally valid recom- obese people often have difficulty per- sus no significant change in control mendation for 30 min of vigorous activity forming sufficient exercise to create a subjects. One of these trials had a second three times a week. large energy deficit, and it is relatively phase (months 7–12), where training was To our knowledge, no meta-analysis easy to counterbalance increased energy home based rather than facility based of the effects of exercise training on lipids expenditure through exercise by eating (34). Body composition changes were or blood pressure in people with diabetes more or becoming less active outside of maintained, but exercise intensity and ad- has been published. In the general, pre- exercise sessions (22). However, in a ran- herence were lower than in the first 6 dominantly nondiabetic population, the domized trial, high-volume aerobic exer- months and the A1C difference between effects of exercise training on blood pres- cise (700 kcal/day, ϳ1 h/day of moderate- groups became statistically nonsignifi- sure (16) and lipids (17) are relatively intensity ) produced at cant. Other published studies of modest. Greater increases in HDL choles- least as much fat loss as the equivalent resistance exercise in type 2 diabetic par- terol and decreases in plasma triglycerides degree of caloric restriction and with ticipants have used less intense exercise have been seen with exercise programs greater resulting improvements in insulin regimens (35–40). All showed beneficial that are more rigorous in terms of both sensitivity (23). effects of the resistance exercise program volume and intensity than those that have The optimal volume of exercise to but to a lesser extent than the Dunstan et been evaluated in diabetic subjects (18). achieve sustained major weight loss is al. (32) and Castaneda et al. (33) trials. Potential mechanisms through which ex- probably much larger than needed to ercise could improve cardiovascular achieve improved glycemic control and health were reviewed by Stewart (19). cardiovascular health. In observational Safety of resistance training These include decreased systemic inflam- studies (24–27), individuals who suc- Some medical practitioners have con- mation, improved early diastolic filling cessfully maintain large weight loss over cerns about the safety of higher-intensity (reduced diastolic dysfunction), im- at least a year have typically performed resistance exercise in middle-aged and proved endothelial vasodilator function, ϳ7 h/week of moderate- to vigorous- older people who are at risk of CVD. Of- and decreased abdominal visceral fat intensity exercise. Two randomized trials ten, the main concern is that the acute accumulation. found that higher exercise volumes rises in blood pressure associated with (2,000 and 2,500 kcal/week) produced higher-intensity resistance exercise might FREQUENCY OF EXERCISE —The greater and more sustained weight loss be harmful, possibly provoking stroke, U.S. Surgeon General’s report (12) rec- than lower exercise volumes (1,000 kcal/ myocardial ischemia, or retinal hemor- ommended that most people accumulate week) (28,29). rhage. We have found no evidence that Ն30 min of moderate-intensity activity Because of the increased evidence for resistance training actually increases on most, ideally all, days of the week. health benefits from resistance training these risks. No serious adverse events However, most clinical trials evaluating during the past 10–15 years, the Ameri- have been reported in any research study exercise interventions in people with type can College of Sports Medicine (ACSM) of resistance training in patients with type 2 diabetes have used a three-times-per- now recommends that resistance training 2 diabetes, although the total number of week frequency (6), and many people be included in fitness programs for subjects enrolled in these studies was find it easier to schedule fewer longer ses- healthy young and middle-aged adults small (32,33,35–37,40). A review of 12 sions rather than five or more weekly (13), older adults (30), and adults with resistance exercise studies in a total of 246 shorter sessions. The effect of a single type 2 diabetes (15). With increased age, male cardiac rehabilitation patients found bout of aerobic exercise on insulin sensi- there is a tendency for progressive de- no angina, ST depression, abnormal he- tivity lasts 24–72 h depending on the du- clines in muscle mass, leading to “sar- modynamics, ventricular dysrhythmias, ration and intensity of the activity (20). copenia,” decreased functional capacity, or other cardiovascular complications Because the duration of increased insulin decreased resting metabolic rate, in- (41). A study of 12 men with known cor- sensitivity is generally not Ͼ72 h, we rec- creased adiposity, and increased insulin onary ischemia and electrocardiogram ommend that there should not be more resistance, and resistance training can (ECG) changes inducible by moderate than 2 consecutive days without aerobic have a major positive impact on each of aerobic exercise found that even maxi- physical activity. The effect of resistance these (30). Resistance exercise improves mal-intensity resistance exercise did not exercise training on insulin sensitivity insulin sensitivity to about the same ex- induce ECG changes (42). Therefore, may last somewhat longer (21), perhaps tent as aerobic exercise (31). moderate- to high-intensity resistance because some of its effects are mediated training was found to be safe even in men by increases in muscle mass. RESISTANCE TRAINING at significant risk of cardiac events. While it is well known that blood EXERCISE FOR WEIGHT Studies of resistance training in type pressure rises while lifting a heavy weight, LOSS AND WEIGHT 2 diabetes it is often not appreciated that blood pres- MAINTENANCE — The most suc- Two clinical trials provided the strongest sure can also rise considerably in healthy cessful programs for long-term weight evidence for the value of resistance train- older people performing aerobic exercise. control have involved combinations of ing in type 2 diabetes (32,33). In both Benn et al. (43) demonstrated that in diet, exercise, and behavior modification studies, the average age of participants healthy older men, the myocardial (22). Exercise alone, without concomi- was 66 years, and the resistance-training demands of high-intensity resistance ex- tant dietary caloric restriction and behav- regimen involved multiple at ercise were comparable to those occasion- ior modification, tends to produce only high intensity (three sets, three times per ally needed for activities of daily living, modest weight loss of ϳ2 kg. Weight loss week), and absolute A1C declined 1.1– such as climbing stairs, walking up a hill, is typically this small primarily because 1.2% in resistance-training subjects ver- or carrying 20–30 lb of groceries.

1434 DIABETES CARE, VOLUME 29, NUMBER 6, JUNE 2006 Sigal and Associates

FLEXIBILITY EXERCISE — Flexi- Ten-year CVD risk can be estimated using vided the patient feels well, the patient is bility exercise (stretching) has frequently the UKPDS (U.K. Prosepctive Diabetes adequately hydrated, and urine and/or been recommended as a means of increas- Study) Risk Engine (50) (http://www.dtu. blood ketones are negative, it is not neces- ing range of motion and hopefully ox.ac.uk/index.html?maindoc%20ϭ%20/ sary to postpone exercise based solely on reducing risk of injury. However, two sys- riskengine/), while 30-year risk of a wide hyperglycemia. tematic reviews found that flexibility ex- variety of outcomes, including CVD, can be ercise did not reduce risk of exercise- estimated using the American Diabetes As- Hypoglycemia induced injury (44,45). Most studies sociation’s Diabetes PHD (Personal Health In individuals taking insulin and/or insu- included in these systematic reviews eval- Decisions) (51) (http://diabetes.org/ lin secretagogues, physical activity can uated younger subjects undertaking very diabetesPHD). The lower the absolute CAD cause hypoglycemia if medication dose or vigorous activity programs, such as those risk, the higher the likelihood of a false- carbohydrate consumption is not altered. in military basic training; these results positive test. A recent systematic review for This is particularly so at times when ex- may not be generalizable to older sub- the U.S. Preventive Services Task Force ogenous insulin levels are at their peaks jects. Flexibility exercise has been suc- came to the conclusion that stress tests and if physical activity is prolonged. Hy- cessfully used in clinical trials as a should usually not be recommended to de- poglycemia would be rare in diabetic in- “placebo” exercise (32,46), since there is tect ischemia in asymptomatic individuals dividuals who are not treated with insulin no evidence that flexibility exercise affects at low CAD risk (Ͻ10% risk of a cardiac or insulin secretagogues. Previous ADA metabolic control or quality of life. One event over 10 years) because the risks of guidelines suggested that added carbohy- small randomized trial (n ϭ 19) found subsequent invasive testing triggered by drate should be ingested if preexercise that range-of-motion exercises modestly false-positive tests outweighed the expected glucose levels are Ͻ5.6 mmol/l (100 mg/ decreased peak plantar pressures (47). benefits from detection of previously unsus- dl) (55). We agree with this recommen- We found no studies that directly evalu- pected ischemia (52,53). dation for individuals on insulin and/or ated whether flexibility training reduced There is little or no evidence to guide an insulin secretagogue. However, the the risk of ulceration or injury in people practitioners in terms of whether stress revised guidelines clarify that supple- with diabetes. Therefore, we feel that testing before undertaking resistance mentary carbohydrate is generally not there is insufficient evidence to recom- training is necessary. One might ask necessary for individuals treated only mend for or against flexibility exercise as a whether such testing should use resis- with diet, metformin, ␣-glucosidase in- routine part of the exercise prescription. tance exercise rather than the usual aero- hibitors, and/or thiazolidinediones with- bic exercise during a stress test in such out insulin or a secretagogue. We found EVALUATION OF THE circumstances. Very few test centers no published studies examining re- DIABETIC PATIENT BEFORE would currently be equipped for such sponses to exercise in subjects taking RECOMMENDING AN testing, and such tests have not been stan- pramlintide (synthetic amylin analog) or EXERCISE PROGRAM — For a dardized. In contrast, aerobic exercise exenatide (incretin analog). Neither is more detailed review on this subject, see stress testing is widely available, stan- likely to cause hypoglycemia when used ref. 48. Before beginning a program of dardized, and of proven prognostic value. as monotherapy or combined with only physical activity more vigorous than brisk metformin or a thiazolidinedione. How- walking, people with diabetes should be EXERCISE IN THE PRESENCE ever, patients taking either of these drugs assessed for conditions that might be as- OF NONOPTIMAL in combination with insulin or a secreta- sociated with increased likelihood of CVD GLYCEMIC CONTROL gogue may need to take additional carbo- or that might contraindicate certain types hydrate before physical activity and/or of exercise or predispose to injury, such as Hyperglycemia reduce doses of insulin or secretagogue to severe autonomic neuropathy, severe pe- When people with type 1 diabetes are de- avoid hypoglycemia. For a detailed dis- ripheral neuropathy, and preproliferative prived of insulin for 12–48 h and ketotic, cussion of medication adjustments to re- or proliferative retinopathy. The patient’s exercise can worsen the hyperglycemia and duce risk of hypoglycemia, see ref. 56. age and previous physical activity level ketosis (54). Previous ADA exercise posi- Concomitant medications other than should be considered. tion statements suggested that physical ac- hypoglycemic agents. Diabetic patients The role of stress testing before begin- tivity be avoided if fasting glucose levels are frequently take diuretics, ␤-blockers, ning an exercise program is controversial. Ͼ13.9 mmol/l (Ͼ250 mg/dl) and ketosis is ACE inhibitors, aspirin, and lipid- There is no evidence that such testing is rou- present and that it be performed with cau- lowering agents. In most type 2 diabetic tinely necessary for those planning moder- tion if glucose levels are Ͼ16.7 mmol/l (300 individuals, medications will not interfere ate-intensity activity such as walking, but it mg/dl), even if no ketosis is present (55). with the physical activities they choose to should be considered for previously seden- We agree that vigorous activity should perform, but patients and health care pro- tary individuals at moderate to high risk of probably be avoided in the presence of ke- viders should be aware of potential prob- CVD who want to undertake vigorous aer- tosis. However, the recommendation to lems to minimize their impact. Diuretics, obic exercise exceeding the demands of ev- avoid physical activity if plasma glucose is especially in higher doses, can interfere eryday living (49). The prevalence of both Ͼ300 mg/dl, even in the absence of ketosis, with fluid and electrolyte balance. symptomatic and asymptomatic coronary is probably more cautious than necessary ␤-Blockers can blunt the adrenergic artery disease (CAD) is greater in diabetic for a person with type 2 diabetes, especially symptoms of hypoglycemia, possibly in- individuals compared with nondiabetic in- in a postprandial state. In the absence of creasing risk of hypoglycemia unaware- dividuals of the same age-group. However, very severe insulin deficiency, light- or ness. They can reduce maximal exercise many younger diabetic patients have rela- moderate-intensity exercise would tend to capacity to ϳ87% of what it would be tively low absolute risk for a coronary event. decrease plasma glucose. Therefore, pro- without ␤ blockade (57) through their

DIABETES CARE, VOLUME 29, NUMBER 6, JUNE 2006 1435 Exercise in type 2 diabetes negative inotropic and chronotropic ef- cise, postural hypotension, impaired with modest energy restriction. Level of fects. However, most people with type 2 thermoregulation due to impaired skin evidence: A (3,4,68,69). diabetes do not choose to exercise at very blood flow and sweating, impaired night high intensity, so this reduction of maxi- vision due to impaired papillary reaction, Aerobic exercise mum capacity is generally not problem- and impaired thirst, which increases the The amount and intensity recommended atic. In people with CAD, ␤ blockade risk of dehydration and gastroparesis for aerobic exercise vary according to actually increases exercise capacity by re- with unpredictable food delivery (60). goals. ducing coronary ischemia (58). For addi- Autonomic neuropathy is also strongly tional discussion on the impact of associated with CVD in people with dia- ● To improve glycemic control (6,7), concomitant medications on physical ac- betes (62,63). Individuals with diabetic assist with weight maintenance, and tivity, see ref. 48. autonomic neuropathy should undergo reduce risk of CVD (9,10), we recom- cardiac investigation before beginning mend at least 150 min/week of moder- EXERCISE IN THE PRESENCE physical activity more intense than that to ate-intensity aerobic physical activity OF SPECIFIC LONG-TERM which they are accustomed. Some experts (40–60% of VO2max or 50–70% of COMPLICATIONS OF advocate thallium scintigraphy as the pre- maximum heart rate) and/or at least 90 DIABETES — There is a paucity of re- ferred screening technique for CVD in min/week of vigorous aerobic exercise Ͼ Ͼ search on the risks and benefits of exercise this high-risk population (60). ( 60% of VO2max or 70% of maxi- in the presence of diabetes complications. mum heart rate). The physical activity Therefore, recommendations in this sec- Microalbuminuria and nephropathy should be distributed over at least 3 tion are based largely on “expert opinion.” Physical activity can acutely increase uri- days/week and with no more than 2 nary protein excretion. The magnitude of consecutive days without physical ac- Retinopathy this increase is in proportion to the acute tivity. Level of evidence: A (6,7). Exercise and physical activity are not increase in blood pressure. This finding has ● Performing Ն4 h/week of moderate to known to have any adverse effects on vi- led some experts to recommend that people vigorous aerobic and/or resistance ex- sion or the progression of nonprolifera- with diabetic kidney disease perform only ercise physical activity is associated tive diabetic retinopathy or macular light or moderate exercise, such that blood with greater CVD risk reduction com- edema (59). This applies to both resis- pressure during exercise would not rise to pared with lower volumes of activity tance and aerobic training. However, in more than 200 mmHg (64). However, there (10). Level of evidence: B (9,10). the presence of proliferative or severe is no evidence from clinical trials or cohort ● For long-term maintenance of major nonproliferative diabetic retinopathy, studies demonstrating that vigorous exer- weight loss (Ն13.6 kg/30 lb), larger vigorous aerobic or resistance exercise cise increases the rate of progression of dia- volumes of exercise (7 h/week of mod- may be contraindicated because of the po- betic kidney disease. Several randomized erate or vigorous aerobic physical activ- tential risk of triggering vitreous hemor- trials in animals with diabetes and protein- ity) may be helpful (24–27,70). Level of rhage or retinal detachment (59). We uria showed that aerobic exercise training evidence: B (24–27,70). found no research studies providing guid- decreased urine protein excretion (65,66), ance as to an appropriate time interval be- possibly in part due to improved glycemic Resistance exercise tween successful laser photocoagulation control, blood pressure, and insulin sensi- In the absence of contraindications, peo- and initiation or resumption of resistance tivity. Resistance training also may be of ple with type 2 diabetes should be en- exercise. Ophthalmologists, with whom benefit in terms of muscle mass, nutritional couraged to perform resistance exercise one of us (C.C.-S.) consulted, suggested status, functional capacity, and glomerular three times a week, targeting all major waiting 3–6 months after laser photoco- filtration rate (67). Because of these encour- muscle groups, progressing to three sets agulation before initiating or resuming aging findings, we believe there may be no of 8–10 repetitions at a weight that can- this type of exercise. need for any specific exercise restrictions for not be lifted more than 8–10 times (8–10 people with diabetic kidney disease. How- RM). Level of evidence: A (32,33). To en- Peripheral neuropathy ever, because microalbuminuria and pro- sure resistance exercises are performed We are unaware of research studies assess- teinuria are associated with increased risk correctly, maximize health benefits, and ing the risk of exercise-induced injury in for CVD, it is important to perform an exer- minimize the risk of injury, we recom- people with peripheral sensory neuropathy. cise ECG stress test in previously sedentary mend initial supervision and periodic re- Common sense, however, would indicate individuals with these conditions before be- assessments by a qualified exercise that decreased pain sensation in the extrem- ginning exercise significantly more intense specialist, as was done in the clinical trials ities would result in increased risk of skin than the demands of everyday living. (32,33). breakdown and infection and of Charcot joint destruction. Therefore, in the presence RECOMMENDATIONS — Levels Prevention of hypoglycemia of severe peripheral neuropathy, it may be of evidence used are those defined by the Those who take insulin or secretagogues best to encourage non–weight-bearing ac- ADA in ref. 2. should check capillary blood glucose be- tivities such as swimming, bicycling, or arm fore, after, and several hours after com- exercises (60,61). Lifestyle measures for prevention of pleting a session of physical activity, at type 2 diabetes least until they know their usual glycemic Autonomic neuropathy In people with IGT, a program of weight responses to such activity. For those who Autonomic neuropathy can increase the control is recommended, including at show a tendency to hypoglycemia during risk of exercise-induced injury by de- least 150 min/week of moderate to vigor- or after exercise, several strategies can be creasing cardiac responsiveness to exer- ous physical activity and a healthful diet used. Doses of insulin or secretagogues

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