Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial.

Context The benefits of exercise in improving glycemic control in patients with type 2 diabetes are well documented. Previous studies have examined aerobic or resistance exercise alone but not in combination. Contribution This randomized, controlled trial showed better reduction in hemoglobin A1c values in patients who followed a combined aerobic exercise and resistance training program 3 times weekly than in patients who followed a program of either exercise type alone. Caution Patients in the combined exercise group had a longer duration of exercise than those in the other exercise groups; the study thus does not permit definitive conclusions about whether the benefits were due to longer exercise duration or to the combined exercise training. The Editors Physical activity is important in the management of type 2 diabetes mellitus. Systematic reviews (14) found that structured aerobic exercise (walking, jogging, or cycling) or resistance exercise (weightlifting) reduced the absolute hemoglobin A1c value by about 0.6%. The hemoglobin A1c value reflects the mean plasma glucose concentration over the previous 2 to 3 months. A 1% absolute decrease in the hemoglobin A1c value is associated with a 15% to 20% decrease in major cardiovascular events (5) and a 37% reduction in microvascular complications (6). The only study that compared combined aerobic and resistance training with aerobic training alone found no differences in hemoglobin A1c values between the groups, but the low average baseline hemoglobin A1c value (6.7%) and small sample (9 to 10 persons per group) limited the power to detect a difference (7). We designed the DARE (Diabetes Aerobic and Resistance Exercise) clinical trial to determine the effects of aerobic and resistance training alone versus a sedentary control group, and the incremental effects of doing both types of exercise (combined exercise training) versus aerobic or resistance training alone, on glycemic control and other risk factors for cardiovascular disease. We report our results for the primary outcome (change in hemoglobin A1c value from baseline to the end of the intervention) and for the secondary outcomes of plasma lipid levels, blood pressure, and body composition. We hypothesized that the decrease in hemoglobin A1c value would be greater in the aerobic and resistance training groups than the control group and would be even greater in the combined exercise training group than the aerobic or resistance training group. Methods Design We conducted a 26-week, single-center, randomized, controlled trial with a parallel-group design. After a 4-week run-in phase, previously inactive persons with type 2 diabetes were randomly assigned to 1 of 4 groups: aerobic training, resistance training, combined aerobic and resistance training, or a control group that reverted to prestudy exercise levels. Participants and trainers could not feasibly be blinded to group assignment after randomization, but the main study outcomes were measured by blinded technologists using objective methods. The study was approved by the Ottawa Hospital Research Ethics Board, and all participants gave informed consent. Setting The exercise intervention took place at 8 community-based exercise facilities in the OttawaGatineau, Canada, region. Exercise was supervised by personal trainers. Participants Previously inactive patients with type 2 diabetes who were 39 to 70 years of age were recruited through advertising, physicians, and word of mouth. Inclusion criteria included type 2 diabetes (as defined by the American Diabetes Association [8]) for more than 6 months and a baseline hemoglobin A1c value of 6.6% to 9.9% (normal range, 4.0% to 6.0%). Exclusion criteria were current insulin therapy; participation in exercise 2 or more times weekly for 20 minutes or longer per session or in any resistance training during the previous 6 months; changes during the previous 2 months in oral hypoglycemic, antihypertensive, or lipid-lowering agents or body weight (5%); serum creatinine level of 200 mol/L or greater (2.26 mg/dL); proteinuria greater than 1 g/d; blood pressure greater than 160/95 mm Hg; restrictions in physical activity because of disease; or presence of other medical conditions that made participation inadvisable. After initial screening by telephone, requisitions for hemoglobin A1c testing were mailed to potentially eligible individuals. Those with a screening hemoglobin A1c value of 6.6% to 9.9% were invited for in-person assessment, where informed consent was obtained, followed by a history and physical examination. Participants returned on a separate day for maximal exercise stress testing with electrocardiographic monitoring by using a ramp protocol on a treadmill. Persons with abnormalities on this test were allowed to proceed in the trial only if cleared by a cardiologist. Run-in Phase Before randomization, all participants entered a 4-week run-in phase to assess adherence. Participants performed 15 to 20 minutes of aerobic exercise and 1 or 2 sets of 8 resistance exercises, at moderate intensity and with supervision. Only persons who attended 10 or more of the scheduled 12 run-in sessions were eligible for randomization. Randomization Participants were randomly allocated in equal numbers to the aerobic training, resistance training, combined exercise training, and control groups and were stratified by sex and age (39 to 54 years or 55 to 70 years). Central randomization was used, with allocation concealment before randomization, and block sizes varied randomly between 4 and 8. To permit blinding of the research coordinator, the personal trainer rather than the research coordinator handled the randomization visit. Intervention All exercise group participants were provided with a 6-month membership at the exercise facility; the membership fees were covered by study funding to remove economic barriers to participation. Individual exercise supervision was provided weekly for the first 4 weeks after randomization and biweekly thereafter. Attendance was verified through direct observation, exercise logs, and electronic scanning of membership cards. Exercise group participants exercised 3 times weekly, and training progressed gradually in duration and intensity. The aerobic training group exercised on treadmills or bicycle ergometers. Heart rate monitors (Polar Electro Oy, Kempele, Finland) were used to adjust workload to achieve the target heart rate. Participants progressed from 15 to 20 minutes per session at 60% of the maximum heart rate to 45 minutes per session at 75% of the maximum heart rate, as determined by using a maximal treadmill exercise test. The resistance training group performed 7 different exercises on weight machines each session, progressing to 2 to 3 sets of each exercise at the maximum weight that could be lifted 7 to 9 times. The combined exercise training group did the full aerobic training program plus the full resistance training program to ensure an adequate dose of each type of exercise. The frequency of direct supervision by trainers was the same in all exercise groups. Control participants were asked to revert to prestudy activity levels. The Appendix shows details of the exercise training programs. Background physical activity was assessed in all participants by using pedometers (Yamax DIGIWALKER SW-700, Yamax Corporation, Tokyo, Japan). Participants wore pedometers for 1 full week at baseline, week 13, and week 26, except when showering or sleeping. Background activity was defined as the mean daily total step count for the days on which the pedometer was worn, excluding steps during scheduled exercise sessions. We recommended a diet to all participants that would not cause weight loss to minimize dietary variability among groups. Dietary counseling was based on Canadian Diabetes Association guidelines (9). The dietitian interviewed each participant at baseline, 3 months, and 6 months and reviewed a 3-day food diary. Food diaries were coded by using Nutribase software, version 4 (Cybersoft, Phoenix, Arizona). Prescribed energy intake was 90% or more of estimated weight maintenance requirements (10). We took steps to minimize dietary and medication co-intervention. Letters were sent to participants' physicians asking that therapy with antihypertensive, lipid-altering, or glucose-lowering medications not be initiated or altered during the 6-month intervention unless it was medically necessary. When medication changes were deemed necessary, we asked physicians and participants to inform us of these. If the hemoglobin A1c value increased at 3 months to 10.5% or greater, we increased oral hypoglycemic therapy in a stepwise manner. If frequent hypoglycemia occurred, we decreased oral hypoglycemic medication in a stepwise manner. We did not initiate changes in antihypertensive or lipid-lowering agents between enrollment and 6 months. Control participants had the same dietary intervention and spent the same time with the research coordinator and dietitian as did participants in the exercise groups. Control participants and exercise group participants who completed 70% or more of the prescribed sessions received free YMCA memberships for 6 months after the end of the intervention. No other compensation was provided to the participants. Control participants were offered the exercise program of their choice after we obtained measurements at 6 months. This minimized the likelihood of contamination during the intervention and provided an incentive to participate in the study. After the end of the intervention, participants who exercised previously received exercise supervision only at their request, and restrictions on exercise method or medication changes were lifted for all groups. Outcomes and Measurements The primary outcome was the absolute change in hemoglobin A1c value between baseline and the end of the 6-month supervised exercise period. Secondary outcomes were plasma lipid values, blo