Effects of Aerobic Training, Resistance Training, or Both on GlycemicControl in Type 2 DiabetesA Randomized TrialRonald J. Sigal, MD, MPH; Glen P. Kenny, PhD; Normand G. Boule´, PhD; George A. Wells, PhD; Denis Prud’homme, MD, MSc;Michelle Fortier, PhD; Robert D. Reid, PhD, MBA; Heather Tulloch, MSc; Douglas Coyle, PhD; Penny Phillips, MA; Alison Jennings, MA;and … Continue reading “effects of aerobic training alone | My Assignment Tutor”
Effects of Aerobic Training, Resistance Training, or Both on GlycemicControl in Type 2 DiabetesA Randomized TrialRonald J. Sigal, MD, MPH; Glen P. Kenny, PhD; Normand G. Boule´, PhD; George A. Wells, PhD; Denis Prud’homme, MD, MSc;Michelle Fortier, PhD; Robert D. Reid, PhD, MBA; Heather Tulloch, MSc; Douglas Coyle, PhD; Penny Phillips, MA; Alison Jennings, MA;and James Jaffey, MScBackground: Previous trials have evaluated the effects of aerobictraining alone and of resistance training alone on glycemic controlin type 2 diabetes, as assessed by hemoglobin A1c values. However,none could assess incremental effects of combined aerobic andresistance training compared with either type of exercise alone.Objective: To determine the effects of aerobic training alone, resistance training alone, and combined exercise training on hemoglobin A1c values in patients with type 2 diabetes.Design: Randomized, controlled trial.Setting: 8 community-based facilities.Patients: 251 adults age 39 to 70 years with type 2 diabetes. Anegative result on a stress test or clearance by a cardiologist, andadherence to exercise during a 4-week run-in period, were requiredbefore randomization.Interventions: Aerobic training, resistance training, or both types ofexercise (combined exercise training). A sedentary control groupwas included. Exercise training was performed 3 times weekly for22 weeks (weeks 5 to 26 of the study).Measurements: The primary outcome was the change in hemoglobin A1c value at 6 months. Secondary outcomes were changes inbody composition, plasma lipid values, and blood pressure.Results: The absolute change in the hemoglobin A1c value in thecombined exercise training group compared with the control groupwas 0.51 percentage point (95% CI, 0.87 to 0.14) in theaerobic training group and 0.38 percentage point (CI, 0.72 to0.22) in the resistance training group. Combined exercise trainingresulted in an additional change in the hemoglobin A1c value of0.46 percentage point (CI, 0.83 to 0.09) compared withaerobic training alone and 0.59 percentage point (CI, 0.95 to0.23) compared with resistance training alone. Changes in bloodpressure and lipid values did not statistically significantly differamong groups. Adverse events were more common in the exercisegroups.Limitations: The generalizability of the results to patients who areless adherent to exercise programs is uncertain. The participantswere not blinded, and the total duration of exercise was greater inthe combined exercise training group than in the aerobic andresistance training groups.Conclusion: Either aerobic or resistance training alone improvesglycemic control in type 2 diabetes, but the improvements aregreatest with combined aerobic and resistance training.Ann Intern Med. 2007;147:357-369. www.annals.orgFor author affiliations, see end of text.ClinicalTrials.gov registration number: NCT00195884.P2 diabetes mellitus. Systematic reviews (1–4) found hysical activity is important in the management of typethat 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 glucoseconcentration over the previous 2 to 3 months. A 1%absolute decrease in the hemoglobin A1c value is associatedwith 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 andresistance training with aerobic training alone found nodifferences 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 thepower 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 typesof exercise (combined exercise training) versus aerobic orresistance training alone, on glycemic control and otherrisk factors for cardiovascular disease. We report our resultsfor the primary outcome (change in hemoglobin A1c valuefrom baseline to the end of the intervention) and for thesecondary outcomes of plasma lipid levels, blood pressure,and body composition. We hypothesized that the decreasein hemoglobin A1c value would be greater in the aerobicand resistance training groups than the control group andwould be even greater in the combined exercise traininggroup than the aerobic or resistance training group.See also:PrintEditors’ Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 358Editorial comment. . . . . . . . . . . . . . . . . . . . . . . . . . 423Summary for Patients. . . . . . . . . . . . . . . . . . . . . . . I-16Web-OnlyAppendixAppendix TablesConversion of graphics into slidesAudio summaryAnnals of Internal Medicine Article© 2007 American College of Physicians 357Downloaded from https://annals.org by guest on 02/14/2020METHODSDesignWe conducted a 26-week, single-center, randomized,controlled trial with a parallel-group design. After a 4-weekrun-in phase, previously inactive persons with type 2 diabetes were randomly assigned to 1 of 4 groups: aerobictraining, resistance training, combined aerobic and resistance training, or a control group that reverted to prestudyexercise levels. Participants and trainers could not feasiblybe blinded to group assignment after randomization, butthe main study outcomes were measured by blinded technologists using objective methods. The study was approvedby the Ottawa Hospital Research Ethics Board, and allparticipants gave informed consent.SettingThe exercise intervention took place at 8 communitybased exercise facilities in the Ottawa–Gatineau, Canada,region. Exercise was supervised by personal trainers.ParticipantsPreviously inactive patients with type 2 diabetes whowere 39 to 70 years of age were recruited through advertising, physicians, and word of mouth. Inclusion criteriaincluded 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 insulintherapy; participation in exercise 2 or more times weeklyfor 20 minutes or longer per session or in any resistancetraining during the previous 6 months; changes during theprevious 2 months in oral hypoglycemic, antihypertensive,or lipid-lowering agents or body weight (5%); serumcreatinine level of 200 mol/L or greater (2.26 mg/dL);proteinuria greater than 1 g/d; blood pressure greater than160/95 mm Hg; restrictions in physical activity because ofdisease; or presence of other medical conditions that madeparticipation inadvisable.After initial screening by telephone, requisitions forhemoglobin A1c testing were mailed to potentially eligibleindividuals. Those with a screening hemoglobin A1c valueof 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 aseparate day for maximal exercise stress testing with electrocardiographic monitoring by using a ramp protocol on atreadmill. Persons with abnormalities on this test were allowed to proceed in the trial only if cleared by a cardiologist.Run-in PhaseBefore randomization, all participants entered a4-week run-in phase to assess adherence. Participants performed 15 to 20 minutes of aerobic exercise and 1 or 2 setsof 8 resistance exercises, at moderate intensity and withsupervision. Only persons who attended 10 or more of thescheduled 12 run-in sessions were eligible for randomization.RandomizationParticipants were randomly allocated in equal numbersto the aerobic training, resistance training, combined exercise training, and control groups and were stratified by sexand age (39 to 54 years or 55 to 70 years). Central randomization was used, with allocation concealment beforerandomization, and block sizes varied randomly between 4and 8. To permit blinding of the research coordinator, thepersonal trainer rather than the research coordinator handled the randomization visit.InterventionAll exercise group participants were provided with a6-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 afterrandomization and biweekly thereafter. Attendance wasverified through direct observation, exercise logs, and electronic scanning of membership cards. Exercise group participants exercised 3 times weekly, and training progressedgradually in duration and intensity. The aerobic traininggroup exercised on treadmills or bicycle ergometers. Heartrate monitors (Polar Electro Oy, Kempele, Finland) wereused to adjust workload to achieve the target heart rate.Participants progressed from 15 to 20 minutes per sessionat 60% of the maximum heart rate to 45 minutes persession at 75% of the maximum heart rate, as determinedby using a maximal treadmill exercise test. The resistancetraining group performed 7 different exercises on weightmachines each session, progressing to 2 to 3 sets of eachexercise at the maximum weight that could be lifted 7 to 9times. The combined exercise training group did the fullaerobic training program plus the full resistance trainingprogram to ensure an adequate dose of each type of exercise. The frequency of direct supervision by trainers wasContextThe benefits of exercise in improving glycemic control inpatients with type 2 diabetes are well documented. Previous studies have examined aerobic or resistance exercisealone but not in combination.ContributionThis randomized, controlled trial showed better reductionin hemoglobin A1c values in patients who followed a combined aerobic exercise and resistance training program 3times weekly than in patients who followed a program ofeither exercise type alone.CautionPatients 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 conclusionsabout whether the benefits were due to longer exerciseduration or to the combined exercise training.—The EditorsArticle Effects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes358 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 www.annals.orgDownloaded from https://annals.org by guest on 02/14/2020the same in all exercise groups. Control participants wereasked to revert to prestudy activity levels. The Appendix(available at www.annals.org) shows details of the exercisetraining programs.Background physical activity was assessed in all participants by using pedometers (Yamax DIGIWALKER SW-700, Yamax Corporation, Tokyo, Japan). Participants worepedometers for 1 full week at baseline, week 13, and week26, except when showering or sleeping. Background activity was defined as the mean daily total step count for thedays on which the pedometer was worn, excluding stepsduring scheduled exercise sessions.We recommended a diet to all participants that wouldnot cause weight loss to minimize dietary variability amonggroups. Dietary counseling was based on Canadian Diabetes Association guidelines (9). The dietitian interviewedeach participant at baseline, 3 months, and 6 months andreviewed a 3-day food diary. Food diaries were coded byusing Nutribase software, version 4 (Cybersoft, Phoenix,Arizona). Prescribed energy intake was 90% or more ofestimated weight maintenance requirements (10).We took steps to minimize dietary and medicationco-intervention. Letters were sent to participants’ physicians asking that therapy with antihypertensive, lipid-altering, or glucose-lowering medications not be initiated oraltered during the 6-month intervention unless it was medically necessary. When medication changes were deemednecessary, we asked physicians and participants to informus of these. If the hemoglobin A1c value increased at 3months to 10.5% or greater, we increased oral hypoglycemic therapy in a stepwise manner. If frequent hypoglycemia occurred, we decreased oral hypoglycemic medicationin a stepwise manner. We did not initiate changes in antihypertensive or lipid-lowering agents between enrollmentand 6 months.Control participants had the same dietary interventionand spent the same time with the research coordinator anddietitian as did participants in the exercise groups. Controlparticipants and exercise group participants who completed70% or more of the prescribed sessions received freeYMCA memberships for 6 months after the end of theintervention. No other compensation was provided to theparticipants. Control participants were offered the exerciseprogram of their choice after we obtained measurements at6 months. This minimized the likelihood of contaminationduring 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 exercisemethod or medication changes were lifted for all groups.Outcomes and MeasurementsThe primary outcome was the absolute change in hemoglobin A1c value between baseline and the end of the6-month supervised exercise period. Secondary outcomeswere plasma lipid values, blood pressure, and body composition. Hemoglobin A1c was measured by using turbidimetric immunoinhibition, and total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride levelswere measured by using enzymatic methods on a Beckman-Coulter LX20 analyzer (Beckman Instruments, Brea,California). Low-density lipoprotein (LDL) cholesterol levels were calculated by using the Friedewald equation (11).Impedance and reactance were obtained by using a bioelectrical impedance analyzer (101A Analyzer, RJL Systems, Clinton, Michigan), and fat-free mass was calculatedby using the equation of Kyle and colleagues (12). Fat masswas calculated by subtracting fat-free mass from bodyweight. Percentage of body fat was calculated by dividingfat mass by body weight. Blood pressure was measuredafter 10 minutes at rest; the mean of 2 readings obtained 2minutes apart was used in statistical analysis.On separate days at least 48 hours apart, participantsunderwent strength testing and computed tomography(CT). Strength testing involved determination of the maximum weight that could be lifted 8 times while maintaining proper form. The CT protocol included a scout radiograph, a transverse cut at L4 to L5 to measure abdominalvisceral and subcutaneous fat (13, 14), and a mid-thigh cutmidway between the inguinal crease and the proximal border of the patella to assess muscle cross-sectional area (15).The images were downloaded as digital files and analyzedby using Slice-O-Matic software, version 4 (Tomovision,Montre´al, Que´bec, Canada), as described elsewhere (7).All participants were reassessed as described at 3 and 6months (the end of the intervention), except that CT wasperformed only at baseline and 6 months. Participantswere instructed not to exercise for 48 hours or more beforeeach visit.Adverse EventsWe used a standard form to log each adverse event.Participants were questioned on adverse events by the research coordinator at the 3- and 6-month visits and by theexercise specialist if a scheduled exercise session was missed.In addition, adverse event forms were completed if a participant spontaneously reported an adverse event to anyresearch staff.Statistical AnalysisWe calculated that a sample size of 216 persons (54per group) was needed to have 80% power to detect amoderate 0.65-SD difference for each of 4 comparisonstested simultaneously, with an overall value of 0.05: aerobic training versus control, resistance training versus control, combined exercise training versus aerobic training (incremental effect of resistance training beyond that ofaerobic training), and combined exercise training versusresistance training (incremental effect of aerobic trainingbeyond that of resistance training). We exceeded this sample size to allow for withdrawals. Previous studies of theeffect of aerobic training alone (1) and resistance trainingalone (16–18) suggested that results of each type of exerEffects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes Articlewww.annals.org 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 359Downloaded from https://annals.org by guest on 02/14/2020cise would be comparable. Therefore, the study was notpowered to compare aerobic training with resistance training, which would have required a much larger sample.We performed analyses on an intention-to-treat basisand included all randomly allocated persons (includingthose who later withdrew). We used SAS, version 9 (SASInstitute, Cary, North Carolina), for all analyses of continuous variables.For the primary analysis, we used a linear mixedeffects model for repeated measures over time, with hemoglobin A1c as the dependent variable and effects for time,study group, and time-by-group interaction; covariateswere age, sex, body mass index, use of oral hypoglycemicmedication, and specific exercise facility, with an unstructured covariance matrix. Within the mixed model, we estimated 95% CIs and P values for the 4 prespecified intergroup contrasts (combined exercise training versus aerobictraining, combined exercise training versus resistance training, aerobic training versus control, and resistance trainingversus control) for change in hemoglobin A1c value between baseline and 6 months and over time within eachgroup.To test whether changes in the hemoglobin A1c valuediffered according to the baseline hemoglobin A1c value,we reran the model with the addition of a term for hemoglobin A1c values at or above the median and a term for theinteraction between hemoglobin A1c values at or above themedian and time. In a prespecified secondary analysis, werepeated the primary analysis separately for participantswith baseline hemoglobin A1c values at or above the median and for those with values below the median. In asensitivity analysis, we repeated the primary analysis, excluding participants with changes in oral hypoglycemicmedication.For continuous secondary outcomes (anthropometricvariables, body composition, lipid values, blood pressure),we used the same procedure as in the primary analysis.Models for lipid values and blood pressure used the samecovariates as the hemoglobin A1c models. Models for bodycomposition used the same covariates except for body massindex. For blood pressure, we also performed a sensitivityanalysis that excluded participants who had changes totheir antihypertensive medication regimen, and for lipidvalues, we performed a sensitivity analysis that excludedparticipants who had changes to their lipid medication regimen. For all linear mixed-model analyses, we examinedthe distributions of residuals and used transformations toachieve normality when necessary.For discrete secondary outcomes, such as starting orincreasing the dose of hypoglycemic medication and discontinuing or decreasing the dose of hypoglycemic medication, we used the Fisher exact test (available at www.graphpad.com/quickcalcs/contingency1.cfm) for the 4prespecified intergroup comparisons. Changes in antihypertensive and lipid-altering drugs were analyzed separately by using the same procedure as for changes in oralhypoglycemic drugs. In a post hoc analysis, we used theFisher exact test to compare the numbers of participantswith adverse events in all exercise groups combined versusthose in the control group.Role of the Funding SourcesThe DARE trial was supported by grants from theCanadian Institutes of Health Research (MCT-44155) andthe Canadian Diabetes Association (The Lillian Hollefriend Grant). The funding sources had no role in design,conduct, or reporting of the study.RESULTSBetween October 1999 and December 2003, 2282people were screened. The Figure shows the flow of participants from recruitment to follow-up. The most common reasons for medical exclusion were musculoskeletalproblems limiting exercise (33%), undiagnosed diabetes(24%), and current insulin therapy (13%). Follow-up forthe final participant was completed in May 2005. Of the258 people who entered the run-in phase, 251 (97.3%)were randomly assigned. Of the 7 people who were notrandomly assigned, 4 had inadequate adherence and 3chose not to proceed because of aggravation of arthritis.Table 1 shows the participants’ baseline characteristics. The groups were similar in age, sex, ethnicity, duration of diabetes, and medication use.Adherence to Exercise TrainingFrom baseline to 26 weeks, the median exercise training attendance was 86% (interquartile range, 74% to 92%)in the combined exercise training group, 80% (interquartile range, 46% to 93%) in the aerobic training group, and85% (interquartile range, 72% to 91%) in the resistancetraining group. Thirty (12%) persons withdrew betweenrandomization and 6 months: 8 (13%) combined exercisetraining participants, 12 (20%) aerobic training participants, 7 (11%) resistance training participants, and 3 (5%)control participants. The 4 persons who withdrew for medical reasons were all in the aerobic training group. Theremaining persons in the exercise groups who withdrewcited a lack of time or loss of interest. Three individualsassigned to the control group withdrew because they weredissatisfied with allocation to this group. Only 1 personassigned to aerobic training reported participating in resistance training, and no one assigned to resistance trainingreported engaging in aerobic activity beyond prestudy levels. Outside of DARE exercise sessions, background physical activity recorded with pedometers did not change materially over time in any group.Glycemic ControlTable 2 shows overall results, and Appendix Table 1(available at www.annals.org) provides details on withingroup changes and subgroup analyses. Adjusted absolutehemoglobin A1c values decreased significantly in the aeroArticle Effects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes360 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 www.annals.orgDownloaded from https://annals.org by guest on 02/14/2020bic training group compared with the control group(change, 0.51 percentage point; P 0.007) and in theresistance training group compared with the control group(change, 0.38 percentage point; P 0.038). In the combined exercise training group, hemoglobin A1c valueschanged by an additional 0.46 percentage point compared with the aerobic training group (P 0.014) and0.59 percentage point compared with the resistancetraining group (P 0.001). Among participants with abaseline hemoglobin A1c value at or above the median of7.5%, decreases in hemoglobin A1c value were greater thanin those with values less than the median (P 0.001 forinteraction of group, time, and hemoglobin A1c value),whereas among participants with baseline hemoglobin A1cvalues less than 7.5%, significant decreases occurred onlyin the combined exercise training group. In a sensitivityanalysis, we excluded persons with any changes in oral hypoglycemic medications, and results were similar to thoseof the overall study sample.Four combined exercise training participants, 5 resistance training participants, 5 aerobic training participants,and 9 control participants had increases in the dose orinitiation of oral hypoglycemic therapy; 4, 5, 6, and 3participants, respectively, had a decrease in dose or discontinuation of therapy; and 2, 0, 1, and 1 participant, respectively, had both increases and decreases in dose. No significant intergroup differences were observed for any of thesechanges (Appendix Table 2, available at www.annals.org).Figure. Study flow diagram.HbA1c hemoglobin A1c.Effects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes Articlewww.annals.org 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 361Downloaded from https://annals.org by guest on 02/14/2020Blood Pressure and Lipid ValuesThe distribution of residuals was found to be positively skewed for HDL cholesterol and triglycerides. Thesevariables were therefore transformed to the logarithm foranalyses, resulting in normal distributions of residuals.Changes in blood pressure; total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride levels; and the totalcholesterol–HDL cholesterol ratio did not statistically significantly differ among groups (Table 2). Six combinedexercise training participants, 10 aerobic training participants, 5 resistance training participants, and 4 control participants had increases in the dose or initiation of oralantihypertensive therapy; 4, 1, 0, and 2 participants, respectively, had a decrease in dose or discontinuation oftherapy; and 1, 1, 0, and 3 participants, respectively, hadboth increases and decreases in dose. Nine combined exercise training participants, 6 aerobic training participants, 4resistance training participants, and 7 control participantshad an increase in dose or initiation of lipid-lowering medication; 4, 1, 0, and 2 participants, respectively, had a decrease in dose or discontinuation of therapy; and 0, 1, 1,and 0 participants, respectively, had both increases anddecreases in dose. These changes were initiated by the participants’ regular physicians or the participants themselves,not by DARE investigators, and did not differ in frequencyamong groups. No statistically significant intergroup differences were observed in any of these changes (AppendixTable 2, available at www.annals.org).Body CompositionTable 3 shows changes in body composition. Changesin the combined exercise training group did not differ fromthose in the aerobic training or resistance training groups.Body weight and body mass index decreased more in theaerobic training group than in the control group (P0.008 and P 0.009, respectively). Waist circumferencedecreased more in the aerobic training and resistance training groups than in the control group (P 0.030 and P0.054, respectively), as did abdominal subcutaneous fat(P 0.035 and P 0.020, respectively). Intergroup differences in change in abdominal visceral fat were not statistically significant. Increases in mid-thigh muscle crosssectional area were significantly greater in the aerobictraining and resistance training groups than in the controlgroup (P 0.003 and P 0.001, respectively).Dietary IntakeAll groups had similar slight decreases in overall caloricintake over time. No statistically significant intergroupdifferences in macronutrient composition were observed(Appendix Table 3, available at www.annals.org).Table 1. Baseline CharacteristicsCharacteristic Combined ExerciseTraining Group(n 64)AerobicTraining Group(n 60)ResistanceTraining Group(n 64)Control Group(n 63) Men/women, n/nMean age (SD), yNon-Hispanic white race/other race, n/nMean duration of diabetes (SD), yMean hemoglobin A1c value (SD), %Medications, n (%)Oral hypoglycemic agents40/2453.5 (7.3)55/95.2 (4.8)7.67 (0.91)39/2153.9 (6.6)59/15.1 (3.5)7.68 (0.85)40/2454.7 (7.5)55/96.1 (4.7)7.71 (0.86)41/2254.8 (7.2)61/25.0 (4.5)7.66 (0.89)TotalMetforminSulfonylureaMeglitinide-Glucosidase inhibitorThiazolidinedione43 (67)36 (56)23 (36)1 (2)1 (2)14 (22)49 (82)42 (70)33 (55)2 (3)1 (2)13 (22)48 (75)41 (64)28 (44)4 (6)2 (3)15 (23)50 (83)43 (68)32 (51)4 (6)1 (2)7 (11)Antihypertensive agentsTotalAngiotensin-converting enzyme inhibitorDiuretic-BlockerAngiotensin-receptor blockerCalcium-channel blockerOtherLipid-lowering agentsTotalStatinFibrateOtherAntidepressantAntiplatelet agentAntiobesity agent35 (55)28 (44)8 (13)2 (3)3 (5)9 (14)1 (2)32 (53)20 (33)9 (15)4 (7)4 (7)6 (10)3 (5)36 (56)28 (44)8 (13)9 (14)3 (5)6 (9)0 (0)35 (56)27 (43)10 (17)6 (10)4 (10)7 (11)3 (5)25 (39)22 (34)7 (11)1 (2)4 (6)17 (27)0 (0)24 (40)17 (28)9 (15)2 (3)11 (18)10 (17)0 (0)26 (41)26 (41)1 (2)0 (0)9 (14)14 (22)1 (2)27 (43)24 (38)6 (10)0 (0)6 (10)15 (24)0 (0) Article Effects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes362 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 www.annals.orgDownloaded from https://annals.org by guest on 02/14/2020Table 2. Changes in Hemoglobin A1c, Blood Pressure, and Lipid Values* VariableMean (SD) ValueDifference in Changefrom Baseline to 6P Value Months (95% CI)Baseline 3 mo 6 moHemoglobin A1c [patients], % [n]† Combined exercise groupAerobic training groupResistance training groupControl group7.46 (1.48) [64]7.41 (1.50) [60]7.48 (1.47) [64]7.44 (1.38) [63]6.99 (1.56) [60]7.00 (1.59) [58]7.35 (1.57) [62]7.33 (1.49) [62]6.56 (1.55) [58]6.98 (1.50) [49]7.18 (1.52) [56]7.51 (1.47) [59]––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––0.51 (0.87 to 0.14)0.38 (0.72 to 0.22)0.46 (0.83 to 0.09)0.59 (0.95 to 0.23)0.0070.0380.0140.001 Systolic blood pressure, mm Hg Combined exercise groupAerobic training groupResistance training groupControl group131 (22)134 (22)136 (22)133 (20)133 (26)131 (26)129 (26)131 (24)129 (23)131 (23)131 (23)129 (21)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––1.0 (3.6 to 5.7)0.9 (5.4 to 3.7)1.3 (3.4 to 6.0)3.2 (1.4 to 7.8)0.660.710.590.168 Diastolic blood pressure, mm Hg Combined exercise groupAerobic training groupResistance training groupControl group79 (13)82 (14)80 (13)80 (12)78 (14)79 (14)78 (14)81 (13)79 (14)79 (14)78 (14)79 (13)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––1.5 (4.7 to 1.7)1.4 (4.6 to 1.7)1.7 (1.5 to 5.0)1.7 (1.5 to 4.9)0.360.370.300.30 HDL cholesterol level‡Combined exercise group mmol/Lmg/dLAerobic training groupmmol/Lmg/dLResistance training groupmmol/Lmg/dLControl groupmmol/Lmg/dLIntergroup comparisonsAerobic training vs. controlmmol/Lmg/dLResistance training vs. controlmmol/Lmg/dLCombined exercise vs. aerobic trainingmmol/Lmg/dLCombined exercise vs. resistance trainingmmol/Lmg/dL1.11 (0.40)42.7 (15.2)1.13 (0.40)43.8 (16.0)1.15 (0.40)44.4 (16.8)––––1.09 (0.39)42.1 (15.5)1.11 (0.39)42.8 (15.5)1.10 (0.39)42.6 (16.3)––––1.11 (0.40)42.7 (15.2)1.11 (0.40)42.9 (15.2)1.11 (0.40)42.8 (16.0)––––1.06 (0.32)41.0 (13.5)1.08 (0.40)41.5 (13.5)1.06 (0.40)41.1 (14.3)––––0.78––––––0.01 (0.06 to 0.08)0.4 (2.2 to 2.9)0.95––––––0.00 (0.07 to 0.06)0.1 (2.6 to 2.4)0.35––––––0.03 (0.04 to 0.10)1.2 (1.4 to 3.8)0.194––––––0.04 (0.02 to 0.11)1.7 (0.8 to 4.2) LDL cholesterol level§Combined exercise group mmol/Lmg/dL3.09 (1.44)119.2 (56.0)3.01 (1.52)116.3 (57.6)2.98 (1.44)115.0 (56.0)–––– Continued on following pageEffects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes Articlewww.annals.org 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 363Downloaded from https://annals.org by guest on 02/14/2020Table 2—Continued VariableMean (SD) ValueDifference in Changefrom Baseline to 6P Value Months (95% CI)Baseline 3 mo 6 moAerobic training group mmol/Lmg/dLResistance training groupmmol/Lmg/dLControl groupmmol/Lmg/dLIntergroup comparisonsAerobic training vs. controlmmol/Lmg/dLResistance training vs. controlmmol/Lmg/dLCombined exercise vs. aerobic trainingmmol/Lmg/dLCombined exercise vs. resistance trainingmmol/Lmg/dL3.24 (1.46)124.9 (56.8)3.13 (1.54)121.0 (58.4)3.08 (1.46)119.0 (56.8)––––3.03 (1.43)117.0 (55.6)2.93 (1.51)113.2 (57.1)3.01 (1.43)116.2 (56.4)––––2.99 (1.34)115.5 (52.8)3.11 (1.42)119.9 (54.3)2.97 (1.34)114.5 (52.8)––––0.33––––––0.13 (0.38 to 0.13)4.9 (14.8 to 4.9)0.97––––––0.00 (0.24 to 0.25)0.2 (9.3 to 9.6)0.74––––––0.04 (0.21 to 0.30)1.6 (8.2 to 11.5)0.47––––––0.09 (0.33 to 0.16)3.4 (12.9 to 6.0) Non–HDL cholesterol levelCombined exercise group mmol/Lmg/dLAerobic training groupmmol/Lmg/dLResistance training groupmmol/Lmg/dLControl groupmmol/Lmg/dLIntergroup comparisonsAerobic training vs. controlmmol/Lmg/dLResistance training vs. controlmmol/Lmg/dLCombined exercise vs. aerobic trainingmmol/Lmg/dLCombined exercise vs. resistance trainingmmol/Lmg/dL3.92 (1.68)151.2 (63.2)3.70 (1.68)143.0 (66.4)3.66 (1.68)141.1 (67.4)––––4.07 (1.70)157.1 (64.3)3.93 (1.70)151.8 (66.6)4.00 (1.78)154.3 (67.4)––––3.97 (1.60)153.1 (63.2)3.85 (1.68)148.7 (65.6)3.85 (1.68)148.6 (65.6)––––3.98 (1.51)153.7 (58.7)4.09 (1.59)157.7 (61.9)3.94 (1.59)151.9 (61.1)––––0.87––––––0.03 (0.34 to 0.29)1.0 (13.3 to 11.2)0.65––––––0.07 (0.38 to 0.24)2.7 (14.6 to 9.1)0.25––––––0.19 (0.51 to 0.13)7.2 (19.5 to 5.1)0.36––––––0.14 (0.44 to 0.17)5.5 (17.5 to 6.4) Triglyceride level‡Combined exercise group mmol/Lmg/dLAerobic training groupmmol/Lmg/dLResistance training groupmmol/Lmg/dLControl groupmmol/Lmg/dL1.61 (1.36)142.4 (124.0)1.36 (1.20)120.4 (104.8)1.35 (1.20)119.2 (136.3)––––1.78 (1.55)157.2 (137.9)1.64 (1.47)145.0 (127.0)1.69 (1.55)149.7 (136.3)––––1.83 (1.52)161.5 (139.2)1.79 (1.52)158.7 (136.8)1.62 (1.44)143.6 (128.0)––––1.88 (1.51)166.5 (134.1)1.82 (1.43)161.0 (129.4)1.89 (1.59)167.0 (138.9)–––– Article Effects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes364 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 www.annals.orgDownloaded from https://annals.org by guest on 02/14/2020Adverse EventsTable 4 shows details of adverse events. Four individuals, all in the aerobic training group, withdrew because ofadverse events: worsening osteoarthritis (2 persons), angina(1 person), and newly diagnosed spinal stenosis (1 person).Overall, adverse events occurred in 71 of the 188 (38%)exercise group participants and 10 of the 63 (14%) controlparticipants (P 0.001, Fisher exact test for control groupversus exercise groups). Musculoskeletal injury or discomfort requiring modification of the exercise program or temporary restriction of activity occurred in 49 of the 188(26%) exercise group participants and 9 of the 63 (14%)control participants (P 0.059 for control group versusexercise groups). No episode of hypoglycemia was severeenough to require assistance. Two combined exercise training participants, 4 aerobic training participants, 4 resistance training participants, and 1 control participant reportedmild hypoglycemia. Doses of hypoglycemic medications weresubsequently reduced in 9 of these 12 participants, and dietarycarbohydrate intake was adjusted in the remaining 3 (1 resistance training participant and 2 aerobic training participants).DISCUSSIONOur primary findings were that aerobic training andresistance training each improved glycemic control, andthat the combination of these 2 forms of exercise was superior to either type of exercise alone. Exercise-inducedimprovements in glycemic control were greater among persons with higher baseline hemoglobin A1c values. Amongpersons with lower baseline hemoglobin A1c values, onlycombined aerobic and resistance training improved values;aerobic or resistance training alone did not. Therefore, individuals with good glycemic control who wish to furtherimprove their hemoglobin A1c through lifestyle measureswould be well advised to do both aerobic and resistanceexercise. If glycemic control is poor, either aerobic or resistance training alone would also improve the hemoglobinA1c value, but the combination of these forms of exercisewould be better.We chose to have the combined exercise traininggroup perform the full aerobic training program plus thefull resistance training program, rather than keeping totalexercise time constant across groups by abbreviating theaerobic and resistance training programs in this group.This ensured that participants received an adequate dose ofeach type of exercise, and the programs for each type ofexercise were similar to those of proven hemoglobin A1c–lowering efficacy in previous trials. Our trial was not designed to study effects of exercise volume or duration perse, and the superior effect of combined aerobic and resistance training may reflect the greater amount of exerciseTable 2—Continued VariableMean (SD) ValueDifference in Changefrom Baseline to 6P Value Months (95% CI)Baseline 3 mo 6 moIntergroup comparisons Aerobic training vs. controlmmol/Lmg/dLResistance training vs. controlmmol/Lmg/dLCombined exercise vs. aerobic trainingmmol/Lmg/dLCombined exercise vs. resistance trainingmmol/Lmg/dL0.48––––––0.09 (0.35 to 0.16)8.1 (30.6 to 14.3)0.089––––––0.21 (0.46 to 0.03)18.9 (40.6 to 2.9)0.078––––––0.23 (0.48 to 0.03)20.3 (42.9 to 2.3)0.39––––––0.11 (0.36 to 0.14)9.6 (31.5 to 12.4) Total cholesterol–HDL cholesterol ratio Combined exercise groupAerobic training groupResistance training groupControl group4.67 (2.08)4.78 (2.09)4.73 (2.08)4.82 (1.90)4.37 (2.08)4.63 (2.09)4.62 (2.08)4.85 (1.90)4.28 (2.24)4.79 (2.25)4.64 (2.16)4.86 (2.06)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––0.02 (0.46 to 0.42)0.13 (0.56 to 0.29)0.40 (0.84 to 0.04)0.29 (0.72 to 0.14)0.920.540.0760.18 * Results are estimated means from linear mixed-effects models, adjusted for age, sex, exercise training site, body mass index, and use or nonuse of oral hypoglycemicmedication. Unless otherwise indicated, the sample for analysis was 64 combined exercise training participants, 60 aerobic training participants, 64 resistance trainingparticipants, and 63 control participants. HDL high-density lipoprotein; LDL low-density lipoprotein.† Values in brackets are numbers of patients with complete data.‡ Values were transformed to the logarithm for analysis and then exponentiated.§ The sample for analysis was 64 combined exercise training participants, 59 aerobic training participants, 63 resistance training participants, and 62 control participants.Plasma triglyceride levels were too high in 3 participants to use the Friedewald equation to calculate the LDL cholesterol level.Effects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes Articlewww.annals.org 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 365Downloaded from https://annals.org by guest on 02/14/2020Table 3. Changes in Body Composition* VariableMean Value (SD)Difference in Changefrom Baseline to 6P Value Months (95% CI)Baseline 3 mo 6 moBody weight, kg Combined exercise groupAerobic training groupResistance training groupControl group101.9 (30.4)103.5 (31.0)99.1 (30.4)101.3 (28.6)100.2 (30.4)101.8 (30.2)98.1 (30.4)100.5 (27.8)99.3 (30.4)100.9 (30.2)98.0 (30.4)101.0 (27.8)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––2.2 (3.9 to 0.6)0.7 (2.4 to 0.9)0.0 (1.6 to 1.7)1.5 (3.1 to 0.1)0.0080.360.980.075 Body mass index, kg/m2 Combined exercise groupAerobic training groupResistance training groupControl group35.0 (9.6)35.6 (10.1)34.1 (9.6)35.0 (9.5)34.5 (9.6)35.1 (10.1)33.8 (9.6)34.8 (8.7)34.2 (9.6)34.8 (10.1)33.7 (9.6)34.9 (8.7)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––0.74 (1.29 to 0.18)0.26 (0.80 to 0.28)0.03 (0.58 to 0.53)0.50 (1.05 to 0.04)0.0090.350.930.069 Waist circumference, cm Combined exercise groupAerobic training groupResistance training groupControl group112 (24)113 (23)110 (24)112 (24)109 (24)110 (23)108 (24)110 (24108 (24)110 (23)107 (24)111 (24)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––2.1 (4.1 to 0.2)1.8 (3.7 to 0.03)0.1 (1.8 to 2.0)0.2 (2.1 to 1.7)0.0300.0540.910.85 Lean body mass, kg† Combined exercise groupAerobic training groupResistance training groupControl group63.9 (13.6)64.0 (13.9)62.3 (13.6)63.0 (12.7)63.5 (13.6)63.1 (13.9)61.9 (13.6)62.5 (12.7)63.2 (13.6)63.0 (13.9)62.5 (13.6)62.5 (12.7)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––0.47 (1.96 to 1.03)0.75 (0.70 to 2.20)0.31 (1.20 to 1.81)0.91 (2.37 to 0.55)0.540.310.690.22 Fat mass, kg† Combined exercise groupAerobic training groupResistance training groupControl group37.6 (19.2)39.2 (19.4)36.5 (19.2)38.0 (17.5)36.3 (19.2)38.3 (19.4)35.9 (18.4)37.7 (17.5)35.7 (19.2)37.6 (19.4)35.2 (19.2)38.2 (17.5)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––1.84 (3.63 to 0.05)1.54 (3.29 to 0.20)0.23 (2.03 to 1.57)0.53 (2.28 to 1.23)0.0440.0820.800.56 Body fat, %† Combined exercise groupAerobic training groupResistance training groupControl group36.0 (9.6)37.0 (9.3)35.9 (9.6)36.6 (8.7)35.2 (9.6)36.8 (9.3)35.8 (9.6)36.7 (8.7)35.0 (9.6)36.3 (9.3)35.0 (9.6)36.9 (9.5)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––1.0 (2.6 to 0.6)1.2 (2.7 to 0.4)0.4 (2.0 to 1.2)0.1 (1.7 to 1.4)0.230.1300.660.87 Article Effects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes366 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 www.annals.orgDownloaded from https://annals.org by guest on 02/14/2020performed by the combined exercise training group. However, because the physiologic effects of aerobic training(19) differ from those of resistance training (20, 21), wecannot assume that our results reflect only additional exercise time. Aerobic training involves continuous activity ofmultiple large muscle groups, whereas resistance traininginvolves isolated, brief activity of single muscle groups. Because of the need to rest between sets due to anaerobicmetabolism in resistance training, less than half the time ofeach resistance exercise session involves active muscle contraction, whereas aerobic exercise is continuous. If ourfindings simply reflected duration of active exercise, wewould expect that the effect of resistance training on hemoglobin A1c would be less than half that of aerobic training, and that the effects of combined exercise trainingwould be less than 1.5 times that of aerobic training. Instead, the effects of aerobic training and resistance trainingon hemoglobin A1c were approximately equal, and those ofcombined exercise training were twice those of aerobic exercise. Even if we assumed that our findings were solely aneffect of greater exercise duration in the combined exercisetraining group, the combined aerobic and resistance program is likely to be more sustainable, because many peoplewould find doing 90 minutes of only 1 type of exercisemonotonous. The effects of aerobic and resistance exerciseon fitness are complementary: Aerobic exercise increasescardiorespiratory fitness, whereas resistance training increases muscle strength and endurance.The effect of resistance training on hemoglobin A1cvalues that we observed was less than that in trials by Dunstan and associates (17) and Castaneda and colleagues (16).There are several possible reasons for this discrepancy. Ourparticipants were younger on average than participants inthose 2 trials. Older persons may benefit more from resisTable 3—Continued VariableMean Value (SD)Difference in Changefrom Baseline to 6P Value Months (95% CI)Baseline 3 mo 6 moAbdominal subcutaneous fat, cm2‡§ Combined exercise groupAerobic training groupResistance training groupControl group416 (230)448 (230)412 (227)420 (209)NDNDNDND389 (230)431 (230)394 (227)416 (209)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––13.5 (25.8 to 1.0)14.3 (26.3 to 2.2)9.5 (21.9 to 2.9)8.6 (20.6 to 3.4)0.0350.0200.1330.160 Abdominal visceral fat, cm2‡§ Combined exercise groupAerobic training groupResistance training groupControl group246 (159)257 (161)228 (156)252 (147)NDNDNDND224 (159)244 (161)218 (156)250 (147)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––11.4 (27.2 to 4.4)8.0 (23.3 to 7.3)8.6 (24.4 to 7.1)12.0 (27.3 to 3.3)0.1570.300.280.124 Mid-thigh muscle cross-sectional area, cm2‡ Combined exercise groupAerobic training groupResistance training groupControl group309 (71)309 (67)302 (69)314 (62)NDNDNDND317 (71)314 (67)308 (69)311 (62)––––––––Intergroup comparisonsAerobic training vs. controlResistance training vs. controlCombined exercise vs. aerobic trainingCombined exercise vs. resistance training––––––––––––7.2 (2.5 to 11.8)8.0 (3.5 to 12.5)3.3 (1.4 to 7.9)2.4 (2.1 to 6.9)0.0030.0010.1680.30 * Results are estimated means from linear mixed-effects models, adjusted for age, sex, exercise training site, and use or nonuse of oral hypoglycemic medication. Unlessotherwise indicated, the sample for analysis was 64 combined exercise training participants, 60 aerobic training participants, 64 resistance training participants, and 63 controlparticipants. ND not done.† Estimated from bioelectrical impedance analysis.‡ Derived by using computed tomography. Computed tomography was performed only at baseline and 6 months.§ The sample for analysis included 63 combined exercise training participants, 59 aerobic training participants, 61 resistance training participants, and 60 control participants.Computed tomography could not be performed in the remaining individuals because they were too large for the scanner.The sample for analysis included 62 combined exercise training participants, 56 aerobic training participants, 59 resistance training participants, and 60 control participants.Computed tomography could not be performed in the remaining individuals because they were too large for the scanner.Effects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes Articlewww.annals.org 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 367Downloaded from https://annals.org by guest on 02/14/2020tance training than do younger persons, because often theyhave lost more muscle mass through disuse (22, 23). Meanhemoglobin A1c values at the start of the other 2 studieswere higher than those in the DARE trial, and we foundgreater improvements in participants with higher baselinehemoglobin A1c values. Dunstan and associates (17) didnot perform an intention-to-treat analysis, which wouldbias toward overestimation of intervention effectiveness.None of our exercise programs had a significant effecton blood pressure compared with the control group, andthe effects of exercise training on plasma lipid levels werelikewise modest. A recent meta-analysis also did not findsignificant exercise-induced changes in these variables (4).To achieve greater changes, higher volumes or intensities ofexercise might be necessary (24).The number of adverse events was larger than we expected and than other investigators have reported, possiblybecause we made a more systematic effort to seek out anddocument such events. The fact that exercise group participants were more frequently questioned about adverseevents may have contributed to the higher number of adverse events reported in these groups compared with thecontrol group. No exercise-induced event led to lastingdisability, no severe hypoglycemic episodes occurred, asubstantial proportion of control participants had adverseevents, and the risk for adverse events was no greater in thecombined exercise training or resistance training groupthan in the aerobic exercise group.Our study participants were probably more adherentto exercise and healthier on average than the general population with type 2 diabetes. Our findings cannot be generalized to patients who cannot or do not wish to undertake exercise programs, just as findings of medication trialscannot be generalized to people who do not wish to takemedications or are intolerant of them. However, the number of individuals participating in our trial far exceeded thenumbers recruited locally for any pharmaceutical trial, indicating that there is considerable interest in lifestyle interventions. We excluded patients who were receiving insulinor who had advanced diabetes complications; therefore,our findings cannot necessarily be generalized to such patients. Moreover, our findings cannot necessarily be generalized to unsupervised exercise programs. The monthlycost of our intervention (exercise facility membership feeplus trainer time) averaged $130 (Canadian) per participant in the aerobic or resistance training groups and $197in the combined exercise training group. These costs woulddecrease over time as the frequency of sessions with a personal trainer decreased.In summary, aerobic training and resistance trainingalone each led to improvements in glycemic control, andcombined aerobic and resistance training had effects thatwere greater than those of either method alone. These effects were more powerful among individuals with poor glycemic control at baseline. The combined aerobic and resistance training program was not associated with reducedTable 4. Adverse Events*Adverse Event Combined ExerciseTraining Group(n 64)AerobicTraining Group(n 60)ResistanceTraining Group(n 64)Control Group(n 63)† Serious adverse events‡HospitalizationsAny injury or musculoskeletal discomfortInjury requiring modification of exercise program or restriction of activityWithdrawal for medical reasonsAll participants with an adverse event0 (0)0 (0)17 (27)15 (23)1 (2)22 (34)4 (7)2 (3)18 (30)16 (27)4 (7)24 (40)0 (0)0 (0)21 (33)18 (28)0 (0)25 (39)0 (0)0 (0)9 (14)9 (14)0 (0)10 (16)Physical adverse eventsShoulder painAggravation of preexisting arthritisTendonitis/epicondylitis/fasciitisBack painShin splintsHeel spursTorn ligament or tendonPinched nerve (sciatic, femoral, or cervical)Musculoskeletal injury due to accident while exercising (dropped weight)Musculoskeletal injury due to accident outside of exercise programOther musculoskeletal discomfort6 (9)0 (0)2 (3)2 (3)1 (2)0 (0)1 (2)0 (0)0 (0)5 (8)3 (5)2 (3)2 (3)3 (5)3 (5)1 (2)2 (3)0 (0)2 (3)0 (0)2 (3)4 (7)7 (11)0 (0)4 (6)2 (3)0 (0)0 (0)1 (2)2 (3)2 (3)1 (2)4 (6)2 (3)0 (0)0 (0)0 (0)0 (0)0 (0)0 (0)2 (3)0 (0)0 (0)5 (8)Medical adverse eventsHypoglycemiaOther medical events§2 (3)0 (0)4 (7)4 (7)4 (6)0 (0)1 (2)0 (0) * Data are the number (percentage) of participants. Percentages are rounded to the nearest 1%. Some individuals had more than 1 type of adverse event—for example, backpain and shoulder pain.† Injuries in the control group were not related to the study exercise program.‡ Serious adverse events (hospitalization or lasting disability) were 2 hospitalizations (1 for elective hysterectomy and 1 for elective hernia repair), 1 case of newly diagnosedspinal stenosis, and 1 case of worsening angina.§ Includes 1 case each of spinal stenosis, elective hysterectomy, temporomandibular joint pain, and inguinal hernia.Article Effects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes368 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 www.annals.orgDownloaded from https://annals.org by guest on 02/14/2020adherence compared with the programs featuring just 1type of exercise, and the number of adverse events was nogreater in the combined exercise training group than in theaerobic or resistance training groups alone. Therefore, persons with type 2 diabetes who wish to improve their metabolic control through physical activity should be encouraged to perform both aerobic and resistance training.From the University of Ottawa, Clinical Epidemiology Program, OttawaHealth Research Institute, and Prevention and Rehabilitation Centre,University of Ottawa Heart Institute, Ottawa, Ontario, Canada, andUniversity of Calgary, Calgary, Alberta, Canada.Acknowledgments: The authors thank the DARE study participants;Diana Pepin, Kim Fetch, Rikst Attema, Katherine Dittmann, KelleyPhillips, Paul Healey, Karen Holland, Jane Murrin, Natalie McInnis,Jason Fetch, and Tina Leech, students in the School of Human Kinetics,University of Ottawa; and the Ottawa-Carleton Regional YMCA/YWCAand Nautilus Plus of Gatineau, Que´bec, Canada, for their contributionsto study coordination, exercise training, and evaluation of study participants.Grant Support: The DARE trial was supported by grants from the Canadian Institutes of Health Research (grant MCT-44155) and the Canadian Diabetes Association (The Lillian Hollefriend Grant). Dr. Sigalwas supported by a New Investigator Award from the Canadian Institutes of Health Research and the Ottawa Health Research Institute Lifestyle Research Chair. Dr. Kenny was supported by a Career ScientistAward from the Ontario Ministry of Health and Long Term Care. Dr.Boule´ was supported by a Postgraduate Scholarship from the NationalSciences and Engineering Research Council of Canada. Dr. Reid wassupported by a New Investigator Award from the Heart and StrokeFoundation of Canada. Ms. Tulloch was supported by a Doctoral Research Award from the Social Sciences and Humanities Research Councilof Canada. Ms. Jennings was supported by an Ontario Graduate Scholarship.Potential Financial Conflicts of Interest: None disclosed.Requests for Single Reprints: Ronald J. Sigal, MD, MPH, Universityof Calgary, 7th Floor, North Tower, Foothills Medical Center, 1403 29Street NW, Calgary, Alberta T2N 2T9, Canada; e-mail, rsigal@ucalgary.ca.Current author addresses and author contributions are available at www.annals.org.References1. Boule´ NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise onglycemic control and body mass in type 2 diabetes mellitus: a meta-analysis ofcontrolled clinical trials. JAMA. 2001;286:1218-27. [PMID: 11559268]2. Eves ND, Plotnikoff RC. Resistance training and type 2 diabetes: Considerations for implementation at the population level. Diabetes Care. 2006;29:1933-41. [PMID: 16873809]3. Snowling NJ, Hopkins WG. Effects of different modes of exercise training onglucose control and risk factors for complications in type 2 diabetic patients: ameta-analysis. Diabetes Care. 2006;29:2518-27. [PMID: 17065697]4. Thomas DE, Elliott EJ, Naughton GA. Exercise for type 2 diabetes mellitus.Cochrane Database Syst Rev. 2006;3:CD002968. 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[PMID: 12421890}Effects of Aerobic and Resistance Training on Glycemic Control in Type 2 Diabetes Articlewww.annals.org 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 369Downloaded from https://annals.org by guest on 02/14/2020Current Author Addresses: Dr. Sigal: University of Calgary, 7th Floor,North Tower, Foothills Medical Center, 1403 29 Street NW, Calgary,Alberta T2N 2T9, Canada.Dr. Kenny: University of Ottawa, Laboratory of Human Bioenergeticsand Environmental Physiology, Montpetit Hall, 125 University Avenue,Ottawa, Ontario K1N 6N5, Canada.Dr. Boule´: Faculty of Physical Education and Recreation, P420, VanVliet Centre, Edmonton, Alberta T6G 2H9, Canada.Dr. Wells: University of Ottawa Heart Institute, 40 Ruskin Street, RoomH1-1, Ottawa, Ontario K1Y 4W7, Canada.Dr. Prud’homme: Faculty of Health Sciences, University of Ottawa, 451Smyth Road, Ottawa, Ontario K1H 8M5, Canada.Dr. Fortier: School of Human Kinetics, University of Ottawa, MontpetitHall, 125 University Avenue, Ottawa, Ontario K1N 6N5, Canada.Dr. Reid and Ms. Tulloch: Prevention and Rehabilitation Centre, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, OntarioK1Y 4W7, Canada.Dr. Coyle: Faculty of Health Sciences, RGN 323, 451 Smyth Road,Ottawa, Ontario K1H 8M5, Canada.Ms. Phillips: Clinical Epidemiology Program, Ottawa Health ResearchInstitute, 1967 Riverside Drive, 4th Floor (Diabetes Research), Ottawa,Ontario K1H 7W9, Canada.Ms. Jennings and Mr. Jaffey: Clinical Epidemiology Program, OttawaHealth Research Institute, 1053 Carling Avenue, Ottawa, Ontario K1Y4E9, Canada.Author Contributions: Conception and design: R.J. Sigal, G.P. Kenny,N.G. Boule´, G.A. Wells, Denis Prud’homme, M. Fortier, R.D. Reid, D.Coyle.Analysis and interpretation of the data: R.J. Sigal, G.P. Kenny, N.G.Boule´, G.A. Wells, Denis Prud’homme, M. Fortier, R.D. Reid, H. Tulloch, D. Coyle, J. Jaffey.Drafting of the article: R.J. Sigal, G.P. Kenny.Critical revision of the article for important intellectual content: R.J.Sigal, G.P. Kenny, N.G. Boule´, G.A. Wells, Denis Prud’homme, M.Fortier, R.D. Reid, H. Tulloch, D. Coyle, A. Jennings.Final approval of the article: R.J. Sigal, G.P. Kenny, N.G. Boule´, DenisPrud’homme, M. Fortier, H. Tulloch, D. Coyle.Provision of study materials or patients: R.J. Sigal, G.P. Kenny, R.D.Reid.Statistical expertise: G.A. Wells, J. Jaffey.Obtaining of funding: R.J. Sigal, G.P. Kenny, G.A. Wells, DenisPrud’homme, M. Fortier., R.D. Reid, D. CoyleAdministrative, technical, or logistic support: G.P. Kenny, P. Phillips, A.Jennings.P. Phillips, A. Jennings.APPENDIX: THE DARE TRIAL EXERCISE INTERVENTIONPROGRAMSAn exercise specialist was present for a minimum of 3 scheduled sessions weekly at each site and supervised all exercise programs. After randomization, the exercise specialist met each participant individually at least weekly for 4 weeks, every 2 weeks forthe subsequent 2 months, and monthly for the remainder of theprogram to ensure appropriate progression through the program.If a participant missed a scheduled session, the exercise specialistcontacted him or her to ascertain what had happened andwhether any specific problems could be addressed. After the initial 2 weeks of the postrandomization period (weeks 5 to 6 of thestudy), participants were free to attend at the times that weremost convenient for them, but they were required to come atleast once weekly during hours when the exercise specialist waspresent.The exercise specialist monitored attendance and completion of exercise logs. Attendance was verified by the exercise logsand by electronic scanning of the membership card each time aparticipant came to the gym.Every exercise session began with a 5- to 10-minutewarm-up consisting of very light exercises, which was designed toallow a gradual warming of the muscles before engaging in vigorous exercise, and ended with a cool-down (5 to 10 minutes oflight exercises and stretching).Aerobic TrainingAerobic training was divided into a prerandomization run-inphase (weeks 1 to 4) and a postrandomization intervention phase(weeks 5 to 26). The aim of the run-in phase was to permit thebody to gradually adapt to exercise and to avoid soreness, injury,and discouragement.All aerobic activities were performed on a cycle ergometer ortreadmill. Participants were free to vary the machine used fromone visit to the next. Exercise intensity was standardized by usingheart rate monitors (Polar Electro Oy) that displayed the participant’s heart rate and emitted a warning signal when the heartrate was outside the prescribed training zone, thus guiding theparticipant in adjusting the workload up or down to achieve thedesired intensity. During the run-in phase, participants exercisedat a target intensity of 60% of maximum heart rate (defined bymaximum heart rate achieved during the maximal treadmill exercise test performed at baseline). This corresponded to a moderate exercise intensity of about 50% of the maximum oxygenconsumption. Progression during the intervention phase wasmore rapid than during the run-in phase. The intensity and duration of exercise were increased on a weekly basis (AppendixTable 4).Resistance TrainingResistance training was divided into a prerandomizationrun-in phase (weeks 1 to 4) and a postrandomization intervention phase (weeks 5 to 26). The aim of the run-in phase was tobuild strength gradually without developing undue muscularsoreness or injury. This was accomplished by use of light weightsand a high number of repetitions.Resistance exercises were performed on weight machines.Throughout the resistance training program, participants alternated between the exercises of group A and those of group Bshown in Appendix Table 5. Participants were instructed to exhale while lifting a weight and inhale while lowering it, to minimize blood pressure excursions, and to rest for 2 to 3 minutesbetween sets. Warm-up and cool-down were the same as foraerobic training.During the run-in phase, participants performed 1 set perresistance exercise twice weekly for the first 2 weeks and 2 sets ofeach resistance exercise twice weekly during weeks 3 and 4.Weight or resistance was increased by 5 to 10 pounds when theparticipant could perform more than 15 repetitions while maintaining proper form. The third weekly session of the run-in phaseinvolved only aerobic exercise, not resistance exercise. The tranAnnals of Internal MedicineW-66 18 September 2007 Annals of Internal Medicine Volume 147 • Number 6 www.annals.orgCollection and assembly of data: G.P. Kenny, N.G. Boule´, H. Tulloch,Downloaded from https://annals.org by guest on 02/14/2020sition from the run-in phase to the intervention phase involved 4changes in the exercise prescription: increasing frequency of resistance training from 2 to 3 days per week, increasing the number of sets from 2 to 3, increasing the amount of weight lifted,and decreasing the number of repetitions. During the intervention phase, weight or resistance for a given exercise was increasedby 5 to 10 pounds when the participant could perform morethan 8 repetitions of that exercise while maintaining proper form,and it was decreased by 5 to 10 pounds if the participant couldnot perform at least 8 repetitions of that exercise while maintaining proper form.Combined Aerobic and Resistance TrainingThis group performed the full aerobic and resistance training programs as described earlier. The aerobic and resistancecomponents were performed on the same days, in varying orders.Appendix Table 1. Changes in Hemoglobin A1c Value*Group Mean (SD) Hemoglobin A1cValue [Patients], % [n]†Absolute Change inHemoglobin A1c Valuefrom Baseline to 6Months (95% CI),percentage pointsPValueAdjusted Change inHemoglobin A1c Valuefrom Baseline to 6Months (95% CI),percentage pointsPValueBaseline 3 mo 6 moOverall Combined exercise groupAerobic training groupResistance training groupControl groupCombined exercise vs. aerobictraining7.46 (1.48) [64]7.41 (1.50) [60]7.48 (1.47) [64]7.44 (1.38) [63]6.99 (1.56) [60]7.00 (1.59) [58]7.35 (1.57) [62]7.33 (1.49) [62]6.56 (1.55) [58]6.98 (1.50) [49]7.18 (1.52) [56]7.51 (1.47) [59]0.90 (1.15 to 0.64)0.43 (0.70 to 0.17)0.30 (0.56 to 0.05)0.07 (0.18 to 0.32)0.0010.0020.0180.57–––––––– – – – – – 0.46 (0.83 to 0.09) 0.014Combined exercise vs. resistancetraining– – – – – 0.59 (0.95 to 0.23) 0.001 Aerobic training vs. controlResistance training vs.control––––––––––0.51 (0.87 to 0.14)0.38 (0.72 to 0.22)0.0070.038 Baseline hemoglobin A1cvalue >7.5% Combined exercise groupAerobic training groupResistance training groupControl groupCombined exercise vs. aerobictraining8.44 (1.04) [30]8.31 (1.16) [28]8.29 (1.14) [36]8.30 (1.03) [33]7.64 (1.32) [28]7.51 (1.45) [27]8.06 (1.48) [35]8.06 (1.38) [33]7.02 (1.35) [27]7.47 (1.33) [21]7.80 (1.42) [30]8.28 (1.39) [31]1.42 (1.83 to 1.01)0.83 (1.28 to 0.38)0.49 (0.87 to 0.10)0.02 (0.40 to 0.36)0.0010.0010.0130.90–––––––– – – – – – 0.59 (1.20 to 0.02) 0.058Combined exercise vs. resistancetraining– – – – – 0.93 (1.49 to 0.37) 0.001 Aerobic training vs. controlResistance training vs.control––––––––––0.81 (1.40 to 0.21)0.46 (1.00 to 0.08)0.0080.094 Baseline hemoglobin A1cvalue