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Effects of Performing Resistance ExerciseBefore Versus After Aerobic Exercise onGlycemia in Type 1 Diabetes

JANE E. YARDLEY, PHD1,2GLEN P. KENNY, PHD1,2

BRUCE A. PERKINS, MD, MPH3

MICHAEL C. RIDDELL, PHD4

JANINE MALCOLM, MD5,6PIERRE BOULAY, PHD7

FARAH KHANDWALA, MSC8

RONALD J. SIGAL, MD, MPH6,8,9

OBJECTIVEdTo determine the effects of exercise order on acute glycemic responses in indi-viduals with type 1 diabetes performing both aerobic and resistance exercise in the same session.

RESEARCH DESIGN AND METHODSdTwelve physically active individuals with type1 diabetes (HbA1c 7.1 6 1.0%) performed aerobic exercise (45 min of running at 60% _VO2peak)before 45 min of resistance training (three sets of eight, seven different exercises) (AR) or per-formed the resistance exercise before aerobic exercise (RA). Plasma glucose was measured duringexercise and for 60 min after exercise. Interstitial glucose was measured by continuous glucose

monitoring 24 h before, during, and 24 h after exercise.RESULTSdSignificant declinesin bloodglucose levelswere seen in AR but notin RA through-out the first exercise modality, resulting in higher glucose levels in RA (AR = 5.5 6 0.7, RA =9.26 1.2 mmol/L, P= 0.006 after 45 min of exercise). Glucose subsequentlydecreased in RA andincreased in AR over the course of the second 45-min exercise bout, resulting in levels that werenot significantly different by the end of exercise (AR = 7.5 6 0.8, RA = 6.9 6 1.0 mmol/L, P=0.436). Although there were no differences in frequency of postexercise hypoglycemia, theduration (105 vs. 48 min) and severity (area under the curve 112 vs. 59 units z min) of hypo-glycemia were nonsignificantly greater after AR compared with RA.

CONCLUSIONSdPerforming resistance exercise before aerobic exercise improves glycemicstability throughout exercise and reduces the duration and severity of postexercise hypoglycemiafor individuals with type 1 diabetes.

Diabetes Care 35:669675, 2012

Regular physical activity is associatedwith greater longevity and lowerfrequency and severity of diabetes

complications in individuals with type 1diabetes (1,2). The type of exercise to rec-ommend for potential improvements inglycemia in this population is still uncer-tain. Intervention studies of aerobic exer-cise training have not shown consistenteffects on blood glucose control, as

measured by HbA1c (3). Two small (n =810) studies examiningthe chronic effectsof resistance exercise training have found;1 percentage point reductions in HbA1c(4,5).

Including short bursts of intense activ-ity, where anaerobic metabolism plays amajor role in providing fuel, may assist inpreventing hypoglycemia during and up to2 h postexercise in individuals with type 1

diabetes (69). However,two studies usingcontinuous glucose monitoring (CGM)systemssuggested that the riskof nocturnalhypoglycemia after such exercise sessions isincreased (10,11) and perhaps even morethan after moderate aerobic activity (11).The effects of resistance training, anotherform of anaerobicexercise, on acute glycemiain type 1 diabetes is currently unclear. Inone study, insulin sensitivity (measuredby euglycemic clamp) was unchanged 12and 36 h after resistance exercise, therebysuggesting that resistance exercise may not

cause as much of a postexercise hypogly-cemic response compared with aerobicexercise (12).

The American Diabetes AssociationStandards of Medical Care (13) encour-ages individuals with diabetes to followthe U.S. Department of Health and Hu-man Services Physical ActivityGuidelines(14), which suggest including both aero-bic and resistance exercise in fitness pro-grams. Individuals who are activelyengaged in training often wish to performboth types of exercise within the same

session. We previously found that aerobicexercise causes a more rapid decrease inblood glucose and a greater need for car-bohydrate supplementation during exer-cise than resistance exercise (15). We areunaware of previous research examiningthe acute effects in individuals with type 1diabetes of combining these exercise mo-dalities in a single session or whetherthere is an advantage related to the orderin which they are undertaken. We soughtto determine if the order of exercise incombined sessions has a differential effecton blood glucose during and postexercise(as measured by CGM) in this population.

In individuals without diabetes, per-forming aerobic exercise immediatelyafter resistance exercise results in an in-creased reliance on lipids as a fuel sourceduring activity (16). We therefore hypoth-esized that performing resistance exercisebefore aerobic exercise would lead to lessof a decline in blood glucose during exer-cise in individuals with type 1 diabetesthan when exercise is performed in theopposite order. Because performing resis-tanceexercisefirstmayresultin a diminished

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From the 1Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Ontario,Canada;the 2Institute of Population Health, Universityof Ottawa, Ottawa, Ontario, Canada;the 3UniversityHealth Network, Toronto General Hospital, Toronto, Ontario, Canada; the 4School of Kinesiology andHealthScience, YorkUniversity,Toronto,Ontario, Canada;the 5Faculty of Medicine, University of Ottawa,Ottawa, Ontario, Canada; the 6Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; the7Champlain Diabetes Regional Coordination Centre, Ottawa, Ontario, Canada; 8Alberta Health Services,Calgary, Alberta, Canada; and the 9Departments of Medicine, Cardiac Sciences and Community HealthSciences, and Faculties of Medicine and Kinesiology, University of Calgary, Calgary, Alberta, Canada.

Corresponding author: Ronald J. Sigal, [email protected] 28 September 2011 and accepted 19 December 2011.DOI: 10.2337/dc11-1844This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10

.2337/dc11-1844/-/DC1. 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly

cited,theuse iseducationaland notforprofit,and the workis notaltered.See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

care.diabetesjournals.org DIABETES CARE, VOLUME 35, APRIL 2012 669

C l i n i c a l C a r e / E d u c a t i o n / N u t r i t i o n / P s y c h o s o c i a l R e s e a r c h

O R I G I N A L A R T I C L E
mailto:[email protected]://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://creativecommons.org/licenses/by-nc-nd/3.0/http://creativecommons.org/licenses/by-nc-nd/3.0/http://creativecommons.org/licenses/by-nc-nd/3.0/http://creativecommons.org/licenses/by-nc-nd/3.0/http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1mailto:[email protected]

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reliance on carbohydrate for fuel duringexercise, we anticipated that less nocturnalhypoglycemia would be found where aer-obic exercise was preceded by resistanceexercise.

RESEARCH DESIGN ANDMETHODSdThe University of Ottawa

and Ottawa Hospital Research EthicsBoards approved the experimental pro-tocol. We recruited 12 nonobese adultswith type 1 diabetes. Participants per-formed aerobic and resistance exercise atleast three times per week and had beendoing so for at least 6 months (Table 1).

Experimental designThe research took place in the Humanand Environmental Physiology ResearchUnit at the University of Ottawa. Afterbeing informed of the purpose, protocol,and possible risks of the study, participantsgave written consent and completed phys-ical activity readiness questionnaires(American Heart Association/AmericanCollege of Sports Medicine Health/FitnessFacility Preparticipation Screening Ques-tionnaire). Hand-held glucose meters(OneTouch Ultra, Lifescan, Johnson &

John son, Milpitas, CA) and test strips(with identical code) were provided forcapillary glucose tests.

On a separate visit, participants un-derwent an incremental workload runningtest on a treadmill with a monitored elec-

trocardiogram (Quinton Q4500, Quinton,Bothell, WA) to determine peak oxygenconsumption ( _VO2peak). _VO2peak was de-termined by measuring the volume and

concentration of expired oxygen and car-bon dioxide (AMETEK model S-3A/1and CD 3A, Applied Electrochemistry,Pittsburgh, PA). Muscular strength (eightrepetition maximum [8-RM]) was re-corded as the maximum weight that partic-ipants could lift eight times with good formfor chest press (pectoralis major), leg press

(quadriceps, biceps femoris, gluteus maxi-mus), seated row (latissimus dorsi, rhom-boids, trapezius), leg curl (biceps femoris),shoulder press (deltoids), and lat pull-down (latissimus dorsi). A venous bloodsample was drawn for determination ofHbA1c, which was measured by automatedheterogeneous immunoassay with latex-enhanced turbidimetric detection on aRoche Cobas Integra 800 analyzer (RocheDiagnostics Corp., Indianapolis, IN).

CGMThe CGMS System Gold (Medtronic,Northridge, CA) was used in this study.Participants were blinded to their glucosevalues and could not change their regularbehavior patterns based on real-time glu-cose monitoring. Twenty-four hours be-fore each experimental session, the CGMsensor was inserted subcutaneously in theabdomen or in theupper gluteal area. Thesame insertion site was used for bothtrials. Training on calibration and opera-tion of the CGM units was provided.Participants performed capillary glucosetests and calibrated the CGM unit four

times daily using the hand-held glucosemeter provided. On the third day, 24 hpostexercise, participants removed thesensors and the researchers retrieved themonitors. Data were downloaded using aMedtronicCom-Station and Minimed Sol-utions Software version 3.0 (Medtronic).

Participants maintained diaries offood intake and insulin administrationwhile wearing the CGM sensor. They atethe same breakfast, same lunch, and samesupper each day of sensor wear and kepttheir insulin doses the same each of thesedays to the greatest extent possible. Par-ticipants avoided exercise (apart from thatperformed in our laboratory) for 24 hbefore inserting the sensor (48 h beforeeach study exercise session) as well asduring the 3 days of sensor wear. Theyalso avoided caffeine and alcohol duringthis time.

Experimental sessionsParticipants arrived at the laboratory at1600 h. Intravenous catheters were inser-ted soon after arrival. Exercise started at1700h for all participants. Each participant

performed two experimental sessions inrandom order separated by at least 5days:

1. Aerobic exercise before resistance ex-ercise session (AR): A 45-min bout ofmoderate-intensity aerobic exercise(treadmill running at 60% of their

predetermined _VO2peak), followed by a

45-min bout of resistance training(three sets of eight repetitions with 90 sof rest between sets).

2. Resistance exercise before aerobic ex-ercise session (RA): The same exercisesas above were performed, with the re-sistance exercise completed before theaerobic exercise.

Sessions were followed by 1 h ofmonitored recovery in a resting state.

Women were using monophasic oralcontraceptives and were tested duringthe active pill consumption phase.

MeasurementsOn the days that exercise was scheduled(day 2 of each 3-day monitoring period),participants were asked to decrease theirinsulin doses (a 10% decrease in long- orintermediate-acting for patients receivingmultiple daily injections and a 50% de-crease in basal rate 1 h pre-exercise forpatients receiving a continuous subcuta-neous insulin infusion). A further 25%basal rate decrease was made for continu-

ous subcutaneous insulin infusion patientsif their capillary glucose was #5 mmol/Lupon arrival at the laboratory. Adjustedrates were maintained throughout exercise.Standardized snacks (Glucerna ChocolateGraham Snack Bars, 150 calories, 25 g ofcarbohydrate; Abbott Laboratories, AbbottPark, IL) were provided and consumed at1600 h each day of monitoring.

Before starting exercise, participantswere required to have blood glucose levelsbetween 5.5 and 13.9 mmol/L. Capillaryglucose tests were performed upon arrivalat the laboratory, 30 min before and im-mediately before exercise. If capillary glu-cose levels were,4.5 mmol/L,participantswere provided with 32 g of glucose (Dex4,

AMG Medical, Montreal , QC, Canada)before levels were checked again 15min later. If initial readings were between4.5 and 5.4 mmol/L, participants weregiven16 g of glucose. These steps were repeateduntil a level of$5.5 mmol/L was achieved.

Glucose concentrations during exer-cise were monitored by applyinga drop ofvenous blood to a test strip inserted in thestudy hand-held glucose meter when

Table 1dParticipant characteristics

n ormean 6 SD

Patients 12

Sex

Male 10

Female 2Age (years) 31.8 6 15.3

Height (m) 1.77 6 0.07

Weight (kg) 79.2 6 10.4

BMI (kg/m2) 25.3 6 3.0_VO2peak

(mL O2 z kg21

z min21) 51.2 6 10.8

HbA1c (%) 7.1 6 1.1

Diabetes duration (years) 12.56 10.0

Insulin delivery

Multiple daily injections 5

Continuous subcutaneous

insulin infusion 7

670 DIABETES CARE, VOLUME 35, APRIL 2012 care.diabetesjournals.org

RA/AR order in type 1 diabetes

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venous blood samples were collected.When levels were ,4.5 mmol/L, exercisewas interrupted and participants wereprovided with 16 g of glucose. Capillaryglucose tests were then performed every10 min, and an additional 16 g of glucosewas provided when necessary until a levelof$5.5 mmol/L was achieved and exer-

cise resumed. Oxygen consumption wasmeasured using a portable gas analysissystem (Oxycon Mobile, Jaeger, Hoechberg,Germany). Energy expenditure was calcu-lated as described elsewhere (17).

Blood analysesVenous blood samples were collected atbaseline, 5, 10, 15, 30, 45, 50, 55, 60, 75,and 90 min during exercise and at 5, 10,15, 20, 30, 40, 50, and 60min after exercise.Blood was drawn using 5 mL sterile plasticsyringes and transferred immediately into5.4 mL plasma (K

2EDTA) BD Vacutainer

tubes (BD, Franklin Lakes, NJ), mixed byinversion and centrifuged immediately.Plasma aliquots were transferred into 1.5mL microcentrifuge tubes and stored at2808C until analyzed. Plasma glucose con-centrations were determined using thehexokinase timed end point method onthe Beckman Coulter Unicel DxC600 Syn-chron Clinical Analyzer (Beckman CoulterInc., Fullerton, CA) with SYNCHRON CXSystems GLUCOSE reagent (Cat#442640).

Statistical analyses

Exercise and recovery periods were exam-ined separately. Plasma glucose concentra-tion was compared between treatmentsusing two-way repeated-measures ANOVAwith the factors of time (exercise: 5, 10,15, 30, 45, 50, 55, 60, 75, and 90 min;recovery: 5, 10, 15, 20, 30, 40, 50, and60 min) and treatment (RA or AR).Pairedsample t tests were used to perform pair-wise post hoc comparisons betweentreatments for each time point to examinewithin-treatment changes from baselineand changes throughout recovery. Thelevel of significance was set at 0.05. Energyexpenditure during the exercise sessions(including the recovery) was comparedusing a paired sample t test.

CGM data were grouped and sum-marized as follows: 24 h and overnight(2400 to 0600 h) pre-exercise, as well as24 h and overnight postexercise. Hypo-glycemia was defined as any value ,3.5mmol/L detected by CGM, and values.10.9 mmol/L were categorized as hy-perglycemic. Total time spent in hypogly-cemia, euglycemia, and hyperglycemia forthe predetermined periods and the area

under the curve (AUC, defined as the ab-solute distance from the described limits,multiplied by the time spent outside thoselimits) for time spent hypo- and hypergly-cemic was determined along with the max-imum, minimum, and mean interstitialglucose for each time period. Variableswere compared between exercise treat-

ments, and pre- and postexercise valueswere compared within treatments using re-lated-samples Wilcoxon signed rank tests.These tests were also used to examine dif-ferences in insulin and carbohydrate in-take (calculated from the participantsfood and insulin diaries) between dayswithin exercise treatments (day 1 vs. 2),and between exercise treatments (days 1through 3). Pearson correlation analyseswere performed comparing capillary glu-cose values recorded by the participantsduring nonexercise periods to CGM datato assess the accuracy of the sensorsthroughout each 3-day measuring period.

Analyses were performed using SPSS 18.0software (SPSS Inc., Chicago, IL). Data arepresented as means 6 SD.

RESULTSdEnergy expenditure wasmeasured during exercise and recoverytogether for both sessions in 9 of the 12participants. There were no differences inenergy expenditure between AR (4,2776729 kJ) and RA (4,247 6 589 kJ).

Plasma glucose

Plasma glucose levels for exercise andrecovery (Supplementary Table 1) areplotted in Fig. 1. A significant effect oftime (P = 0.001) and an interaction oftreatment and time (P = 0.004) werefound in examining plasma glucose levelsduring exercise (Fig. 1). Differences be-tween treatments were not significant atbaseline. The aerobic exercise performedin the AR treatment caused a substantialdecline in blood glucose concentration,resulting in plasma glucose levels thatwere lower than baseline within the first10 min of exercise, persisting until theend of aerobic exercise (9.16 2.4 at base-line; 5.5 6 2.4 mmol/L at 45 min; P,0.01) and continuing into resistance ex-ercise. Glucose then increased during re-sistance exercise, producing levels thatwere similar to baseline by the end of ex-ercise. Conversely, the RA treatment didnot produce significant changes frombaseline during resistance exercise. Afterthe change in exercise modality in RA,glucose levels were only significantly dif-ferent from baseline after 75 (P = 0.044)and90(P= 0.018) min of exercise. Glucose

was lower in the AR treatment than inthe RA treatment until the end of exer-cise, with differences achieving statisti-cal significance between 30 and 60 min(P, 0.05).

During the postexercise recovery pe-riod, there was a significant effect of time(P, 0.01) for changes in plasma glucose,

but no effect of treatment or interaction oftreatment and time. Significant increasesin plasma glucosefrom the end of exercisewere seen throughout recovery after ARwhere none were observed after exercisein RA (Fig. 1).

Carbohydrate intake and insulindosageTotal daily insulin doses did not differsignificantly between treatments on thefirst 2 days of CGM wear before theexperimental exercise session, or betweenthe first and second day within eachtreatment. Insulin adjustments for exer-cise were similar between treatments(Supplementary Table 2). On the day af-ter the exercise testing session, insulin in-take was lower after the AR sessioncompared with RA (36.1 6 16.3 vs.38.8 6 18.5 units, P= 0.028). Ten of 12participants required carbohydrate sup-plementation during the AR session com-pared with only 6 of 12 during RA;however, there were no statistically signif-icant differences between groups in totalcarbohydrate intake during exercise and

recovery in the laboratory (Supplemen-tary Table 3) and in the 6 h after exercise(Supplementary Table 4).

Interstitial glucose levelsPearson correlations between capillaryglucose readings from nonexercise peri-ods and sensor readings over the moni-toring period were 0.95 for AR and 0.91for RA (P, 0.001). There were no signif-icant differences between treatments withrespect to hypoglycemia and hyperglyce-mia (number of excursions, time, AUC) aswell as mean, maximum, and minimumglucose on the night before or 24 h beforeexercise.

Mean postexercise overnight CGMprofiles are provided in Fig. 2. In the RAtreatment, average maximum nocturnalglucose levels were significantly lower af-ter exercise than the previous (nonexer-cise) night (pre-exercise = 9.5 6 3.0mmol/L, postexercise maximum = 8.8 64.0 mmol/L; P= 0.04). Within the AR treat-ment, there was a trend toward greater

AUC postexercise for noct urnal hypo-glycemia (P = 0.06) compared with RA.


Yardley and Associates
http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc11-1844/-/DC1

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Although the frequency of nocturnal hy-poglycemic events did not differ betweenthe two exercise sessions, theduration anddepth of hypoglycemia tended to be lon-ger and more severe after AR than after RA(Table 2).

CONCLUSIONSdThis study evalu-ated, in the context of a combined re-sistance and aerobic exercise session, theeffects of exercise order on blood glucoselevels in individuals with type 1 diabetes.

As we had anticipated, performing re-sistance exercise before aerobic exercise

rather than the reverse resulted in atten-uated declines in glucose concentrationduring exercise, fewer exercise-inducedhypoglycemic events, and less need forcarbohydrate supplementation. Further-more, we observed beneficial effects fromthissequenceon subsequent 12-h glycemictrends where the duration and severity of

hypoglycemia was reduced. The benefitsof performing resistance exercise beforeaerobic exercise instead of the reverse wereobserved despite overall energy expendi-ture being equal between experimentalsessions.

Resistance exercise is a primarily an-aerobic activity. Other types of high-intensity exercise combining aerobic andanaerobic metabolism (e.g., high intensitycycling) can increase the rate of glucoseappearance to a greater extent than therateof glucose utilization (seven and fourtimes, respectively) during exercise in

type 1 diabetes (18). This may cause glu-cose levels to increase during exercise,producing postexercise hyperglycemia ifintense exercise is sustained for 12 ormore minutes (19). Shorter anaerobic ex-ercise bouts (intermittent 4-s sprints or10-s sprints before or after low-intensityaerobic exercise) attenuated declines in

blood glucose both during and after exer-cise when combined with low-intensity(40% _VO2peak) cycling (68). Elevatedglucoseproduction fromveryhigh-intensityexercise is generally attributed to increasedlevels of circulating epinephrine [known totriple with short sprints (6,8,9) and increaseupto 14 times its resting value (18)after 12

min of exhaustive cycling] and norepi-nephrine, which augment glycogenolysisthroughout exercise and early recovery(18,19).

Although we did not measure cate-cholamines during the sessions, responsesto high-intensity exercise are known to becomparable (18,20) or slightly attenuated(19,21) in individuals with type 1 diabe-tes compared with nondiabetic counter-parts. Catecholamines can increase tothree or four times resting values duringmoderate-intensity resistance exercise inindividuals without diabetes (22), withresponses increasing in proportion toexercise intensity (23). If our participantsexperienced similar responses to resistanceexercise as individuals without diabetes,then increases in epinephrine may havecontributed to the attenuated rate of de-cline in blood glucoseduring thefirst 15minof aerobic exercise in RA, and to the in-crease in glucose during resistance exercisein AR (Fig. 1). The latter should be inter-preted with caution, because most partic-ipants needed glucose supplements toprevent hypoglycemia during aerobic ex-

ercise in this session.It is also possible that exercise-related

growth hormone (GH) secretion differedbetween treatments, potentially affectingfuel selection during exercise. Goto et al.(24) found that in nondiabetic individuals,endurance exercise performed before re-sistance exercise produced lower GH

Figure 1dMean 6 SE plasma glucose during exercise and recovery for aerobic exercise per-formed before resistance exercise (AR, dashed line with ) and resistance exercise performedbefore aerobic exercise (RA, solid line with C) (n = 11). *Difference from baseline during ex-ercise where P , 0.05. Difference between conditions where P , 0.05. Change throughoutrecovery from end-exercise level where P , 0.05.

Figure 2dMean glucose (n = 12) as measured by continuous glucose monitoring from 1 to 12 h after exercise following aerobic exercise performedbefore resistance exercise (AR, dashed line) and resistance exercise performed before aerobic exercise (RA, solid line). (A high-quality color rep-resentation of this figure is available in the online issue.)



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secretion than resistance exercise alone.They also found that resistance exerciseperformed 20 min or less before endur-ance exercise produced elevated levels ofGH and greater rates of lipolysis duringthe subsequent aerobic activity com-pared with endurance exercise alone(16). Because higher GH levels areknown to decrease muscle glucose up-take and increase lipolysis in nondia-betic individuals (25), this may havebeen a factor in the attenuated declines

in blood glucose during aerobic activityin RA.

High-intensity cycling increasesblood lactate levels during and up to 40minafterexercise in individualswith type1 diabetes (6,7,9,18,19). We are unawareof published data describing lactate re-sponses to resistance exercise in this pop-ulation. Resistance exercise protocolssimilar to the one we used have producedlactate concentrations up to four timesthose measured at rest, with levels re-maining significantly higher than base-line until 30 min postexercise in trainednondiabetic individuals (26). Because el-evated lactate could serve to increasegluconeogenesis (7), it could be a con-tributing factor in the attenuated declinein glucose during the first 15 min of aer-obic exercise in RA as well as in theincreases in postexercise glucose levelsin AR.

Studies suggest that high-intensity ex-ercise may be associated with a greater fre-quency of nocturnal hypoglycemia in type1 diabetic individuals (10,11). Our partic-ipants experienced nocturnal hypoglycemia

as frequently postexercise as on non-exercise nights. Nocturnal hypoglycemiahas been identified as a risk inherentwith intensive insulin therapy (27), andit is possible that overnight hypoglyce-mia in our study was more related toinsulin therapy than to exercise. It isnoteworthy that hypoglycemic eventsoccurring after AR tended to be longerand more severe than those experiencedin RA, as demonstrated by a greater AUC.Studies using glucose clamp found that

counter-regulatory responses to subse-quent hypoglycemia were blunted afterexercise, even in the absence of significantchanges in glucose levels during exercise(28). In addition, even mild hypoglycemia(3.9 mmol/L) in nondiabetic individualsis sufficient to elicit counter-regulatoryreactions that can blunt neuroendocrineresponses to subsequent hypoglycemiawithin 24 h (29). Because decreases inblood glucose were greater during AR(reaching a mean of 5.5 6 2.4 vs. 6.9 63.1 mmol/L in RA), it is plausible that sub-sequent responses to declining bloodglucose could have been subject to impair-ment after exercise.

Although there are advan tages toadmitting study subjects the night beforetesting to control participant activity andfood intake, we chosea study design morereflective of real-life conditions. Partici-pants controlled their meals and insulinbut were asked to eat the same breakfast,lunch, and dinner at the same time forevery day of sensor wear and to matchtheir insulin intake as closely as possible.Exercise took place at 1700 h when many

individuals who work during the day optto exercise, unlike several other studieswhere midmorning exercise was per-formed (69,18,19).

Several aspects of resistance trainingin type 1 diabetic individuals requirefurther scrutiny. Glucose responses maybe different if exercise is performed at

another time of day because hormone andexogenous insulin concentrations are bothlikely to be different. Our participantswerefit, habitual exercisers, and the effectsof exercise may be less pronounced inunfit individuals exercising at the samerelative intensity because the activitywould be at a lower absolute intensity. Innondiabetic subjects running at very highrelative intensity, glucose production andcatecholamine concentrations increasemore in athletes than in physically un-trained individuals, resulting in hypergly-cemia after exercise in the former groupbecause glucose production falls moreslowly than glucose utilization when ex-ercise ends (30). Further research on dif-ferent subpopulations of type 1 diabeticindividuals, including those with lowerfitness levels and poorer glycemic control,is warranted.

This study is limited by its smallsample size (n = 12), which may have pre-vented us from finding all of the signifi-cant differences in plasma glucose levelsduring exercise. To examine our partici-pants in a real-life scenario, we compro-

mised a certain amount of experimentalcontrol such as having complete controlover all food and insulin intake. The abilityto interpret the data would have been im-proved by having catecholamine, lactate,and GH measurements. Finally, having arelativelyfit sample with moderate to goodcontrol of their diabetes makes the appli-cability of the outcomes to individualswho are inactive or have poor glycemiccontrol uncertain.

In summary, ourfindings suggest thattrained individuals with type 1 diabeteswho perform both resistance and moder-ate aerobic exercise should consider per-forming their resistance exercise first ifthey tend to develop exercise-associatedhypoglycemia because doing so may at-tenuate declines in glucose levels duringsubsequent aerobic exercise. This order ofexercise could lead to a lower reliance onglucose supplementation during exerciseand might also decrease the severity of po-tential nocturnal hypoglycemia. Converse-ly, individuals having exercise-associatedhyperglycemia may wish to perform aer-obic exercise before resistance training.

Table 2dSummary of overnight (2400 to 0600 h) continuous glucose monitoring

data for the night before and the night after exercise*

AR RA

(n = 12) (n = 12)

Night before exercise session

Participants experiencing nocturnal hypoglycemia 4 (30) 5 (42)

Total hypoglycemic episodes 7 4Duration of hypoglycemia per episode (min) 97.56 84.9 47.1 6 32.8

AUC for hypoglycemia per episode (mmol z min) 112.3 6 97.6 42.3 6 41.9

Overnight glucose (mmol/L) 6.7 6 3.2 6.9 6 2.7

Night after exercise session

Participants experiencing nocturnal hypoglycemia 3 (25) 4 (30)

Total hypoglycemic episodes 5 6

Duration of hypoglycemia per episode (min) 105 6 116 48 6 68

AUC for hypoglycemia per episode (mmol z min) 110 6 146 59 6 110

Mean overnight glucose (mmol/L) 6.3 6 2.4 6.7 6 3.1

Categoric data are expressed as n or n (%), and continuous data are presented as mean 6 SD. *Nosignificant differences between pre- and postexercise, or between exercise conditions. Defined as glucose,3.5 mmol/L.



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Both approaches should still be accom-panied by careful monitoring of bloodglucose levels, both during and afterexercise.

AcknowledgmentsdJ.E.Y. was supporte dby a Doctoral Student Award from the Cana-dian Diabetes Association, an ExcellenceScholarship from the University of Ottawa,and funds from the Ottawa Hospital ResearchInstitute Research Chair in Lifestyle Research.R.J.S. was supported by a Health Senior Scholaraward from the Alberta Heritage Foundation forMedical Research. G.P.K. was supported by aUniversity of Ottawa Research Chair. This studywas conducted in the Human and Environ-mental Physiology Research unit funded by aCanada Foundation for Innovation LeadersOpportunity Fund (grant held by G.P.K.). B.A.P.was supported by a Canadian Diabetes Associ-ation Research Scholar Award.

B.A.P. has received consultation fees fromGlaxoSmithKline; honoraria from Johnson &Johnson, sanofi-aventis, Medtronic, and NovoNordisk; and grant support from BoehringerIngelheim and Medtronic. M.C.R. has receivedspeakers fees from Medtronic Canada. Allsensors and continuous glucose monitor-ing systems were provided by MedtronicCanada. Glucerna Snack Bars were providedby Abbott Laboratories. Glucometers and teststrips were provided by Johnson & Johnson.No other potential conflicts of interest rele-vant to this article were reported.

J.E.Y. contributed to the conception anddesign of the project, contributed to discussion,

collected and analyzed the data, and drafted,reviewed, and edited the manuscript. G.P.K.,B.A.P., M.C.R., and R.J.S. contributed to theconception and design of the project, re-searched data, contributed to discussion, andreviewedand edited the manuscript. J.M.andP.B. contributed to the discussion and re-viewed and edited the manuscript. F.K. tookthe lead in data analysis, contributed to thediscussion, and reviewed and edited the man-uscript. R.J.S. is the guarantor of this work and,as such, had full access to all the data in thestudy and takes responsibility for the integrityof the data and the accuracy of the dataanalysis.

Parts of this study were presented in ab-stract form at the annual Professional Con-ference of the Canadian Diabetes Association,Edmonton, Alberta, Canada, 2023 October2010.

The authors thank the study partici-pants for their time and effort, and NadiaBalaa, University of Ottawa, for technicalassistance.

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