Results From a EuropeanMulticenter Randomized Trial ofPhysical Activity and/or HealthyEating to Reduce the Risk ofGestational Diabetes Mellitus: TheDALI Lifestyle PilotDiabetes Care 2015;38:1650–1656 | DOI: 10.2337/dc15-0360

OBJECTIVE

Ways to prevent gestational diabetes mellitus (GDM) remain unproven. We com-pared the impact of three lifestyle interventions (healthy eating [HE], physicalactivity [PA], and both HE and PA [HE+PA]) on GDM risk in a pilot multicenterrandomized trial.

RESEARCH DESIGN AND METHODS

Pregnant women at risk for GDM (BMI ‡29 kg/m2) from nine European countrieswere invited to undertake a 75-g oral glucose tolerance test before 20 weeks’gestation. Those without GDM were randomized to HE, PA, or HE+PA. Womenreceived five face-to-face and four optional telephone coaching sessions, basedon the principles of motivational interviewing. A gestational weight gain (GWG)<5 kg was targeted. Coaches received standardized training and an interventiontoolkit. Primary outcome measures were GWG, fasting glucose, and insulin sen-sitivity (HOMA) at 35–37 weeks.

RESULTS

Among the 150 trial participants, 32% developed GDM by 35–37 weeks and 20%achieved GWG <5 kg. HE women had less GWG (22.6 kg [95% CI24.9,20.2]; P =0.03) and lower fasting glucose (20.3mmol/L [20.4,20.1]; P = 0.01) than those inthe PA group at 24–28 weeks. HOMA was comparable. No significant differencesbetween HE+PA and the other groups were observed.

CONCLUSIONS

An antenatal HE intervention is associated with less GWG and lower fasting glu-cose comparedwith PA alone. These findings require a larger trial for confirmationbut support the use of early HE interventions in obese pregnant women.

Gestational diabetes mellitus (GDM) is associated with increased risk of adverseperinatal outcomes, with a continuous relationship between glycemia on oral glu-cose tolerance test (OGTT) and pregnancy outcome (1). Obesity in pregnancy andexcess gestational weight gain (GWG) are associated with similar adverse pregnancyoutcomes, which are additional to any harm from antenatal hyperglycemia (2).

1Institute of Metabolic Science, AddenbrookesHospital, Cambridge, U.K.2University of Western Sydney, Campbelltown,NSW, Australia3Department of Public and Occupational Health,EMGO+ Institute for Health and Care Research, VUUniversityMedicalCenter,Amsterdam, theNetherlands4KU Leuven Department of Development andRegeneration: Pregnancy, Fetus and Neonate,Gynaecology and Obstetrics, University Hospi-tals Leuven, Leuven, Belgium5Institut de Recerca de l�Hospital de la Santa Creui Sant Pau, Barcelona, Spain6CIBERBioengineering,BiomaterialsandNanotech-nology, Instituto de Salud Carlos III, Madrid, Spain7National University of Ireland, Galway, Ireland8Department of Obstetrics and Gynecology,Medizinische Universitaet Graz, Graz, Austria9Gender Medicine Unit, Division of EndocrinologyandMetabolism, Department of Internal MedicineIII, Medical University of Vienna, Vienna, Austria10Center for Pregnant Women with Diabetes,Rigshospitalet, University of Copenhagen, Co-penhagen, Denmark11Odense University Hospital, Odense, Denmark12Universita Degli Studi di Padova, Padua, Italy13AziendaOspedaliero-UniversitariaPisana,Pisa, Italy14Department of Obstetrics and Women’s Diseases,PoznanUniversityofMedical Sciences,Poznan,Poland15Recherche en Sante Lawson SA, Bronschhofen,Switzerland16BAPHealthOutcomesResearch SL, Oviedo, Spain17Department ofMedical Psychology, VUUniver-sity Medical Center and Academic Medical Cen-ter, Amsterdam, the Netherlands

Corresponding author: David Simmons,da.simmons@uws.edu.au.

Received 18 February 2015 and accepted 12May2015.

Clinical trial reg.no. ISRCTN70595832,www.isrctn.org.

This article contains Supplementary Data onlineat http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc15-0360/-/DC1.

Aslide set summarizing thisarticle is availableonline.

© 2015 by the American Diabetes Association.Readers may use this article as long as the workis properly cited, the use is educational and notfor profit, and the work is not altered.

David Simmons,1,2 Judith G.M. Jelsma,3

Sander Galjaard,4 Roland Devlieger,4

Andre van Assche,4 Goele Jans,4

Rosa Corcoy,5,6 Juan M. Adelantado,5

Fidelma Dunne,7 Gernot Desoye,8

JurgenHarreiter,9 Alexandra Kautzky-Willer,9

Peter Damm,10 Elisabeth R. Mathiesen,10

Dorte M. Jensen,11 Lise Lotte Andersen,11

Annunziata Lapolla,12 Maria Dalfra,12

Alessandra Bertolotto,13

Ewa Wender-Ozegowska,14

Agnieszka Zawiejska,14 David Hill,15

Pablo Rebollo,16 Frank J. Snoek,17 and

Mireille N.M. van Poppel3

1650 Diabetes Care Volume 38, September 2015

CLINCARE/ED

UCATION/N

UTR

ITION/PSY

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Although obesity in pregnancy, ex-cess GWG, and GDM are associatedwith adverse outcomes, the evidencethat interventions to reduce theseharms are beneficial is mixed (3). In ameta-analysis, combined lifestyle inter-vention (physical activity [PA] withhealthy eating [HE]) was associatedwith reduced GWG (overall and insome studies), but not with improve-ment in perinatal outcomes (macroso-mia or cesarean delivery) or significantreduction in GDM rates (3). More recentlarge randomized controlled trials(RCTs) have shown no reduction in theincidence of GDM with lifestyle inter-vention, with limited differences inGWG between intervention and controlwomen (4–6), but potential reductionsin birth weight (5). Although preventionof excessive GWG and macrosomia arekey goals in such interventions, therehas been concern that too little mater-nal weight gain could be associated withan increased incidence of small-for-gestational-age babies and reduced off-spring fat-free mass (7). With thesecautions, it is clear that further trialsare needed to investigate efficacious ap-proaches that will reduce GWG and pro-gression to GDM, particularly in obesewomen.We now report on the findings from

the lifestyle pilot for DALI (Vitamin DAnd Lifestyle Intervention for GDM pre-vention) (8), undertaken to test the pro-cedures, methodology, and lifestyleinterventions for the forthcoming fullRCT within a European multicenter RCTof three different lifestyle approachesfor the prevention of GDM. The pilotreports on risk of GDM rather thanGDM itself and does not include the vi-tamin D intervention.

RESEARCH DESIGN AND METHODS

Overall Study DesignThe pilot study for DALI is a multicenterRCT of three different lifestyle ap-proaches that could prevent GDM. Thepilot was undertaken across 10 Euro-pean centers in nine countries, eachwith its own nutrition and PA culturalnorms. This diversity in backgroundpopulations was included to ensurethat the intervention was applicable indifferent settings and populations. Thestudy was approved by the relevantethics committees. The pilot was regis-tered as an RCT (ISRCTN70595832). The

primary outcomes were maternalweight gain (defined as the weightchange from baseline measurement tothe last measurement at 35–37 weeksof gestation), fasting glucose, and insulinsensitivity as derived from the HOMA at35–37 weeks (9). The pilot study was de-vised to recruit four women for each ofthe three interventions in each center(total n = 120).

ParticipantsPregnant women aged $18 years, be-fore 20 weeks of gestation with a pre-pregnancy BMI $29 kg/m2 (based onfeasibility following a review of Euro-pean obesity prevalence), were eligiblefor inclusion. Women were excludedfrom the study if they were diagnosedwith GDM by OGTT before randomiza-tion, using World Health Organization(WHO) 2013 criteria (fasting venousplasma glucose $5.1 mmol/L and/or1-h glucose $10 mmol/L and/or 2-hglucose$8.5 mmol/L) (10). Other exclu-sion criteria were pre-existing diabetes,inability to walk$100m safely, multiplepregnancy, requiring a complex diet, asignificant chronic medical condition orpsychiatric disease, and inability tospeak the major language of the countryof recruitment fluently or to conversewith the lifestyle coach in another lan-guage for which translated materialsexisted.

RecruitmentThe 10 centers were Cambridge (coordi-nating center), Galway, Amsterdam,Leuven, Poznan, Pisa/Padova (as onecenter), Barcelona, Vienna, Odense, andCopenhagen. A common informationsheet, in the local language, was givento eligible participants for considerationand the trial explained by the researchmidwife/nurse. Written consent was ob-tained for participation. The pilot studystarted in January 2012, and the last par-ticipant gave birth in August 2013.

ProceduresAfter signed consent, assessments weremade by the research midwife/nursebefore 20 weeks (screening/baseline),24–28 weeks, and 35–37 weeks of ges-tation and after delivery. The lifestyleintervention was delivered by a lifestylecoach. Where GDM developed afterbaseline, womenweremanaged accord-ing to local practice. Supplementary Fig. 1

provides a diagrammatic overview ofassessments and intervention.

RandomizationEligible women were randomly allo-cated to one of the three interventions(HE, PA, or both [HE+PA]) following anallocation schedule prestratified for in-tervention center, using a computerizedrandom number generator. Sealed opa-que envelopes (containing the interven-tion arm to which each participant wasallocated with a randomization number)were sent to each site by the DALI trialcoordinator (D.S.). After assurance of el-igibility, the personal details of the par-ticipant were provided to the lifestylecoach who opened the next randomiza-tion envelope. Those involved withmeasurements were kept blinded tothe intervention through noninvolve-ment and explicit training. Separationbetween coach and measurementsteam was assessed during site monitor-ing visits.

Lifestyle InterventionsAfter randomization, five face-to-faceand four optional telephone coachingsessions were scheduled for each partic-ipant, as shown in Supplementary Fig. 1.As previously described (8), coaching in-volved discussion of seven HE and/orfive PA “messages” based upon previouswork (11), as shown in Table 1. Mes-sages were supported by a “toolkit” forthe participant, including participanthandbook, educational materials (e.g.,adapted F.I.T.T. model [frequency, in-tensity, time, type]) based on AmericanCollege of Obstetricians and Gynecolo-gists (ACOG) guidelines (12), pedome-ters (Yamax Digiwalker SW-200, Tokyo,Japan), and flexible elastic dynabands(Thera-Band, Akron, OH). The messagedelivery was built upon behavioral the-ory principles (13), including patient em-powerment and cognitive behavioraltechniques inspired by motivational in-terviewing (14). At least four face-to-face coaching sessions were expectedto take place before the second mea-surement session, and the interventionwas completed by 35 weeks of gesta-tion. Standardization of the interventionwas achieved through a training pro-gram concluding with an observed ses-sion with an actor, provision of a deskfile with all materials and methods, anduse of a personal digital assistant (PDA;

care.diabetesjournals.org Simmons and Associates 1651

HTC HD7 Windows phone), with be-spoke software to provide a frameworkfor the session. A “paper” PDA includingall fields was available for when therewere any problems with the PDA.A key component was for women to

strive to achieve a maximum GWG of5 kg, as this is the lower limit of theweightgain recommended by the Institute ofMedicine (IOM) for those with a BMI$30 (15) and following the observationof better outcomes among Danish obesewomen with this degree of weight gain(16). If GWG was already beyond this be-fore the start of the intervention or GWGexceeded 5 kg, women were supportedto minimize their GWG thereafter. Thecoaches had scales available to assistwomen with their weight managementwhen scaleswerenot available in thehome.

AssessmentsAt the three OGTT sessions (Supplemen-tary Fig. 1), after a 10-h fast, womencompleted questionnaires (including,e.g., demographics, prepregnancy weight,lifestyle, past/current medical andobstetric history, and medication use)and anthropometric measurements be-tween blood tests. Local laboratorieswere used to rapidly obtain results ofthe OGTT to assess eligibility for thestudy. Blood samples were centrifuged,and separated serum and plasma ali-quots (1,000 or 250 mL) were placed inmicrorack tubes and stored at 2208C or2808C until further analysis in the cen-tral trial laboratory in Graz, Austria, cer-tified according to ISO 9001 standards.Glucose was measured using the

hexokinase method (DiaSys Diagnostic

Systems, Holzheim, Germany) with alower limit of sensitivity of 0.1 mmol/L.Insulin was quantified by a sandwich im-munoassay (ADVIA Centaur; SiemensHealthcare Diagnostics Inc., Vienna,Austria) with an analytical sensitivity of0.5 mU/L, intra-assay coefficients of var-iation (CVs) of 3.3–4.6%, and interassayCVs of 2.6–5.9%. Leptin was measuredusing a sandwich ELISA (DRG Instru-ments, Marburg, Germany). The assayhad an analytical sensitivity of 1.0 ng/mL,intra-assay CVs of 6.0–7.0%, and interas-say CVs of 8.7–11.6%. All assayswere per-formed according to the instructions ofthe manufacturer. HOMA was calculatedas [glucose z insulin]/22.5 (9).

Height was measured at baselinewith a stadiometer (SECA 206; SECA,Birmingham, U.K.; Leicester Height Mea-sure), and the average value of twomeasurements was used. Women wereweighed on calibrated electronic scales(SECA 888 and SECA 877) wearing noshoes and light clothes, to the nearest0.1 kg; the average value of two mea-surements was used. Weight gain wasdefined as the change in objectivelymeasured weight and was calculatedfor three periods: baseline to 24–28weeks, baseline to 35–37 weeks, and24–28 to 35–37 weeks. Data from themedical records were obtained regard-ing comorbidities, obstetric and perina-tal outcomes, and birth weight.

OutcomesAs primary outcomes, GWG, fasting glu-cose, and insulin sensitivity (HOMA) at35–37 weeks were used as they will bein the main trial. Secondary outcomes

were the number of women who devel-oped GDM, birth weight, insulin concen-tration, and leptin concentration.

StatisticsTrial data were entered into a bespokeweb-based electronic database using theMicrosoft.NET development environ-ment. For the assessment at 35–37weeks, fasting glucose and insulin and in-sulin sensitivity were carried forwardfrom24–28weeks if GDMwas diagnosed.WomendiagnosedwithGDMat 24weeks(n=44)wereexcluded fromthe35–37-weekGWG analyses. Insulin and HOMA datawere log transformed because ofskewness. As a pilot, no power calcula-tions were performed to decide on sam-ple size, and it was arbitrarily agreed thatfour women would be recruited per in-tervention per site to test local proce-dures while minimizing pilot size.

Data were analyzed according to theintention-to-treat principle. Analyses wereperformed blind to the intervention groupallocation. Analyses for the RCT were per-formed according to an a priori statisticalanalysis plan, and hence no adjustmentwas made to significance levels for multi-ple comparisons. Differences between to-tal study sample and number of subjectsdropping out of the study were assessedusing Student t test (normally distributedcontinuous variables), Mann-Whitney Utest (skewed continuous variables), orx2 test (categorical variables). To assess dif-ferences between intervention groups,multilevel analyses were performed, withtwo levels (coach and individual). Thistakes into account possible clustering ef-fects, since the success of treatment canbe dependent on the skills of the provideras well as specific characteristics of atreatment center. Analyseswere adjustedfor baseline values of the outcome or forBMI at baseline for the analyses withGWG outcomes. In the regression anal-yses, all three intervention groups wereentered simultaneously to calculatediffer-ences between groups. In the multilevelmodels, log-transformed data for insulinand HOMA were used. For dichoto-mous variables, logistic regressionmodels were used to assess differen-ces between intervention groups. A bi-lateral P, 0.05 was taken as significant.

RESULTS

Figure 1 shows the flow of the partici-pants throughout the study. A large

Table 1—Lifestyle messages used

PA intervention1) “Be active every day”: Incorporate light and moderate PA as much as possible into daily

life (e.g., by parking further away from destination or undertaking special activities forpregnant women).

2) “Sit less”: Reduce sedentary time.3) “Build your strength”: Incorporate upper and/or lower limb resistance exercise as PA.4) “Take more steps”: Increase the number of steps taken per day.5) “Be more active at weekends”: Be more active during the weekends.

HE intervention1) “Replace sugary drinks”: Reduce intake of sugary drinks (e.g., replace with water).2) “Eat more nonstarchy vegetables”: Eat more nonstarchy vegetables.3) “Increase fiber consumption”: Choose high-fiber over low-fiber products ($5 g fiber/100 g).4) “Watch portion size”: Be conscious about the amount of food eaten each meal.5) “Eat protein”: Increase intake of proteins (e.g., meat, fish, beans).6) “Reduce fat intake”: Reduce fat intake (e.g., snack, fast food, fried foods).7) “Eat less carbohydrates”: Reduce intake of carbohydrates (e.g., potatoes, pasta, rice,

snacks, candy).

1652 DALI Lifestyle Pilot Diabetes Care Volume 38, September 2015

proportion (22%) had GDM on the initialOGTT and hence were not included inthe RCT. The numbers in each groupand their baseline characteristics weresimilar (Table 2). Women dropping out(35; 23%) before the final OGTT hadhigher post-OGTT load glucose and insu-lin concentrations and BMI at baseline(Table 2). Numbers per site rangedfrom 3 in Odense to 26 in Belgium. Sevenof the 150 women showed a weight gainof 5 kg or more between reported pre-pregnancy weight and baseline mea-surements, but many women wereeither unaware of or likely approximatedtheir prepregnancy weight.On average, women gained 8.6 kg (SD

4.6) from baseline to 35–37 weeks ofgestation, and only 20% of womenachieved the ,5 kg GWG target frombaseline across the three interventiongroups. HE alone was associated withless weight gain by 24–28 weeks and35–37 weeks than PA (–2.6 kg [95% CI24.9, 20.2] and 21.6 kg [23.0, 20.2],respectively) (Table 3). No differenceswere observed between HE+PA andthe other two groups.There were no significant differences

in glucose, insulin, or leptinmeasurementsacross groups at baseline or by 24–28weeks’ gestation (Table 3). However, by35–37 weeks’ gestation, HE had signifi-cantly lower fasting glucose and 2-h insulinconcentrationswith nonsignificantly lower

GDM incidence than PA. No significant dif-ferences between HE+PA and the othertwo groups were observed. There wereno significant differences in HOMA or lep-tin (Table 3). At 24–28 weeks, 24 of 130women (19%) had developed GDM, andby 35–37 weeks, this increased to 36 of112 women (32%), of whom 3 receivedinsulin treatment.

CONCLUSIONS

Procedures generally worked well (8),although recruitment overshot (to 150women) due to the lag between base-line data collection, receiving OGTTresults/confirming eligibility, and in-forming all sites that recruitment wascompleted. There was no expectationthat the study would be large enoughto show a difference in the primary out-comes comparing different interven-tions. The significant differences inGWG, fasting glucose, and 2-h insulinlevels (albeit trivial) between HE andPA were therefore surprising, althougheven with the DALI interventions, 32%of women developed GDM. The datasuggest that the HE intervention wasmore efficacious than the PA interven-tion in reducing GDM risk, although thehigher GWG in PA may reflect an in-crease in muscle mass, not necessarilyin adiposity.

Previous RCTs initiated before 20weeks’ gestation have largely shown no

impact on GDM prevalence, fasting glu-cose (3–6,17), or insulin concentrations.Exceptions are the BAMBINO PA inter-vention pilot, which saw a reduction infasting glucose by 28 weeks’ gestation,but with GWG unreported (18), and theLifestyle in Pregnancy (LiP) study, whichshowed lower insulin concentrations at28–30 weeks with the intervention, butno significant reduction in fasting glu-cose (19).

The LiP study showed a GWG differ-ence of only 1.4 kg between interven-tion and control women despite a veryambitious intervention program, in-cluding repeat visits to a dietitian,a weekly fitness class, and fitness cen-ter membership. Thus, a time-consumingprogram might be less effective than asimple one. One of the key issues withlifestyle interventions in general hasbeen their limited impact on GWGwhen compared with control subjects.Several of the RCTs did have lowerGWG in the intervention group (4–6),but control subjects had a lower GWGthan anticipated, resulting in a lesserdifference between the groups. A meta-analysis showed that differences be-tween intervention and control groupsacross 10 RCTs achieved a mean differ-ence in GWG of 22.21 kg (3). In spiteof this, few reported a significant re-duction in glycemia or GDM. The studyby Quinlivan et al. (20) (n = 124) wasthe only trial in the meta-analysisthat achieved a significant reductionin GDM (odds ratio [OR] 0.18) andachieved a 6.80-kg GWG difference.The study by Thornton et al. (21)(n = 232) also achieved a substantiallylower GWG (29.07 kg) but with anonsignificant reduction in GDM(OR 0.53).

Our findings of more/better effectsof diet alone are in line with a previousreview, finding larger effects of dietaryintervention alone on GWG, comparedwith PA or a combined approach (22).We speculate that a combined inter-vention might dilute the message orrequire too much change and then bedemotivating. Another interpretationwould be that a combined interventiondoes not mean “complete” but “partial”HE and PA; PA intervention being lesseffective, HE+PA ranks intermediatebetween HE and PA. The lack of effectof the PA interventions does not im-ply no effect of PA on pregnancy

Figure 1—Consolidated Standards of Reporting Trials (CONSORT) diagram of recruitment, ran-domization, and dropout.

care.diabetesjournals.org Simmons and Associates 1653

and offspring outcomes per se, as thispilot had no control subjects. Interven-tions to increase PA in pregnancy arewell known to be difficult (23), especiallyin the third trimester. Although we arebeing as careful as possible to avoid thekinds of GWG convergence seen in someother major RCTs, it might be difficult toprevent a low GWG in the control groupamong women motivated to come into alifestyle trial. Including multiple Europeancultures might generate a range of life-style responses in control subjects aswell as intervention participants. Suchdifferences between sites, with theirvery different underlying cultural land-scapes (and climates) and associated dif-ferences in nutrition and PA habits, willbe of interest in the main trial. At thispoint, it would appear that our genericapproach to the lifestyle change mes-sages (Table 1) has been successful.These were originally based on an inter-vention among New Zealand Maori (11)and hence expected to be cross cultural

to some extent. We found the motiva-tional interviewing approach to be wellsuited to the intervention. Even so, only29% of participants achieved the ,5 kgGWG goal even in the HE group of thepilot, a proportion comparable to thosein other RCTs (4).

One other difference in the DALI ap-proach from other RCTs is the exclusionof women with GDM by WHO 2013 cri-teria (22%) prior to recruitment. It maybe that in the other trials, it was neverpossible to reverse pre-existing GDM inthese women. However, there is debateover the validity of the new criteria inearly pregnancy (10), which were builtaround data at 24–28 weeks’ gestation(1). Data from China suggest that a sig-nificant proportion of womenwith GDMon the fasting glucose in early pregnancyhave no GDM using the new criteria at24–28 weeks (24).

The studyhas a number ofweaknesses.It was established as a pilot to a full RCT of440 women, and hence there were no

power calculations performed to decideon the number of participants requiredand there was no untreated controlgroup. As a pilot, the expertise of the in-tervention coaches would have improvedover time, in preparation for the main tri-al. Numberswere still too small to look foradherence to lifestyle change or adversepregnancy outcomes. The main trial willreport on accelerometer and food diarydata. We have not adjusted the signifi-cance level for multiple comparisons;however, the comparisons followedour a priori statistical analysis plan, andthe difference in GWG is in linewith otherRCTs, which speaks against the role ofchance.

In conclusion, an HE interventionamong obese European women led tolower GWG, fasting glucose, and 2-h in-sulin concentrations by 35–37 weeks’gestation than a PA intervention or acombination of the two. Although a largertrial is still clearly needed, these pilot find-ings are promising and support the use of

Table 2—Baseline characteristics of all women included in the DALI lifestyle pilot per intervention group and those whodropped out at 35–37 weeks’ gestation

HE, n = 50 HE+PA, n = 50 PA, n = 50 Total, n = 150

Drop out35–37 weeks,n = 35 (23.3%)

P drop out vs.continuing

Age (years) 31.1 6 6.0 30.5 6 5.0 33.1 6 5.2 31.6 6 5.5 32.3 6 5.8 0.37

Multiparous (%) 41.7% 46.0% 46.0% 44.6% 48.6% 0.70

European descent (%) 84.0% 88.0% 90.0% 87.3% 88.6% 1.00

Lives with partner (%) 90.0% 98.0% 87.8% 91.9% 80.0% 0.007

Higher education (%) 44.0% 64.0% 52.0% 53.3% 37.1% 0.03

Maternal smoking (%) 12.0% 22.0% 14.0% 16.0% 22.9% 0.29

Paternal smoking (%) 32.0% 38.0% 38.0% 36.0% 34.3% 0.84

History of GDM (%) 3.2% 3.4% 10.3% 5.6% 9.1% 0.59

First-degree family historyof diabetes (%) 28.0% 26.0% 24.0% 26.0% 28.6% 0.83

Chronic hypertension (%) 14.3% 10.0% 14.0% 12.8% 14.3% 0.78

Gestation on entry (weeks) 14.2 6 1.7 14.2 6 2.0 14.7 6 2.3 14.4 6 2.0 13.9 6 2.2 0.15

Prepregnancy weight (kg) 95.3 6 17.1 93.2 6 15.2 94.1 6 14.6 94.2 6 15.6 94.5 6 17.0 0.89

Weight at entry (kg) 96.4 6 17.0 93.9 6 14.8 96.6 6 14.9 95.7 6 15.5 96.0 6 16.9 0.87

Height (cm) 166.5 6 6.4 165.8 6 6.8 167.2 6 7.5 166.5 6 6.9 163.0 6 6.2 <0.001

BMI pp (kg/m2) 34.3 6 5.6 33.9 6 4.6 33.6 6 4.4 33.9 6 4.9 35.5 6 5.3 0.03

BMI at entry (kg/m2) 34.8 6 5.9 34.1 6 4.7 34.5 6 4.5 34.5 6 5.0 36.0 6 5.2 0.04

Fasting glucose (mmol/L) 4.4 6 0.4 4.6 6 0.6 4.5 6 0.4 4.5 6 0.5 4.6 6 0.3 0.11

1-h glucose (mmol/L) 6.3 6 1.7 6.5 6 1.3 6.5 6 1.5 6.4 6 1.5 7.1 6 1.2 0.01

2-h glucose (mmol/L) 5.5 6 1.2 5.7 6 1.3 5.5 6 1.1 5.6 6 1.2 6.2 6 1.3 0.001

Fasting insulin (mU/L) 14.1 (10.5, 18.2) 12.2 (8.1, 17.9) 14.0 (10.3, 16.6) 13.5 (9.2, 17.8) 12.7 (8.9, 21.6) 0.76

1-h insulin (mU/L) 85.9 (57.8, 156.3) 100.0 (73.3, 154.3) 66.6 (55.7, 120.0) 82.6 (61.5, 150.4) 108.9 (80.9, 174.6) 0.003

2-h insulin (mU/L) 60.3 (36.0, 121.1) 61.0 (40.5, 129.7) 49.3 (32.8, 83.7) 59.5 (36.7, 107.1) 125.8 (60.6, 174.8) <0.001

HOMA 2.76 (1.81, 3.66) 2.26 (1.56, 3.72) 2.75 (1.87, 3.50) 2.65 (1.76, 3.60) 2.49 (1.79, 4.40) 0.58

Leptin (ng/mL) 42.4 6 18.5 42.8 6 17.7 38.9 6 18.1 41.5 6 18.0 46.4 6 18.0 0.11

Data are mean6 SD or median (interquartile range) unless otherwise indicated. No baseline differences were found between intervention groups.The boldface data indicate statistically significant differences. Differences tested with Mann-Whitney U test.

1654 DALI Lifestyle Pilot Diabetes Care Volume 38, September 2015

Table

3—Matern

aloutco

mesin

theDALIlife

style

pilo

tthreeinterve

ntio

ngro

ups

nHE

nHE+PA

nPA

Adjusted

differen

ceorOR(95%

CI)

HEvs.

HE+PA

P

Adjusted

differen

ceorOR(95%

CI)

HEvs.

PAP

Adjusted

differen

ceorOR(95%

CI)

HE+PA

vs.PA

P

Glucose

metab

olism

24–28

weeks

Fastingglu

cose

(mmol/L)

404.3

60.3

424.4

60.4

414.5

60.4

20.001

(201,0.1)

0.9920.1

(20.2,0.1)

0.2020.1

(20.3,0.03)

0.131-h

glucose

(mmol/L)

377.2

61.6

397.2

61.4

397.6

61.7

0.2(2

0.4,0.9)0.43

20.1

(20.8,0.5)

0.6920.5

(21.1,0.2)

0.172-h

glucose

(mmol/L)

365.6

61.3

396.1

61.5

406.1

61.3

20.3

(20.9,0.3)

0.3720.5

(21.0,0.1)

0.1020.2

(20.7,0.4)

0.53Fastin

ginsulin

(mU/L)

4017.9

(12.0,20.6)42

13.1(10.9,20.2)

4315.4

(11.9,19.7)0.05

(20.1,0.2)

0.600.004

(20.2,0.2)

0.9720.04

(20.2,0.1)

0.661-h

insulin

(mU/L)

36157.6

(97.2,194.7)40

139.0(74.7,185.8)

41117.4

(79.7,183.2)0.1

(20.2,0.4)

0.390.1

(20.2,0.3)

0.4720.1

(20.3,0.2)

0.532-h

insulin

(mU/L)

3566.0

(49.1,132.6)40

91.0(44.7,144.6)

4292.2

(51.1,136.8)20.1

(20.4,0.3)

0.7020.2

(20.6,0.1)

0.1720.2

(20.5,0.2)

0.32HOMA

403.30

(2.25,4.08)42

2.63(2.18,3.65)

412.98

(2.11,4.28)20.01

(20.9,0.9)

0.9820.4

(21.4,0.5)

0.3620.4

(21.4,0.5)

0.38Lep

tin(ng/m

L)40

42.76

20.442

39.76

17.941

41.56

17.31.5

(24.8,7.9)

0.6321.6

(27.8,4.7)

0.6223.2

(29.4,3.1)

0.32

Glucose

metab

olism

35–37

weeks

Fastingglu

cose*

(mmol/L)

374.3

60.4

394.4

60.5

424.6

60.4

20.2

(20.3,0.03)

0.0920.3

(20.4,2

0.1)0.01

20.2

(20.3,0.05)

0.161-h

glucose*

(mmol/L)

337.9

61.4

377.8

61.5

388.1

61.6

0.4(2

0.3,1.0)0.28

0.1(2

0.6,0.8)0.79

20.3

(21.0,0.4)

0.412-h

glucose*

(mmol/L)

316.3

61.5

366.7

61.3

386.7

61.0

20.3

(21.0,0.4)

0.3520.6

(21.2,0.01)

0.0620.3

(20.9,0.3)

0.39Fastin

ginsulin*(m

U/L)

3821.8

(14.8,28.4)37

17.9(14.5,27.4)

4018.1

(14.7,24.2)0.1

(20.2,0.4)

0.470.01

(20.3,0.3)

0.9520.1

(20.4,0.2)

0.471-h

insulin*(m

U/L)

33177.6

(115.3,269.1)37

192.5(136.3,220.9)

39175.4

(119.9,230.0)0.1

(20.3,0.4)

0.710.1

(20.2,0.5)

0.470.03

(20.3,0.4)

0.872-h

insulin*(m

U/L)

31115.2

(56.5,187.7)36

152.3(99.6,207.2)

39156.4

(100.0,206.6)20.2

(20.7,0.2)

0.3320.4

(20.8,

20.02)

0.0420.2

(20.5,0.2)

0.37HOMA*

363.90

(2.73,5.54)37

3.44(2.80,5.57)

403.60

(2.29,5.25)20.7

(23.0,1.7)

0.6022.3

(25.6,1.0)

0.1721.8

(25.1,1.5)

0.29Lep

tin(ng/m

L)36

43.76

22.337

42.36

15.040

43.56

17.22.0

(26.6,10.7)

0.6422.6

(210.3,5.2)

0.5124.5

(212.4,3.4)

0.26GDM

at35

–37weeks

(%)

3610

(28%)

3511

(31%)

4115

(42%)

0.84(0.30,2.33)

0.740.67

(0.25,1.75)0.41

0.79(0.31,2.07)

0.64

Weigh

tgain

Weigh

tgain

T1–T2**

(kg)42

3.56

3.942

4.36

3.546

5.26

3.120.8

(22.4,0.7)

0.2922.6

(24.9,2

0.2)0.03

20.7

(23.0,1.6)

0.55Weigh

tgain

T1–T3**,§

(kg)31

7.66

5.330

8.56

4.234

9.66

4.321.0

(23.4,1.4)

0.3921.6

(23.0, 2

0.2)0.02

20.8

(22.3,0.6)

0.24Weigh

tgain

T2–T3**,§

(kg)31

3.96

2.730

3.96

2.034

4.56

2.820.1

(21.4,1.1)

0.8520.5

(21.7,0.87)

0.4320.2

(21.5,1.0)

0.72Weigh

tgain

,5kg**,§

(%)

319(29%

)30

4(13%

)34

6(18%

)2.98

(0.87,10.20)0.08

1.86(0.63,5.52)

0.260.59

(0.17,2.03)0.40

Data

aremean

6SD

ormed

ian(in

terquartile

range)

unless

otherw

iseindicated

.Forcontin

uousoutco

mevariab

les:adjusted

differen

cesfro

mmixed

models,w

ithtw

olevels

(coach

andindivid

ual),ad

justed

for

baselin

evalu

esoftheoutco

me.Fo

rdich

otomousoutco

mevariab

les:logistic

regressionmodels,ad

justed

forbaselin

evalu

esoftheoutco

me.N

aturallo

g-transfo

rmed

values

ofinsulin

were

used

inthemixed

models.N

umbers

ineach

columnvary

with

completen

essofd

ata.Theboldface

data

indicate

statisticallysign

ifican

tdifferen

ces.*Valu

eof24

–28weeks

carriedforw

ardto

35–37

weeks

forwomen

whohad

GDM

at24

–28weeks.**A

djusted

forBMIat

baselin

eandnumber

ofw

eeksbetw

eenmeasu

remen

ts:T1–T2

isweigh

tgain

betw

eenbaselin

eand24

–28weeks;T1

–T3isweigh

tgain

betw

eenbaselin

eand35

–37weeks;

T2–T3

isweigh

tgain

betw

een24

–28weeks

and35

–37weeks.

§Women

with

GDM

at24

–28weeks

excluded

from

analyses.

care.diabetesjournals.org Simmons and Associates 1655

early HE interventions in obese pregnantwomen.

Acknowledgments. The authors thank thecoaches, research midwives and nurses, women,and health professionals collaborating in therecruitment for this study.Funding. This project has received fundingfrom the European Community’s 7th Frame-work Programme (FP7/2007-2013) under grantagreement 242187. In the Netherlands, addi-tional funding was provided by the NetherlandsOrganisation for Health Research and Develop-ment (ZonMw) (grant 200310013). In the U.K.,the DALI team acknowledges the support re-ceived from the NIHR Clinical Research Net-work: Eastern, especially the local diabetesclinical and research teams based in Cambridge.In Spain, additional funding was provided byCAIBER 1527-B-226.

The funders had no role in any aspect of thestudy beyond funding.Duality of Interest.D.M.J. is part of an advisoryboard for research meetings arranged by NovoNordisk. No other potential conflicts of interestrelevant to this article were reported.Author Contributions. D.S. contributed to theconception and design of the trial, wrote theinitial draft of the paper, read and correcteddraft versions of the manuscript, and approvedthe final manuscript. J.G.M.J. performed theanalyses, read and corrected draft versions ofthe manuscript, and approved the final manu-script. S.G., G.J., and J.H. read and correcteddraft versions of the manuscript and approvedthe final manuscript. R.D., A.v.A., R.C., J.M.A.,F.D., G.D., A.K.-W., P.D., E.R.M., D.M.J., L.L.A.,A.L., M.D., A.B., E.W.-O., A.Z., D.H., P.R., and F.J.S.contributed to the conception and design ofthe trial, read and corrected draft versions of themanuscript, and approved the final manuscript.M.N.M.v.P. contributed to the conception anddesign of the trial, performed the analyses, readand corrected draft versions of the manuscript,and approved the final manuscript. D.S. is theguarantor of this work and, as such, had fullaccess to all the data in the study and takesresponsibility for the integrity of the data andthe accuracy of the data analysis.Prior Presentation. Parts of this study werepresented in abstract form at the 75th ScientificSessions of the American Diabetes Association,Boston, MA, 5–9 June 2015.

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1656 DALI Lifestyle Pilot Diabetes Care Volume 38, September 2015