Dietary Intervention in Patients Luciana ... - Diabetes Care · With Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Clinical Trials on Maternal

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Dietary Intervention in PatientsWith Gestational DiabetesMellitus: A Systematic Review andMeta-analysis of RandomizedClinical Trials on Maternal andNewborn OutcomesDiabetes Care 2014;37:3345–3355 | DOI: 10.2337/dc14-1530

OBJECTIVE

Diet is the cornerstone treatment of patients with gestational diabetes mellitus(GDM), but its role in maternal and newborn outcomes has been scarcely studied.The purpose of this study was to analyze the efficacy of dietary interventions onmaternal or newborn outcomes in patients with GDM.

RESEARCH DESIGN AND METHODS

A systematic review and meta-analysis of randomized clinical trials (RCTs) of di-etary intervention in GDM or pregnancy with hyperglycemia was performed.MEDLINE, Embase, ClinicalTrials.gov, Cochrane, and Scopus were searchedthrough to March 2014. The main evaluated maternal outcomes were proportionof patients using insulin and proportion of cesarean delivery; the newborn out-comes were proportion of macrosomia and hypoglycemia and newborn weight.

RESULTS

From 1,170 studies, nine RCTs, including 884 women aged 31.5 years (28.7–33.2)with 27.4 weeks (24.1–30.3) of gestation, were eligible. We divided the RCTsaccording to the type of dietary intervention: low glycemic index (GI) (n = 4; 257patients), total energy restriction (n = 2; 425 patients), low carbohydrates (n = 2;182 patients), and others (n = 1; 20 patients). Diet with low GI reduced the pro-portion of patients who used insulin (relative risk 0.767 [95% CI 0.597, 0.986];P = 0.039) and the newborn birth weight (weight mean differences2161.9 g [95%CI2246.4,277.4]; P = 0.000) as compared with control diet. Total restriction andlow carbohydrate diets did not change either maternal or newborn outcomes.

CONCLUSIONS

A low GI diet was associated with less frequent insulin use and lower birth weightthan control diets, suggesting that it is the most appropriate dietary interventionto be prescribed to patients with GDM.

Division of Endocrinology, Hospital de Clınicas dePorto Alegre, Universidade Federal do RioGrande do Sul, Porto Alegre, Brazil

Corresponding author: Luciana Verçoza Viana,[email protected].

Received 23 June 2014 and accepted 21 August2014.

This article contains Supplementary Data onlineat http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc14-1530/-/DC1.

© 2014 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.

Luciana Verçoza Viana, Jorge Luiz Gross,

and Mirela Jobim Azevedo

Diabetes Care Volume 37, December 2014 3345

META

-ANALYSIS

Page 2

Gestational diabetes mellitus (GDM), de-fined as hyperglycemia diagnosed atpregnancy, has been associated withmany adverse maternal and newbornoutcomes (1), especially increased num-ber of cesarean deliveries, newbornslarge for gestational age, andmacrosomia(2). According to diagnostic criteria (3),the prevalence of GDM ranges from 1.7to 11.6% (4,5). The prevalence of GDMcould be as high as 18% in some regionsif the criteria of the International Associ-ation of Diabetes and Pregnancy StudyGroups Consensus Panel are used (6).Recent systematic reviews (7,8) rein-

force that the treatment of GDM is ef-fective in reducing specific adversematernal and newborn outcomes with-out evidence of short-term harm (7). Di-etary intervention was simultaneouslyevaluated with the use of insulin asneeded in both systematic reviews. Al-though dietary therapy is consideredthe cornerstone treatment for GDM,data on diet intervention as the soleGDM treatment are limited and its ac-tual role in maternal and newborn out-comes has scarcely been studied (9).Moreover, in clinical practice, most ofthe dietary recommendations for pa-tients with GDM have been basedmainly on glucose control, through glu-cose monitoring data, instead of beingbased on data from hard maternal ornewborn outcomes (10,11).The recent recommendations of the

guidelines of the Endocrine Society fordiabetes and pregnancy to attain de-sired glycemic goals are based on thereduction of carbohydrate intake onlyto reach 35–45% of total daily energywith or without calorie restriction (11).Other dietary aspects, such as modifica-tion of the proportion and quality of di-etary macronutrients, were not takeninto account, although there is some ev-idence of beneficial effect of these inter-ventions in both maternal and newbornoutcomes (12–17). Therefore, the aim ofthis study was to analyze the efficacy ofdietary intervention in patients withGDM in maternal and newborn out-comes by systematic review withmeta-analysis of randomized clinical tri-als (RCTs).

RESEARCH DESIGN AND METHODS

This systematic review was carriedout using a protocol constructed ac-cording to the Cochrane Handbook

recommendations (18) and reported inaccordance with the Preferred ReportingItems for Systematic Reviews and Meta-Analyses (PRISMA) statement (19).

Data Sources and SearchesWe searched databases from MEDLINE,Embase, ClinicalTrials.gov register, Co-chrane, and Scopus to identify RCTsthat reported dietary intervention andhyperglycemia in pregnancy or GDMand reported maternal and newbornoutcomes, through March 2014. In ad-dition, we also searched all publishedabstracts from the American DiabetesAssociation (ADA) and European Associ-ation for the Study of Diabetes annualmeetings for the last 5 years.

The initial search comprised theMeSH terms “Diet” [MeSH], “Pregnancy”[MeSH], “Diabetes, Gestational” [MeSH],or glucose intolerance and related entryterms associated with a high-sensitivitystrategy for the search of RCTs availableat http://www.sign.ac.uk/methodology/filters.html#random. All potentially eligi-ble studies were considered for review,limited to the English, Spanish, or Portu-guese language. Amanual searchwas alsoperformed in the reference lists of in-cluded articles and from recent reviewsabout the topic (20,21).

Study SelectionWe included RCTs that evaluated the ef-fect of dietary intervention on patientsdiagnosed with GDM or glucose intoler-ance or hyperglycemia during preg-nancy with reported maternal andnewborn outcomes. Dietary interven-tion must have lasted for at least 4weeks and continued until delivery.We excluded studies if they were notrandomized, they included patientswith type 1 or type 2 diabetes, the di-etary intervention was the same in allstudied groups, the dietary characteris-tics were not available, or they did notreport any of the outcomes of interest.

The maternal outcomes evaluatedwere as follows: weight gain, rate of ce-sarean sections, labor induction, gesta-tional age at delivery, and number ofpatients who start using insulin. Thenewborn outcomes were as follows:weight, frequency of newborn withmacrosomia (birth weight .4 kg), largefor gestational age (birth weight .90thcentile), or small for gestationalage (SGA; birth weight ,10th centile),

prematurity, and birth trauma orhypoglycemia.

Data Extraction and QualityAssessmentAll citations retrieved from electronicdatabases were imported to the EndNoteprogram. Two reviewers (M.J.A. and L.V.V.)independently analyzed the titles andabstracts of every paper retrieved fromthe literature search to identify poten-tially eligible studies. All studies thatdid not meet the inclusion criteria wereexcluded. The full text of the remainingpapers was obtained for further exami-nation. Disagreements were solved by athird reviewer (J.L.G.).

The data of included studies were in-dependently extracted by the same tworeviewers using a standardized data ex-traction form. Extracted data includedthe following: first author’s name, yearof publication, number of participants,details of the study design (i.e., random-ization method), trial duration, andpatient characteristics (age, BMI, gesta-tional age at the diagnoses of GDM, andethnicity [white or non-Caucasian]).Diet characteristics (total energy, mac-ronutrients, and fiber content) and eval-uation of dietary compliance wereextracted from intervention and controldiet descriptions. The dietary prescrip-tion or recommendation was extractedand, when available, we chose to pres-ent the actual intake data. Authors werecontacted in order to obtain any rele-vant missing information, and personalcontact allowed us to include additionaldata from two studies (12,14).

We divided the RCTs into four catego-ries according to the type of dietary in-tervention: low glycemic index (GI),total energy restriction, low carbohy-drate content, and others. The GI is anin vivo measure of the blood glucose re-sponse to a standard amount of carbo-hydrate from a food, relative to areference food (glucose or white bread.)The GI value ranks foods on a scale from0 to 100 according to the extent towhich they raise blood glucose after eat-ing. Foods with GI ,55 have been con-sidered low GI foods (22–24). The dailydietary GI is calculated based on thecarbohydrate content per serving ofeach ingested food. Restriction of totalenergy was defined according to ADArecommendations for medical nutri-tion therapy in GDM: modest caloric

3346 Systematic Review of Diet Interventions for GDM Diabetes Care Volume 37, December 2014

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restriction consisting of 1,600–1,800kcal or ;33% reduction in caloric intake(10). Consumption of carbohydratesrepresents 45–65% of total daily caloriesaccording to the dietary reference in-takes for the general population (25);low carbohydrate diet was character-ized by a carbohydrate intake lowerthan 45% of energy, without restrictingthe total energy. The fourth categorywas created to include any study identi-fied in the database search that fulfilledour inclusion criteria of this systematicreview but did not meet traditional di-etary interventions, such as low GI, en-ergy restriction, or low carbohydratediets.In the evaluation of quality assess-

ment, two reviewers (M.J.A. and L.V.V.)independently assessed the methodolog-ical quality of studies. We used a scorebased on the Cochrane Collaborationtool for assessing risk of bias of every in-cluded study andGRADE score (Cochrane,GRADE) for each meta-analysis.According to the Cochrane Collabora-

tion, biases were classified into sixdomains: selection, performance, detec-tion, attrition, reporting, and other(18,26). The “other” chosen domain wasthe assessment of dietary compliance.The risk of bias for each domain wasclassified as high, low, or unclear. Re-garding dietary compliance, the riskwas classified as “low” if the study de-scribed themethod of dietary complianceevaluation.The quality of the body of evidence of

each meta-analysis was assessed by theGRADE approach (27), including factorsthat may decrease (e.g., methodologicalquality, directness of evidence, hetero-geneity, precision of effect estimates,and risk of publication bias) or increase(e.g., large magnitude of effect, reduc-tion or spurious effect due to plausibleconfounding factors, and dose-responsegradient) the quality of evidence. Eachevaluated factor was rated as high,mod-erate, low, or very low (27,28). Usingthis approach, we considered a seriousrisk of bias when an individual study hadmore than three unclear or high risk ofbias, and imprecision was defined as ameta-analysis confidence interval.0.5.

Data Synthesis and AnalysisDescriptive data from the systematic re-view were presented as mean and/orrange, when available. Changes in

continuous data were reported as abso-lute differences between arithmeticmeans at baseline and end of study,and weight mean differences wereused in the analyses. Relative risk (RR)was evaluated for binary data.

The heterogeneity between the stud-ies was evaluated by Cochran Q test,and a P for trend#0.10 was consideredstatistically significant. The I2 test wasalso performed to evaluate the magni-tudeofheterogeneity. Possible publicationbias was assessed using a contour-enhanced funnel plot of each trial’seffect size against the standard error.Funnel plot asymmetry was evaluatedby Begg and Egger tests, and a significantpublication bias was considered if theP value was ,0.10.

All statistical analyses were per-formed using Stata 11.0 software (Stata,College Station, TX). Significance was setat P , 0.05, and 95% CIs are quotedthroughout.

RESULTS

Literature SearchWe identified 1,170 studies in databasesearches (Fig. 1). Of these, 1,121 wereexcluded based on title and abstract,leaving 49 articles for further full textevaluation. Forty of these studies wereexcluded, most of them due to a non-randomized design, not reporting theoutcomes of interest, diet not beingthe primary intervention, being a sub-analysis of a major study, not providingthe dietary characteristics, or if the pa-tients were not followed until delivery.Therefore, we selected nine trials to beincluded in the current systematicreview.

Study CharacteristicsThe characteristics of the nine includedtrials are summarized in Table 1. A totalof 884 pregnant women aged 28.7–33.2years (mean 31.5 years) who had a diag-nosis of GDM between 24.1 and 30.3weeks of pregnancy (mean 27.4 weeks)were included. The diagnosis of GDMwas established by different criteria (29–37) in the RCTs included in this systematicreview (Supplementary Table 1).

The available data from the reviewedRCTs allowed us to perform meta-analyses of low GI, total energy restric-tion, and low carbohydrate diets (Fig. 2).Only one study was included in thefourth category of dietary intervention.

Low GI DietLow GI diet analyses included fourstudies (12–15) and 257 patients, aged32.9 years, in whom the diagnosis ofGDM was established at 26.8 weeks(24.1–30.1). Regarding diet character-istics, mean energy intake was similarin the intervention (1,675 kcal/day,range 1,477–1,834) and control (1,694kcal/day, range 1,485–1,932) groups. TheGI score in the low GI dietary interven-tion ranged from 47 to 49 (mean 48.9),whereas in the control group the rangewas 47 to 58 (mean 53.5). Dietary GI in alltrials was calculated based on food com-position tables and published GI valuesusing the glucose = 100 scale. The dailytotal fiber intake was 27.5 g/day (25.6–30) in the intervention and 23.6 g/day(22.9–25) in the control groups.

Data from low GI trials allowed us toevaluate thematernal weight gain in thelast visit of the study, frequency of ce-sarean section, insulin use, SGA andmacrosomia, and newborn weight. Pa-tients in the low GI diet group used in-sulin less frequently (RR 0.767 [95% CI0.597, 0.986]; P = 0.039), and the new-born weight (MWD 2161.9 g [95% CI2246.4, 277.4]; P = 0.000) was lowerthan those in the control group. How-ever, there was no significant changein maternal weight gain (MWD 20.412kg [21.842, 1.017]; P = 0.428) or cesar-ean section rates (RR 1.045 [0.736,1.483]; P = 0.286) or an increase in thenumber SGA newborns (RR 1.588[0.603, 4.182]; P = 0.349) or with macro-somia (RR 0.479 [0.147, 1.561]; P =0.222). The less frequent use of insulinmeans that 13 out of 100 patients withGDM will not need to use insulin if theyadopt a low GI diet during pregnancy.

No heterogeneity was found for theanalyses of maternal weight gain(I2 = 0%; P = 0.428), cesarean sectionrates (I2 = 20.2%; P = 0.286), insulinuse (I2 = 34.0%; P = 0.208), newbornweight (I2 = 0%; P = 0.404), number ofSGA newborns (I2 = 0%; P = 0.745), andmacrosomia (I2 = 0%; P = 0.967) andalso no publication bias as assessed byfunnel plot and Egger test, except apossible publication bias for macroso-mia analyses (Egger test, P = 0.043)(Supplementary Fig. 1).

Total Energy Restriction DietTotal energy restriction diet analyses in-cluded two RCTs (38,39) with 425

care.diabetesjournals.org Viana, Gross, and Azevedo 3347

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patients aged 30.6 years (30.4–30.7)in whom GDM diagnosis was establishedat between 24 and 30 weeks of preg-nancy. Energy restriction interventionwasa calorie-restricteddiet of 35 kcal/idealbody weight (kg)/day in one of the studies(38). In the other (39), a moderate restric-tion diet representing 70% of recom-mended dietary intake for women withGDM was adopted. This means a reduc-tion of;30% total of energy intake.In the total energy restriction cate-

gory, data for cesarean rates, frequencyof macrosomia, and neonatal hypogly-cemia were available. Incomplete dataabout other newborn outcomes andmaternal weight prevented us from fur-ther analyses. Total energy restrictionintervention did not increase the num-ber of cesarean sections (RR 1.091 [95%CI 0.769, 1.496]; P = 0.588), frequency ofmacrosomia (1.002 [0.649, 1.547];

P = 0.992), or neonatal hypoglycemia(1.014 [0.718, 1.434]; P = 0.936).

High heterogeneity in the studies wasobserved for rates of both cesarean sec-tion (I2 = 73.7%; P = 0.051) and neonatalhypoglycemia (I2 = 75.3%; P = 0.045)without publication bias as assessed byfunnel plot. For the analyses of fre-quency of macrosomia, there was noheterogeneity (I2 = 26%; P = 0.245) orpublication bias by funnel plot. Eggertests were not calculated due to thesmall number of included studies (Sup-plementary Table 1).

Low Carbohydrate DietTwo studies of low carbohydrate diet(16,17) evaluated 182 patients aged30.8 years (28.7–32.8) at 29.8 weeks(29.2–30.3) of pregnancy at GDMdiagnoses. Total daily energy from car-bohydrates ranged from 40 to 45% in

the intervention group and from 55 to60% in the control groups.

No difference was found regardingcesarean section rates (RR 1.182 [95%CI 0.764, 1.829]; P = 0.588) and fre-quency of insulin use (1.061 [0.796,1.415]; P = 0.685) and macrosomia(0.346 [0.063, 1.912]; P = 0.992) in thelow carbohydrate diet. Data on mater-nal weight gain and newborn outcomeswere incomplete in those studies.

No heterogeneity was found in theanalyses of the rate of cesarean section(I2 = 0%; P = 0.619) and the frequency ofinsulin use (I2 = 57.7%; P = 0.124) andmacrosomia (I2 = 0%; P = 0.590). How-ever, visual asymmetry was present forthe frequency of insulin use and macro-somia as evaluated by funnel plot. Eggertests were not calculated due to the smallnumber of included studies (Supplemen-tary Fig. 1).

Others: Ethnic DietA small Italian study conducted in 20pregnant women with GDM (40) com-pared an ethnic-based food choice diet(“ethnic meal plan”) with a diet recom-mended by ADA, both with the sameenergy and macronutrient composition.The intervention diets consisted of theadoption of food plans based on six eth-nic groups (Chinese, Filipino, Moroccan,Nigerian, Romanian, and Bangladeshi).Typical dishes from the foreign women’shome country were chosen. The studydid not demonstrate differences in ce-sarean section rates, maternal and fetalweight, insulin use, and macrosomia.

Meta-analyses Quality EvaluationIndividual quality of studies revealed alow risk of bias for most evaluated do-mains, except for concealment allocationin two studies (10,12). Most RCTs de-scribed some type of assessment of dietcompliance (Supplementary Table 2).

The GRADE quality of evidence wasfrom moderate to high for low GImeta-analyses, except for macrosomia.However, we graded the maternalweight gain meta-analyses as low qual-ity. Actually, the individual data forpregnancy weight gain could havebeen inaccurate because this informa-tion could have been collected in differ-ent follow-up periods. GRADE qualitywas low for all evaluated maternal andnewborn outcomes of energy restrictionand low carbohydrate meta-analyses(Supplementary Table 3).

Figure 1—Flow diagram of literature search to identify RCTs evaluating the effect of diet inpatients with GDM.

3348 Systematic Review of Diet Interventions for GDM Diabetes Care Volume 37, December 2014

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Table

1—Characteristicsofthestudiesacc

ord

ingto

dietary

interventionin

GDM

Author,year

Samplecharacteristics

GDM

criteria

Dietcharacteristics

Maternaloutcomes

New

born

outcomes

Dietary

interven

tion:lowGI

Perichart-Perera,

2012

n=48

Age

=33

.26

5.1years

GDM

diagn

oses:

24.126

4.6weeks

BMI=31

.46

4.8kg/m

2

(pregestational)

ADA,20

04

Interven

tion(n

=27

):LG

Idiet*

Energy:1,47

7.46

400.8kcal/day

CHO:49

.36

6.8%;Prot:24

.16

4.5%;

Lip:28

65.8%

GI:47

.56

6.5

GL:NA

Fiber:NA

Interven

tion

Totalw

eigh

tgain:4.16

4.9kg

Cesarean:20

(83.3%

)Laborinduction:NA

Insulin

use:8patients

(30%

)

Interven

tion

Birth

weight:2,95

46

649g

Macrosomia:1

Prem

aturity:3

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:1

Control(n=21

):alltypes

ofCHO*

Energy:1,48

5.46

26.4

kcal/day

CHO:46

.26

6.2%;Prot:24

.46

4.55%

;Lip:30

.86

6.1%

GI:47

.06

9.9

GL:NA

Fiber:NA

Control

Totalw

eigh

tgain:3.36

3.9kg

Cesarean:16

(76.2%

)Laborinduction:NA

Insulin

use:9patients

(43%

)

Control

Birth

weight:3,11

56

469g

Macrosomia:1

Prem

aturity:2

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:1

Grant,20

11n=47

Age

=34

64years

GDM

diagn

oses:

276

2.9weeks

Nonwhite:

85%

BMI=26

.56

4.8kg/m

2

(pregestational)

Can

ada,20

08

Interven

tion(n

=23

):LG

Idiet*

Energy:NA

CHO:NA;Prot:NA;Lip:NA

GI:49

60.8

GL:98

.26

5.1

Fiber:30

61.6g/day

Interven

tion

Weightgain:0.356

0.05

kg/w

eek

Cesarean:NA

Laborinduction:NA

Insulin

use:13

patients

(62%

)

Interven

tion

Birth

weight:3,12

46

124g

Macrosomia:1

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:1

Control(n=24

):interm

ediate/highGIdiet*

Energy:NA

CHO:NA;Prot:NA;Lip:NA

GI:58

60.5

GL:12

56

8.8

Fiber:23

61g/day

Control

Weightgain:0.376

0.07

kg/w

eek

Cesarean:NA

Laborinduction:NA

Insulin

use:12

patients

(55%

)

Control

Birth

weight:33

06

220g

Macrosomia:2

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:0

Moses,20

09n=63

Age

=31

.16

4.2years

GDM

diagn

oses:

30.1

61.1weeks

Nonwhite:

1.6%

BMI=32

.46

7.3kg/m

2

(aten

rollm

ent)

ADIPS

Interven

tion(n

=31

):LG

I*Energy:1,71

36

66kcal/day

CHO:36

.76

1.1%;Prot:23

.96

0.7%;

Lip:33

.46

1.2%

GI:48

.06

0.9

GL:NA

Fiber:25

.66

1.6g/day

Interven

tion

Totalw

eigh

tgain:8.96

5.0kg

Cesarean:5(16%

)Laborinduction:NA

Insulin

use:9patients

(29%

)

Interven

tion

Birth

weight:3,27

96

464.5

gMacrosomia:1

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:2

Con

tinu

edon

p.33

50

care.diabetesjournals.org Viana, Gross, and Azevedo 3349

Page 6

Table

1—Continued

Author,year

Samplecharacteristics

GDM

criteria

Dietcharacteristics

Maternaloutcomes

New

born

outcomes

Control(n=32

):highGIdiet*

Energy:1,66

46

79kcal/day

CHO:37

.86

1.1%;Prot:23

.56

0.8%;

Lip:34

.06

1.8%

GI:56

.06

1.1

GL:NA

Fiber:22

.96

1.1g/day

Control

Totalw

eightgain:10.66

70.0kg

Cesarean:8

(25%

)Laborinduction:NA

Insulin

use:19

patients(59%

)

Control

Birth

weigh

t:3,33

46

431.5

gMacrosomia:2

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:0

Louie,2

011

n=99

Age

=33

.26

4.3years

GDM

diagnoses:

26.1

64.12weeks

Nonwhite:

64.1%

BMI=24

65kg/m

2

(pregestational)

ADIPS

Interven

tion(n

=47

):LG

I;target

GI#50

*Energy:1,83

46

425kcal/day

CHO:39

%;Prot:23

%;Lip:35

%GI:47

61

GL:84

63

Fiber:27

61g/day

Interven

tion

Totalw

eightgain:11

.96

0.7kg

Cesarean:10

(21%

)Laborinduction:NA

Insulin

use:25

patients

(53.2%

)

Interven

tion

Birth

weigh

t:3.36

0.1kg

Macrosomia:1

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:5

Control(n=45

):moderateGIandhighfiber

diet;

target

GI;

60*

Energy:1,93

26

476.3

kcal/day

CHO:40

%;Prot:22

%;Lip:35

%GI:53

61

GL:10

56

4Fiber:25

61g/day

Control

Totalw

eightgain:13

.16

0.9kg

Cesarean:5(11%

)Laborinduction:NA

Insulin

use:29

patients

(65.1)

Control

Birth

weigh

t:3.36

0.1g

Macrosomia:3

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:4

Dietary

interven

tion:totalenergy

restriction

Garner,1

997

n=30

0Age

=30

.76

4.6years

GDM

diagnoses:

24–30

weeks

Hatem

criteria

Interven

tion(n

=14

9):calorie-restricted

diet§

Energy:35

kcal/idealb

odyweigh

t(kg)/day

Interven

tion

Weigh

tgain:12

.54kg

Cesarean:30

(20.1%

)Laborinduction:NA

Insulin

use:36

patients

(24.2%

)

Interven

tion

Birth

weigh

t:3,43

76

575g

Macrosomia:24

(16.1%

)Prem

aturity:NA

Birth

trau

ma:

0Hypoglycem

ia:21

(14.1%

)SG

A:NA

Control(n=15

0):Canad

aFoodGuiderecommen

dations

Control

Weigh

tgain:13

.37kg

Cesarean:28

(18.6%

)Laborinduction:NA

Insulin

use:NA

Control

Birth

weigh

t:3,54

46

601g

Macrosomia:28

(18.7%

)Prem

aturity:NA

Birth

trau

ma:

0Hypoglycem

ia:13

(8.7%)

SGA:NA Con

tinu

edon

p.33

51

3350 Systematic Review of Diet Interventions for GDM Diabetes Care Volume 37, December 2014

Page 7

Table

1—Continued

Author,year

Samplecharacteristics

GDM

criteria

Dietcharacteristics

Maternaloutcomes

New

born

outcomes

Rae,2

000

n=12

5Age

=30

.4years

GDM

diagn

oses:

28.2

65.3weeks

BMI=38

60.7kg/m

2

(aten

rollm

ent)

OGTT

fasting

.10

0mg/dL

and/or2h

.14

5mg/dL

Interven

tion(n

=66

):moderateen

ergy

restriction(30%

):1,59

0–1,77

6kcal*

Energy:1,56

6kcal/day

CHO:42

60.7%

;Prot:25

60.3%;Lip:31

60.7%

Interven

tion

Weigh

tgain:11

.566

10.7

kgCesarean:36

(40%

)Laborinduction:26

(46%

)Insulin

use:11

patients(17.5%)

Interven

tion

Birth

weight:3,46

1g

Macrosomia:11

(16.7%

)Prem

aturity:14

(22.2%)

Birth

trau

ma:

NA

Hypoglycem

ia:25

(37.3%

)SG

A:NA

Control(n=58

):noten

ergy-restricteddiet;

2,01

0–2,22

0kcal*

Energy:1,63

0kcal/day

CHO:41

60.6%

;Prot:24

60.3%;

Lip:34

60.7%

Control

Weigh

tgain:9.68

611

.04kg

Cesarean:19

(33.9%

)Laborinduction:23

(45.2%

)Insulin

use:9patients(16.75

%)

Control

Birth

weight:3,26

7g

Macrosomia:6(10.7%

)Prem

aturity:13

(22.1%)

Birth

trau

ma:

NA

Hypoglycem

ia:29

(50%

)SG

A:NA

Dietary

interven

tion:lowcarbohydrate

Moreno-Castilla,2

013

n=15

2Age

=32

.86

4.1years

GDM

diagn

oses:

30.3

63.3weeks

Nonwhite5%

BMI=26

65.6kg/m

2

(pregestational)

NationalDiabetes

Group

criteria

Interven

tion(n

=75

):lowcarbohydrate

diet(40%

)Energy:.1,80

0kcal/day

CHO:40

%;Prot:20

%;Lip:40

%

Interven

tion

Weigh

tgain:1.46

2kg

Cesarean:25

(33.8%

)Laborinduction:NA

Insulin

use:41

(54.7%

)

Interven

tion

Birth

weight:NA

Macrosomia:1

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:12

Control(n=75

):highcarbohydrate

diet(;

60%)§

Energy:.1,80

0kcal/day

CHO:55

%;Prot:20

%;Lip:25

%

Control

Weigh

tgain:2.36

2.1kg

Cesarean:20

(26.7%

)Laborinduction:NA

Insulin

use:41

(54.7%

)

Control

Birth

weight:NA

Macrosomia:4

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:8

Cypryk,20

07n=30

Age

=28

.76

3.7years

GDM

diagn

oses:

29.2

65.4weeks

Allwhite

WHOcriteria

Interven

tion(n

=15

):lowcarbohydrate

diet(;

45%)§

Energy:NA

CHO:45

%;Prot:25

%;Lip:30

%

Interven

tion

Weigh

tgain:NA

Cesarean:7(47%

)Laborinduction:NA

Insulin

use:2(13%

)

Interven

tion

Birth

weight:3,40

76

309g

Macrosomia:0

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:NA Con

tinu

edon

p.33

52

care.diabetesjournals.org Viana, Gross, and Azevedo 3351

Page 8

CONCLUSIONSThis systematic review of dietary inter-vention in GDM included 884 pregnantwomen from nine RCTs.Wewere able toperform three meta-analyses accordingto the type of dietary interventionsused: low GI, total energy restriction,and low carbohydrate diets. Remark-ably, only the low GI diet was associatedwith beneficial outcomes: less frequentinsulin use and lower newborn weightthan the control dietary interventions,without increasing the number of SGAnewborns and macrosomia. Thesemeta-analyses rated a moderate tohigh quality according to the GRADE pro-file. On the other hand, meta-analysesof energy restriction and low carbohy-drate diets did not influence any of thestudied outcomes.

Diet is the main treatment for GDM,and as far as we know, this is the firstsystematic review with meta-analysesthat shows benefits of a specific dietaryintervention in GDM management.Moreover, we evaluated these benefitsbased on hard outcomes, instead of onresults related to glucose parametersonly.

The last published systematic reviewfrom Cochrane on different dietary ad-vice for women with GDM (20) couldnot find any significant dietary benefit.Unlike our results, the low GI did notinfluence insulin use and birth weight.It is worth noting that most of thoseresults (birth weight, cesarean section,and SGA) were based on only one studyanalysis. Furthermore, as comparedwith ours, the authors included onlyone RCT in type 2 diabetes and GDM(41) and did not include two otherstudies (12,15) in their low GI meta-analyses. Although the results ofenergy restriction and low carbohy-drate diets were similar to ours, theCochrane review included only oneRCT in each of these diet categories.Another recent systematic reviewabout nutritional strategies for womenwith GDM (21) did not perform anymeta-analyses.

The low GI diet was the only con-firmed advantageous dietary interven-tion to be followed during pregnancyby women with GDM. According to ourresults, 13 out of 100 patients with GDMwill not need to use insulin if theyadopt a low GI diet during pregnancyand birth weight was lower but without

Table

1—Continued

Author,year

Samplecharacteristics

GDM

criteria

Dietcharacteristics

Maternaloutcomes

New

born

outcomes

Control(n=15

):highcarbohydrate

diet(;

60%)§

Energy:NA

CHO:60

%;Prot:25

%;Lip:15

%

Control

Weightgain:NA

Cesarean:5(33%

)Laborinduction:NA

Insulin

use:1(7%)

Control

Birth

weigh

t:3,38

56

418g

Macrosomia:2

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:NA

Dietary

interven

tion:others

Valen

tini,20

12n=20

Age

=29

.66

4years

GDM

diagnoses:

24.2

66.9weeks

BMI=24

.96

4.2kg/m

2

(pregestational)

Fourth

International

Workshop

Conference

onGDM

Interven

tion(n

=10

):ethnicmealp

lan§

Energy:1,80

0–2,20

0kcal/day

CHO:55

%;Prot:17

%;Lip:28

%Fiber:21

g/day

Interven

tion

Weightgain:12

.16

4.3kg

Cesarean:6

Laborinduction:NA

Insulin

use:2(20%

)

Interven

tion

Birth

weigh

t:3,06

46

626g

Macrosomia:0

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:1

Control(n=10

):ADArecommen

dations§

Energy:1,80

0–2,20

0kcal/day

CHO:53

%;Prot:18

%;Lip:28

%Fiber:26

g/day

Control

Weightgain:14

.36

6.9kg

Cesarean:5

Laborinduction:NA

Insulin

use:1(10%

)

Control

Birth

weigh

t:3,43

46

649g

Macrosomia:2

Prem

aturity:NA

Birth

trau

ma:

NA

Hypoglycem

ia:NA

SGA:0

ADIPS,Australasian

Diabetes

inPregnan

cySociety;CHO,carbohydrates;GL,glycem

icload

;Lip,lipids;LG

I,lowGI;OGTT,oralglucose

tolerance

test;Prot,protein;W

HO,W

orldHealthOrgan

ization.*Actualintake.

§Dietary

prescription.

3352 Systematic Review of Diet Interventions for GDM Diabetes Care Volume 37, December 2014

Page 9

increasing the SGA rates than the con-trol diets. Beneficial effect on birthweight was already observed in non-GDM pregnant patients after a low GIdiet (42). It has been shown that a lowGI diet improves insulin sensitivity (43)and reduces the insulin requirementpossibly due to its ability to reduce post-prandial glucose excursions (44). Note-worthy, the GI in intervention groups

was really low (47–49), which could bean indirect measure of dietary compli-ance in GDM patients.

Regarding macrosomia and maternalweight, the quality of our meta-analysesprevents us from arriving at a definitiveconclusion about the effect of low GIdiet in these outcomes. This could berelated to a relatively small number ofmacrosomic newborns, both in the

intervention (4/128) and in the con-trol groups (8/122). On the otherhand, in a trial that evaluated the effectof low GI in 800 pregnancies in non-GDMwomen at high risk for macrosomia(45), the adoption of a low GI diet alsodid not reduce fetal macrosomia.There is no reason to assume thatpatients with GDM would behavedifferently.

Figure 2—Forest plots of dietary intervention for patients with GDM: low GI diet (A), energy restriction diet (B), and low carbohydrate diet (C).

care.diabetesjournals.org Viana, Gross, and Azevedo 3353

Page 10

Another promising dietary inter-vention for GDM patients couldbe the Dietary Approaches to StopHypertension (DASH) diet. In a smalltrial, the DASH diet adopted for 4weeks during pregnancy was able toreduce insulin use, cesarean rates,and birth weight in patients withGDM. We did not include that studyin our systematic review because thedietary intervention was not contin-ued until delivery (46). However it isimportant to note that the DASH dietcan be considered a low GI dietary ap-proach. This observation reinforcesthe role of a low GI diet for GDMwomen.A possible limitation of our system-

atic review could be related to differentdiagnostic criteria for GDM used in theincluded studies. However, in oursearch, the terms hyperglycemia andpregnancy were both included. Thisstrategy should have prevented missingany study on abnormal glucose homeo-stasis in pregnancy. This is an importantaspect of our systematic review since itis well known that it is worthwhile totreat even mild glucose abnormalitiesin pregnancy (47). Regarding our mainresult, the low GI diet, a dose-responseanalysis would provide valuable infor-mation. However, a narrow GI interval(47–49) did not allow us to conduct it.Another potential weakness of our sys-tematic review was the small number ofstudies included in each dietary inter-vention category analysis. It would beinteresting to compare all included trialsthrough a network meta-analysis. How-ever, different dietary strategies couldnot be connected and we were unableto perform this analysis. Furthermore, inthe included studies, the outcomes eval-uated were not always the same, werenot uniformly standardized, or wereeven not available. A low GRADE qual-ity score for most performed meta-analyses outcomes (low GI: macrosomiaand maternal weight; energy restrictiondiet: cesarean section, macrosomia, andneonatal hypoglycemia; low carbohy-drate diet: cesarean section, insulinuse, and macrosomia) could explain thelack of difference between interventionand control diets. Finally, the adherenceof dietary interventions was not as-sessed or reported in three trials. Allthese aspects reinforce the need to per-form well-designed RCTs on the effects

of dietary intervention in patients withGDM.

In conclusion, we demonstrated thatin patients with GDM, the use of a lowGIdiet was associated with less frequentinsulin use and lower birth weight thanthe control diets, without any detected ad-verse effects. Therefore, the present avail-able evidence suggests that a lowGI diet isthe most appropriate dietary interventionto be prescribed to patients with GDM.

Funding. This study was supported by Con-selho Nacional de Desenvolvimento Cientıfico eTecnologico, Coordenação de Aperfeiçoamentode Pessoal de Nıvel Superior, and Fundo deIncentivo a Pesquisa Hospital de Clınicas dePorto Alegre.Duality of Interest. No potential conflicts ofinterest relevant to this article were reported.Author Contributions. L.V.V. was engaged inconception and design, data extraction, statis-tical analyses, interpretation of data, and draft-ing of the manuscript. J.L.G. was responsible forconception, design, and critical revision of themanuscript. M.J.A. was responsible for concep-tion, design, data extraction, statistical analyses,interpretation of data, drafting of themanuscript,and administrative and technical support.

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