EAL

GDM: Carbohydrate (2016)

Citation:

Moreno-Castilla C, Hernandez M, Bergua M, Alvarez MC, Arce MA, Rodriguez K, Martinez-Alonso M, Iglesias M, Mateu M, Santos MD, Pacheco LR, Blasco Y, Martin E, Balsells N, Aranda N, Mauricio D. Low-carbohydrate diet for the treatment of gestational diabetes mellitus: a randomized controlled trial. Diabetes Care, 2013. Aug; 36 (8): 2,233-2,238. PMID: 23564917. PubMed ID: 23564917

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

The purpose of this study was to determine if a low CHO diet for the treatment of GDM would lead to a lower rate of insulin treatment with similar pregnancy outcomes compared with a control diet.

Inclusion Criteria:

Women aged 18 years to 45 years (inclusive)
Diagnosis of GDM
Singleton pregnancy
Gestational age no more than 35 weeks.

Exclusion Criteria:

Unwillingness to follow a prescribed diet
Inability to understand the Spanish language
Pregnancy co-morbidites other than obesity, hypertension or dyslipidemia.

Description of Study Protocol:

Recruitment

Subjects were recruited from the diabetes and pregnancy outpatient clinic of the reference hospital of the Public Health System of the province of Lleida Catalonia
All women at their first outpatient appointment were offered participation in the study between November 2008 and July 2011.

Design

The study was a two-arm, open, parallel, randomized controlled trial comparing two dietary interventions (minimum 1,800kcal per day) designed by a team of dietitians to treat GDM
Protein content was similar (20% of total energy intake) but CHO and fat varied. Low CHO diet: CHO, 40% of energy; fat, 40%). Control diet: CHO, 55% of energy; fat, 25%. The diets were divided into three principal meals and three snacks, all with a pre-specified number of CHO servings. No changes in the CHO distribution were allowed while the patient was under dietary therapy alone. Once insulin was started, changes in the CHO distribution could be made to optimize insulin treatment because the patients had already reached the primary outcome of the study.
The following data were assessed and recorded at each follow-up visit: Weight, blood pressure, number of SMBG results outside the target values, insulin dose and ketonuria
The pre-delivery weight was the last weight registered in the medical record during any of the four weeks preceding delivery
All of the deliveries took place in our hospital
Pregnancy complications, ultrasound follow-up data and pregnancy outcomes, including newborn weight and length adjusted for gestational age, occurrence of newborn hypoglycemia (glycemia, 2.2mmol per L), and the type of delivery were obtained from the electronic medical record system
Gestational age was calculated based on the last menstrual period and corrected, if indicated, by an early ultrasound scan. Newborns were categorized into small-for-gestational age (birth weight, 10th centile), normal, or large-for-gestational-age (LGA; birth weight above the 90th centile), using the Spanish tables of neonatal weight adjusted for sex and gestational age.
Macrosomia was defined as birth weight of at least four kg.

Blinding Used

One nutritionist was blinded to the patient group allocation and docmented the food records in a separate database
A biostatistician blinded to the diet allocation of the participants performed the statistical analyses.

Intervention

The intervention consisted of a low CHO diet compared to a controlled diet. Protein content was similar (20% of total energy intake) but CHO and fat varied. Low CHO diet: CHO, 40% of energy; fat, 40%. Control diet: CHO, 55% of energy; fat, 25%).
CHO intake was evaluated using the estimated food record method over three non-consecutive days, including a weekend or a holiday
The subjects were asked to record their initial intake of foods containing CHO with this method. The first dietary assessment was made after the initial study diet prescription and a second assessment occurred after the following appointment, at which the dietary plan for the patient was revised for adherence. This method was used for its technical simplicity and cost.
A book with graphic representations of food portions was used at the dietary interviews

Statistical Analysis

The Fisher exact test was applied to estimate differences between both diets in the distribution of qualitative variables
The log-rank test was used to estimate differences in the distribution of time until insulin treatment administration or the delivery date
An estimation of the median time to insulin use, together with its 95% CI, was computed separately for each group if the test showed a statistically significant difference
To estimate differences in quantitative variables between the two groups, such as pre-delivery insulin dose, maternal weight gain in reference to the first visit and newborn glycemia, the Mann-Whitney test was used. The Mann-Whitney test was also used to estimate differences between both groups in CHO intake derived from the three-day food records (total CHO, as well as starches and sugars individually).
An intention-to-treat analysis was performed with a 95% CI and a significance level of 0.05.

Data Collection Summary:

Timing of Measurements

Subjects were seen one week after study allocation and then followed every one to three weeks, depending on clinical judgement
The first dietary assessment was made after the initial study diet prescription and a second assessment occurred after the following appointment, at which the dietary plan for the patient was revised for adherence.

Dependent Variables

Variable One: Rate of insulin treatment
Variable Two: Pregnancy outcomes (gestational age at delivery, maternal weight gain, ketonuria, maternal hypertension, Cesarean sections, SGA, LGA, macrosomia and newborn hypoglycemia).

Independent Variables
Low CHO vs. control diet.

Description of Actual Data Sample:

Initial N: 152 women (76 in each group)
Attrition (final N): 130 completed the trial, with 135 completing the first three-day food record and 97 completing the second three-day food record
Age: Control, 32.1±4.4 years; Low CHO, 33.5±3.7 years
Ethnicity: Catalonian

Other Relevant Demographics
Anthropometrics

Pre-gestational BMI: Control, 26.6±5.5kg/m²; Low CHO, 25.4±5.7kg/m²; P=0.067
Location: Catalonia, Spain.

Summary of Results:

Key Findings

		Control Group Median (p25, p75)	Low-CHO Group Median (p25, p75)	P-Value
Total CHO (g) Food Record 1	Recorded intake	202.7 (167.3, 233.1)	177.1 (153.0, 191.3)	0.0001
Total CHO (g) Food Record 1	Difference from assigned diet	-51.9 (-88.8, 23.3)	-11.7 (-35.9, 2.2)	<0.0001
Food record 2	Recorded intake	236.7 (194.7, 253.6)	187.5 (169.6, 203.4)	<0.0001
	Difference from the assigned diet	-19.3 (-61.2, 3.3)	0.07 (-18.0, 14.1)	0.0033
	Difference between food records 1 and 2	-17.2 (-48.2, 4.5)	-13.5 (-30.4, 5.2)	0.36

The intake of sugar was not different between the groups. The total CHO, sugar and starch intake increased between the first and second record and approached the prescribed diet after patients received a second dietary advice.

Other Findings

Cumulative rate of insulin treatment was 54.7% in the control group (41 of 75) and 54.7% in the Low CHO Group (41 of 75); P=1. This remained NS after adjusting for GA. There was no significant difference between the two groups with respect to insulin dose or time to insulin treatment at the first visit or at the time of the last menstrual period.
Maternal weight gain (study allocation until delivery) was higher in the control group [median, 2.1kg; interquartile range (IQR), 0.6 to 3.5] than in the Low-CHO group (median, 1.1kg; IQR, 0.3 to 2.5; P=0.017), but this difference disappeared after correction for time to follow-up [0.27kg per week (IQR, 0.11 to 0.52) vs. 0.23kg per week (IQR, 0.05 to 0.35); P=0.054]
No differences were found in other maternal and neonatal outcomes.

Author Conclusion:

We can conclude that a diet with a CHO content of 40% does not reduce the need for insulin treatment in women with GDM, compared with a high-CHO diet (55% CHO) in our population
A low-CHO diet produces similar pregnancy outcomes.

Funding Source:

University/Hospital:

University of Lleida, Lleida Spain

Reviewer Comments:

Needed 76 per group based on the power analysis but only had 67 and 68 complete the first three-day diet record and 47 and 50 complete the second three-day diet record
Unclear how compliance was assessed if diet records were missing.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	???
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		???
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	No
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	???
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	???
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes