EAL

GDM: Abnormal Glucose Tolerance During Pregnancy (2008)

Citation:

Study Design:

Class:

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Quality Rating:

Research Purpose:

The purpose of this study was to evaluate the consequences of very mild forms of gestational glucose intolerance, defined by an elevated 50 gram glucose challenge test followed by a normal oral glucose tolerance test.

Inclusion Criteria:

Women of Caucasian origin seen at the Diabetic and Pregnancy Centre of Niguarda Ca'Granda Hospital in Milan, Italy
Pregnant women with and elevated glucose challenge test (GCT) as defined by plasma glucose 60 mintues after challenge > 7.8 mmol/l followed by a normal oral glucose tolerance test (OGTT)

Exclusion Criteria:

Women with a normal GCT
Women with a diagnosis of GDM
Women with only 1 normal value on the OGTT

Description of Study Protocol:

Recruitment:

Subjects were recruited through a screening procedure at the Diabetic and Pregnancy Centre of Niguarda Ca’Granda Hospital in Milan, Italy from 1997-2002. Only women of Caucasian origin were considered. For those with standard risk factors for the disorder as defined in 1996 by the Italian Society of Diabetology the screening was done at booking. Women with a normal screening test were re-tested from weeks 24-28, at which time all those without risk factors were also tested. The screening procedure consisted of a 50 gram GCT with a 1 hour blood glucose cut-off set at 7.8 mmol/l. Women with a positvbe screening test underwent a confirmatory 100 gram OGTT within 7 days, evaluated using Carpenter and Coustan’s criteria. The complete diagnostic path was repeated at week 30 -34 in women with a positive GCT but without a diagnositic OGTT.

Design:

After diagnosis, women with borderline gestational glucose intolerance (BGGI) were stratified according to age ( <25, 25-35, 35 years) and body mass index (BMI) (< 19.8, 19.8 – 26, 26 kg/m2), then randomly assigned to one of two study groups:

Group A (no treatment): women were assured after testing, and were given no special care, diet, or pharmacological treatment.
Group B (treatment): women were immediately given dietary advice providing 24-30 kcal/kg per day, based on prepregnancy body weight; caloric intake was divided into three meals and two or three snacks, and distributed as 50-55% carbohydrate; 25-30% protein, 20-25% fat. They then entered an outpatient management protocol, which involved visits every 2 weeks, when the main clinical parameters (weight, blood pressure) were recorded, discussion of dietary habits with evaluation of therapeutic compliance, and measurement of fasting and 2 hour postprandial blood glucose, of HBAIC, and fructosamine. Blood glucose targets were <5 mmol/ fasting and <6.7 mmol/l 2 hour postprandial. Urine was tested every morning at home for ketone bodies.
Group C was established by selecting for every pair of women enrolled in Groups A and B the first screened woman with normal GCT at screening, falling into the same stratification category for age and BMI.

Blinding used (if applicable): None used

Intervention (if applicable):Women in the intervention group were immediately given dietary advice providing 24-30 kcal/kg per day, based on prepregnancy body weight; caloric intake was divided into three meals and two or three snacks, and distributed as 50-55% carbohydrate; 25-30% protein, 20-25% fat. They then entered an outpatient management protocol, which involved visits every 2 weeks, when the main clinical parameters (weight, blood pressure) were recorded, discussion of dietary habits with evaluation of therapeutic compliance, and measurement of fasting and 2 hour postprandial blood glucose, of HBAIC, and fructosamine. Blood glucose targets <5 mmol/ fasting and <6.7 mmol/l 2 hour postprandial. Urine was tested every morning at home for ketone bodies.

Statistical Analysis

Data are expressed as means + SD, median or percentages. Normality of distribution of all variables was checkedc and if necessary a stuitable transformation was adopted.

Paired and unpaired student’s T tests or analysis of variance and Scheffe’s test were used to assess differences in means between groups. Categorical data were evaluated by the Chi Squared test with Yates corrections. The Kruskal-Wallis test was used for the comparision of medians. Statistical significance was set at p<0.05

Data Collection Summary:

Timing of Measurements

Measurements were taken upon diagnosis and at delivery for the mother and at birth, and hourly for the neonate for 3 hours post-delivery.

Dependent Variables

Maternal characteristics (plasma glucose, hemoglobin A1c, serum fructosamine, rate of Caesarean sections)
Neonatal outcomes (rates of macrosomia, large for gestational age (LGA), small for gestational age (SGA), hypoglycemia, hyperbilirubinemia, polycythemia, 5 minute Apgar score <7, admission to neonatal intensive care unit (NICU)

Independent Variables:

Standard treatment for BGGI versus dietary treatment and regular monitoring

Control Variables:

Age and BMI were stratified

Description of Actual Data Sample:

Initial N: 321 were randomized to treatment

Attrition: Final n consisted of 300 subjects (150 Group A, 150 Group B) Group C consisted of 150 subjects also

Age: Age ranged from <25 and >35 years, there were no significant differences in age between groups

Ethnicity: Caucasian

Other relevant demographics:

Anthropometrics There were no significant differences in BMI, parity and fasting plasma glucose between groups A and B. Post-challenge blood glucose in all women with BGGI was 8.44 + 0.89 mmol/l, significantly higher (p<0.05) than in control subjects (group C). 6.44 + 0.91 mmol/l.

Location: Milan, Italy

Summary of Results:

Neonatal outcomes	BGGI Group A	BGGI Group B	Control C	P value
LGA (%)	14.0	6.0	9.1	0.046
Ponderal index (g x 100 cm²)	2.73 + 0.35	2.64 + 0.24	2.64 + 0.30	0.030
Macrosomes (%)	10.7	5.3	8.0	NS

There were no signficant differences between the 3 groups in maternal age, percent primipara, BMI or fasting plasma glucose at diagnosis.

Group B had significantly different fasting plasma glucose values at diagnosis and during treatment (4.68 + 0.45 vs. 4.38 + 0.45, p <0.001) and significantly differenct 2 hour postprandial plasma glucose valuess (6.00 + 0.57 vs. 5.43 + 0.68 , p<0.001).

Author Conclusion:

Even very mild alterations in glucose intolerance can result in excessive or disharmonious fetal growth, which may be prevented by simple, non-invasive therapeutic measures.

Funding Source:

Reviewer Comments:

Well done study.

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?	Yes
	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)	???
	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.)	Yes
	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?		Yes
	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%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	Yes
	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?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	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.)	No
	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?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	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)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	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