GDM: Pharmacologic Therapy (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
The purpose of this study was to evaluate pregnancy outcome in a population of women with Gestational Diabetes Mellitus (GDM) given differing glucose targets in fuction of the ultrasound measurement of insulin-sensitive tissues.
Inclusion Criteria:
  • Women with GDM diagnosed between 24 and 28 weeks gestation
  • Singleton pregnancies
  • Without medical complications other than GDM
Exclusion Criteria:
  • Multiple fetuses
  • Women with medical complications in addition to GDM
Description of Study Protocol:

Recruitment

Women were recruited from 3 hospitals in Italy

Design

Upon enrollment into the study, patients were randomized into 1 of 2 protocols: C (conventional) or M (modified). Each protocol group was stratified by pre-pregnancy BMI (<20, 20-26, >26).

Blinding used (if applicable)

None used.

Intervention (if applicable)

Regular insulin before meals or Isophane insulin at bedtime was added (starting at 0.1 U/kg/injection) or the dose was modified (2-3 u/injection) when BG was highter than predetermined target - fasting, post-breakfast, post-lunch or post-dinner. Dietary prescriptions were adjusted to maintain BG below target.

C group's glycemic target was 90 fasting/120 post-prandial mg/dl regardless of fetal biometry.

M group's glycemic targets differed according to fetal abdominal circumference centile (AC): 80/100 mg/dl  if > 75th, 100/140 if < 75th.

Statistical Analysis

Student's t test was used to assess differences in means among groups. Categorical data were evaluated by Pearson chi-squared test with Yates correction. Statistical signficance was set at p <0.05.

 

Data Collection Summary:

Timing of Measurements

  • Both groups were taught to monitor capillary glucose levels using memory reflectance meters at least 4 times/day.
  • Ultrasound exams for fetal biometry were scheduled every 2 weeks for Group M and at 34 and 38 weeks for group C.
  • Metabolic controls were scheduled every two weeks for both groups.
  • Hypoglycemic monitoring of the neonates was done immediately after birth, then every 30 minutes x the first 3 hours, then hourly x the next 6 hours.

Dependent Variables

  • For abdominal circumference > 75th %ile, requiring insulin
  • For AC <75th %ile, requiring insulin
  • Neonates with macrosomia
  • Neonates classified as LGA

Independent Variables

  • Conventional therapy (C)
  • Modified therapy (M)

Control Variables

 

Description of Actual Data Sample:

Initial N: 240 women (80 in group C and 160 in group M)

Attrition (final N): 229 women (78 in group C and 151 in group M)

Age: Group C: 33.5 + 4.2 years, Group M:  33.8 + 4.6 years

Ethnicity: not mentioned

Other relevant demographics:

Anthropometrics:

No signficant differences between groups C and M in age, BMI, parity, abdominal circumference, plasma glucose, HbA1c or fructosamine levels at entry

Location:

Women were followed in one of 3 hospitals in Italy

 

Summary of Results:

 

Variables

Group C

%

Group M

%

Statistical Significance of Group Difference

AC > 75th% ile,insulin treatment required 15.4 59.7 p < 0.01

AC < 75th %ile, insulin treatment required

 17.9

 10.1

 p< 0.01

Neonates classified as LGA

 17.9

 7.9

 p< 0.05

Neonates classifed as macrosomic

11.5

3.3 p< 0.05
Neonates classifed as SGA 10.3 6 NS

AC >  75th %ile with neonates LGA

30.8 7.9 p< 0.001
AC > 75th %ile with neonates classifed as macrosomic 17.8 4.5 p <0.001
AC <75th %ile, neonates SGA 30.3

14.5

 

p <0.001

Other Findings

 

Author Conclusion:

Our data show the value of a flexible ultrasound based approach to the the treatment of GDM. This model does not necessarily involve a generalized aggressive treatment, allowing to concentrate therapeutic effects on a small subgroup of women showing indirect ultrasound evidence of fetal hyperinsulinzation. Such a selective approach allowed to obtain near-normalization of fetal growth, with clear advantages on global pregnancy outcome.

Funding Source:
Reviewer Comments:
Subjects numbers in groups are not similar but there were no significant differences between groups.
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) 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? 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? ???
  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.) 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? 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? ???
  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)? ???
  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? N/A
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