EAL

GDM: Pharmacologic Therapy (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The objective of this trial was to investigate the failure rate of glyburide therapy in maintaining target maternal blood glucose levels and to establish specific criteria that can predict the success of glyburide therapy.

Inclusion Criteria:

From November 2000 to January 2002, all women in the UCSD Diabetes in Pregnancy clinic with GDM between 13 and 38 weeks gestation who failed to maintain target levels of maternal blood glucose levels after 1 week of dietary therapy.

Exclusion Criteria:

Excluded if not included above.

Description of Study Protocol:

Recruitment

Women attending the UCSD Diabetes in Pregnancy clinic were screened with a 1 hour, 50 g oral glucose challenge. If the women had no risk factors for GDM, they were screened at the standard gestational age of 24-28 weeks.

Criteria for screening patients earlier than 24 weeks included: obesity, history of diabetes in the immediate family and a previous pregnancy complicated by GDM.

Women with plasma glucose concentrations between 140-200 mg/dl on the 1 hour 50 g oral glucose challenge underwent a 100 g oral glucose-tolerance test. GDM was diagnosed if the plasma glucose concentration from the 1 hour, 50 g oral glucose challenge was greater than 200 mg/dl or if 2 or more of the 100 g oral glucose tolerance test values were abnormal using Carpenter and Coustan's criteria.

Upon diagnosis of GDM, patients were enrolled in a class and taught dietary therapy and capillary blood glucose monitoring. At least 1 week of capillary glucose monitoring was obtained on dietary management. Women who failed to maintain the desired glycemic control on dietary therapy (at least 20% of weekly FBS >90 mg/dl and 1-hour postprandial values >130 mg/dl) between 13 -38 weeks of gestation were enrolled in the study.

Design

Study subjects were given the choice of glyburide or insulin therapy for glucose control. Glyburide dosage was started at 2.5 - 5.0 mg/day, increased by 2.5 - 5.0 mg increments to a maximum dose of 20 mg day (10 mg BID dosing schedule). Those who failed glyburide therapy (>20 % of capillary blood glucose values > desired range on the max dose of glyburide x 1 week) were switched to insulin.

Insulin was given subcutaneously TID by the following scale:

1-18 weeks gestation: 0.7 u/kg

18-26 weeks gestation: 0.8 u/kg

26 - 36 weeks gestation: 0.9 ug/kg

36- 40 weeks gestation: 1.0 u/kg

Blinding used (if applicable): not applicable

Intervention (if applicable)

Demographic data, pertinent medical and obstetric history, glucose tolerance test restult, the four-time daily glucose values, delivery and neonatal outcomes were recorded.

Statistical Analysis

Post hoc power analysis was performed to determine the ability of the samples to detect signficant differences. Chi-square tests were used to analyze categorical data and Student's t--tests for continuous data and the Fisher's exact p-values. A receiver-operator curve was utilized to find the cut-points with the greatest sensitivity and specificity for the criteria used in predicting glyburide success.

Data Collection Summary:

Timing of Measurements

Capillary blood glucose values were measured 4 times daily.

Dependent Variables

Glycemic control - glyburide success or failure
Delivery and neonatal outcomes

Independent Variables

Choice of glyburide or insulin

Control Variables

Demographics of the women with gestational diabetes

Description of Actual Data Sample:

Initial N: 69 women

Attrition (final N): 64 women had blood glucose values available for analysis

Age: Glyburide failure 31 + 7 years, Glyburide success 32 + 5 years

Ethnicity: 87 % Hispanic

Other relevant demographics: None

Anthropometrics: No differences in either group in terms of delivery and neonatal outcomes

Location: University of California, San Diego

Summary of Results:

Characteristics	Glyburide Failure Group Mean + SD	Glyburide success group Mean + SD	Statistical Significance of Group Difference p-value
Age (year)	31 + 7	32 +5	0.017
Ethnicity no (%) White Hispanic	9 (69) 4 (31)	51 (91) 5 (9)	NS
Weight (lbs)	203 + 56	181 + 34	NS
Family history of diabetes - no (%)	5/11 (45)	23/50 (46)	NS
Previous gestational diabetes - no (%)	4/12 (33)	9/55 (16)	NS
Previous delivery of infant with macrosomia - no (%)	7 (54)	12/55 (22)	0.021
Week of gestation at gestational diabetes diagnosis	20 +8.6	27.3 + 7.5	0.003
Week of gestation at dietary therapy failure	23 + 6.9	29.7 + 6.6	0.002

Other Findings

Blood glucose concentrations measured at home before treatment in 64 women with gestational diabetes

Blood Glucose (mg/dl)	Glyburide failure N = 12	Glyburide Success N= 52	p Value
Fasting - *	126 + 19	103 + 13	<0.001
1 hour postprandials *	157+ 26	131+ 16	<0.001
Fasting **	114 +15	88+ 11	<0.001
1 hour postprandials**	145+ 20	124 +12	<0.001

* Before treatment

** During treatment

There were no signficant differences in delivery and neonatal outcomes in glyburide failure and success groups.

Author Conclusion:

Our study indicates that women clearly preferred glyburide therapy over insulin. However, over 1/6 of the women failed to achieve glycemic control and required insulin therapy. Criteria providing the highest sensitivity for glyburide success with minimal impact on specificity were:

1. Women who fail dietary therapy after 30 weeks

2. Women who fail dietary therapy before 30 weeks but have mean fasting blood glucose levels < 140 mg/dl.

Funding Source:

Reviewer Comments:

Compliance in taking glyburide and/or to dietary recommendations were not assessed so the "glyburide failure" group could have been non-adherent to medication and/or diet rather than a failure of the medication to control blood glucose levels. Authors note that lack of statistical differences between groups may be due to lack of sufficient power.

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?		???
	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?	???
	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?	???
3.	Were study groups comparable?		???
	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.)	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?	???
	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%.)	???
	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?	N/A
	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.)	N/A
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	Yes
	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?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	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?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	???
	6.6.	Were extra or unplanned treatments described?	???
	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)?	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?	No
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