EAL

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 estimate the prevalence of undiagnosed, asymptomatic hypoglycemic events that occur in diabetic patients.

Inclusion Criteria:

Women with the diagnosis of gestational diabetes in the period of 2001-2003
Singleton pregnancies after completion of 24 weeks of gestation without known fetal malformations.

Exclusion Criteria:

See above

Description of Study Protocol:

Recruitment Women were recruited from diabetic clinics at Rabin Medical Center and St. Luke's-Roosevelt Hospital

Design Women were stratified by mode of treatment - insulin treated, diet only or glyburide. Data was included from nondiabetic pregnant women for comparision. Women with fasting plasma glucose levels> 95 mg/dL or 2 hour postprandial glucose >120 mg/dL on diet only were assigned to either insulin or glyburide based on the physician's preference. Starting dose of insulin was 0.7 units/kg body weight given three times daily and increased weekly as necessary. The insulin was a combination of NPH and rapid-acting. Glyburide doses were 2.5 mg/day in the morning increased by 2.5 mg the following week if necessary and thereafter by 5 mg/week up to a maximum dose of 20 mg to achieve glycemic control.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Diet therapy alone or in conjunction with insulin or glyburide if patients had fasting plasma glucose levels >95 mg/DL or who did not achieve glycemic goals on diet therapy.

Statistical Analysis

Comparisions between the groups and subgroups were performed by the analysis of variance with the Tukey multiple comparisons test or the Student t test for continuous data and the Chi Squared or Fisher exact tests for categorical data. The Pearson correlation coefficient (r) and the significance for it (P) were calculated between the variables.

Data Collection Summary:

Timing of Measurements

Continuous glucose monitoring which measured interstitial glucose levels in subcutaneous tissue within a range of 40 - 400 mg/dL every 5 minutes for a total of 288 measurements/day was done for 72 consecutive hours after at least 2 weeks of treatment was initiated. Patietnts also performed fingerstick capillary glucose measurements in the morning (fasting), 2 hours after meals and whenever a hypoglycemic incident was suspected by the patient (6-8 times/day).

Dependent Variables

Symptomatic hypoglycemic episode (blood glucose < 50 mg/dL combined with symptoms such as confusion, poor coordination, double vision, headache or combativeness).
Significant hypoglycemic episode (blood glucose < 50 mg/dL in conjunction with an inability of patients to treat their own symptoms)
Asymptomatic hypoglycemic episode (30 or > consecutive minutes of glucose determination less than 50 mg/dL detected only by the continuous glucose monitoring without patient awareness)

Independent Variables

Diet, diet plus insulin, diet plus glyburide, nondiabetic patients

Control Variables

Description of Actual Data Sample:

Initial N: 82 (27 diet only, 30 diet plus insulin, 25 diet plus glyburide), 35 controls

Attrition (final N): same as initial n

Age:

	Diet only	Insulin	Glyburide	P value
Maternal age (y)	26.4 + 3.2	28.1+ 3.9	28.l3 + 3.3	0.03* +
Prepregnancy BMI (kg/m2)	26.0 + 2.2	27.6 + 3.1	27.5 + 2.1	0.04*+
Obesity rate no (%)	10/.27 (37)	15/30 (50)	12/25 (48)	0.01*+

*Analysis of variance

+ Group 1 < Group 2 = group 3

Ethnicity: not stated

Other relevant demographics: not stated

Anthropometrics see table above

Location: New York, New York and Tel Aviv, Israel

Summary of Results:

Other Findings

No episodes of significant or symptomatic hypoglycemia events were identified in any patients.

Asymptomatic hypoglycemia: 26 of 82 (31%) of GDM compared to 0 of 35 controls (p<0.001).

Asymptomatic hypoglycemia: 19 of 30 (63%) of insulin group compared to 7 of 25 (28%) glyburide (p = 0.009, odds ratio 4.4, 95% confidence interval 1.4 - 13.9).

84 % of insulin group had nocturnal asymptomatic hypoglycemic events compared to 50 % of glyburide group.

No significant differences in rate of asymptomatic hypoglycemic episodes between obese and nonobese patients regardless of group.

Author Conclusion:

Our data suggest that asymptomatic hypoglycemic events are common during pharmacological treatment in gestational diabetic pregnancies. We speculate that this finding may be explained by treatment modality rather than the disease itself.

Funding Source:

University/Hospital:

Columbia University, Rabin Center

Reviewer Comments:

Unclear rationale for using insulin vs glyburide in selected patients - paper states "physician preference". Makes an important point about asymptomatic hypoglycemia in gestational diabetes. Wonder if ethnicity of groups from NY and Israel are similar or different.

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?	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?	???
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?	???
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	No
	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?	N/A
	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?	???
	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?	???
	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?	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