GDM: Abnormal Glucose Tolerance During Pregnancy (2008)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:
Gestational diabetes mellitus (GDM) defined by two abnormal glucose values on a 3-h oral glucose tolerance test (OGTT) is associated with insulin resistance and a low serum concentration of adiponectin. The metabolic implications of impaired glucose tolerance (IGT) of pregnancy (i.e., a singleton abnormal value on an OGTT), however, are not well established. The researchers sought to evaluate the metabolic phenotype of pregnant women with IGT in relation to the timing of their isolated hyperglycemia.
Inclusion Criteria:
  • Participants consisted of 180 healthy pregnant women attending outpatient obstetrics clinics, who had been referred for a 3-h, 100-g OGTT after an abnormal result on a screening 50-g glucose challege test (GCT) (plasma glucose > 7.8 mmol/l) at 1 h after challenge.
  • The study was approved by the Research Ethics Board at Mount Sinai Hospital, and all study participants gave written informed consent.

 

Exclusion Criteria:
Criteria was not detailed.
Description of Study Protocol:

Recruitment Method was not detailed.

Design Cross-Sectional Study

Blinding used:  not applicable 

Intervention:  not applicable

Statistical Analysis  

  • All analyses were conducted using SAS version 8.02 (SAS Institute, Cary, NC).
  • P<0.05 was considered statistically significant.
  • Means + SEs were presented by study group, with ANOVA used to assess univariate differences among continuous variables and X2 used for categorical variables.
  • The distributions of ISOGTT and adiponectin were skewed, and thus natural logarithmic transformations of these variables were used to identify subjects in univariate and multivariate analyses.
  • ANCOVA was used to test differences in glycemic parameters (1-h blood glucose blood glucose results on a 50-g GCT, fasting blood glucose. and AUC glucose), ISOGTT, and adiponectin.
  • Multiple linear regression analysis of dependent variables logarithmically transformed ISOGTT was used to determine factors that were independently associated with insulin sensitivity.
Data Collection Summary:

Timing of Measurements

Current glucose intolerance (GDM, 1-h IGT, or 2-h/3h IGT) - venous blood samples for measurement of insulin were drawn at fasting and hourly during the OGTT.

The plasma adiponectin concentration was measured at 3 h postglucose [the adiponectin level is not affected by food intake] by radioimmunoassay (Linco Research, St Charles, MO) with a coefficient of variation of 9.3%).

Dependent Variables

Diagnostic Criteria:

  • Current glucose intolerance (GDM, 1-h IGT, or 2-h/3h IGT) - venous blood samples for measurement of insulin were drawn at fasting and hourly during the OGTT.
  • Specific insulin was measured using the Roche Elecys 1010 immunoassay analyzer and the electrochemiluminescence immunoassay kit. This assay shows a 0.05% cross-reactivity to intact human proinsulin and the primary circulating split form *des -31,32).
  • The plasma adiponectin concentration was measured at 3 h postglucose[ the adiponectin level is not affected by food intake] by radioimmunoassay (Linco Research, St Charles, MO) with a coefficient of variation of 9.3%).  
  • The OGTT stratifies participants into three glucose tolerance groups: 1) GDM as defined by the National Diabetes Data Group (NDDG) criteria (requires at least two of the following: fasting glucose >5.8 mmol/l, 1-h postload glucose >10.6mmol/l,2-h glucose > 9.2 mmol/l, or 3-h glucose >8.1 mmol/l); 2) IGT, as defined by meeting only one of above criteria; and 3)NGT, defined as subjects not meeting any of the NDDG criteria.
  • In the current analysis, the above definition of IGT has been used to identify subjects with an intermediate degree of glucose intolerance (between NGT and GDM), as evidenced by their single abnormal glucose value. 
  • Of the 39 subjects with IGT, 15 met the 1-h criteria, 10 met the 2-h criteria, 13 met the 3-h criteria, and only 1 person exceeded the fasting threshold. The IGT subjects were stratified into two groups:1) 1-h IGT (comprising subjects with isolated hyperglycemia at 1h) and  2) 2-h/3-h IGT (comprising subjects with isolated hyperglycemia at either 2 or 3 postglucose). Those, in combination with GDM and NGT, there were four study groups in total. 

Independent Variables:

Demographic and historical information was obtained by an interview-administered questionnaire at the time of the OGTT.

  • Age
  • Weeks’ gestation, prepregnancy BMI
  • Weight gain during pregnancy
  • Ethnicity
  • Previous GDM
  • Family history of diabetes

Control Variables

 

 

Description of Actual Data Sample:

Initial N: GDM=48;1-h IGT (single elevated value at 1 h, n=15); 2-h/3-h IGT (single elevated value at either 2 or 3 h (n=23); and normal glucose tolerance (NGT, n=93).

Attrition (final N):  as above

Age: See Table 1

Ethnicity: See Table I

Other relevant demographics:

Anthropometrics

Location: Division of Endocrinology, University of Toronto, Ontario, Canada.

 

Summary of Results:

There was no significant differences among the variables examined for the groups. A history of GDM in a previous pregnancy, however, was much more prevalent in the GDM group (18.8%) prevalence within group) and 1-h IGT group (20% prevalence than in the 2-h/3-h IGT group (4.4%) and the NGT group (4.3%) (overall P=0.0159)(Table 1).

Table 1 Demographic and clinical data by glucose tolerance group

-

GDM

1-h IGT

2-h/3-h IGT

NGT

n

48

15

23

93

-

Age (years)

34.0 +  0.6

33.4 + 1.2

32.4 + 0.9

33.2 + 0.5

0.5061

Weeks’ gestation

29.1 +  0.4

29.9 +  0.6

29.6 +  0.5

29.2 +  0.3

0.6405

Prepregnancy BMI (kg/m2)

24.7 +  0.7

23.2 +  1.2

24.4 +  1.0

23.9 +  0.5

0.6290

Weight gain in pregnancy(kg)

11.7 +  0.7

11.2 +  1.2

11.2 +  1.0

11.0 +  0.5

0.8775

Ethnicity

-

-

-

-

0.2383

Caucasian (%)

62.5

60.0

78.3

62.4

-

Asian (%)

10.4

13.3

13.0

19.4

-

South Asian (%)

27.1

26.7

4.4

14.0

-

Other (%)

0

0

4.4

4.3

-

Family history of diabetes (%)

62.5

60.0

56.5

45.2

0.2195

Previous GDM (%)

18.8

20.0

4.4

4.3

0.0159

* Data are means + SE or %.  ¶ P values represent overall differences across groups as determined by ANOVA for continuous variables and x2 for categorical variables.

Other Findings:

  • The evaluation of glycemic parameters (1-h blood result on a  50-g GCT, fasting blood glucose, and AUCglucose from the OGTT) also suggested a pattern wherein 1-h IGT bore similarity to GDM and 2-h/3-h IGT resembled NGT.
  •  The 1-h GCT result was highest in the GDM group (9.2 mmol), followed in turn by 1-h IGT (8.8 mmol/l) and, 2-h/3-h IGT (8.6 mmol/l), and NGT (8.4 mmol/l) groups, respectively (trend P<0.0001). 
  • Both fasting blood glucose and AUCglucose exhibited the same pattern (GDM >1-h IGT >2-h/3-h IGT>NGT) (both trend P< 0.0001). 
  •  IS ogtt was highest in the NGT group (5.1), followed in turn by the 2-h /3-h IGT (4.6), 1-h IGT (3.8) and GDM (3.2) groups, respectively (trend P<0.0001).
  • Adiponectin levels were higher in the NGT (15.7 µ g/ml) groups followed in turn by the 1-h IGT (13.7 µg/ml) and GDM (11.8 µg/ml) and GDM (11.8 µg/ml) groups, respectively (trend P=0.0058). 
  • The relationship noted were essentially unchanged by adjustment for potential covariates including age, weeks’ gestation, prepregnancy BMI, weight gain in pregnancy, ethnicity, previous GDM, and family history of GDM.

 

Author Conclusion:

Conclusion

  • The metabolic implications of IGT in pregnancy vary in relationship to the timing of the abnormal glucose value from the diagnostic OGTT.
  • IGT at 1 h was associated with greater hyperglycemia, higher insulin resistance, and lower adiponectin concentration than IGT at 2 or 3 h post challenge.
  • Furthermore, the metabolic phenotype associated with 1-h IGT resembles that of GDM, whereas that for IGT at 2 or 3 h exhibits similarity to that for NGT.
  • From a clinical perspective, these findings raise the intriguing possibility that IGT at 1 h may identify women at risk of adverse pregnancy outcome and postpartum diabetes.  A longitudinal study is needed to address this possibility.

 Limitations:

  • The cross-sectional nature of this study precluded inference on causal relationship. In particular, the researchers were unable to address the relationship between the timing of IGT on an OGT and either pregnancy outcome or postpartum diabetes.
  • Due to the absence of data on maternal diet in the days preceding the OGTT, the researchers noted that is was conceivable that differences in carbohydrate intake on those days could have affected findings in women with IGT.
  • It should also be noted that almost all study participants, including those comprising the NGT group, had a positive GCT result before recruitment. Thus, findings with this NGT group may not reflect a truly normal patient population (i.e., with normal screening GCT and normal results on a diagnostic OGTT).
Funding Source:
Reviewer Comments:

A cross sectional study measures the prevalence of health outcomes or determinants of health, or both, in a population at a point in time or over a short period. However, associations must be interpreted with caution. Bias may arise because of selection into or out of the study population. A cross sectional design may also make it difficult to establish what is cause and what is effect.  

The limitations and critique of the study, as stated by the authors appear to be very appropriate.

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? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
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) N/A
  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? Yes
  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.) Yes
  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? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  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? 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? N/A
  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? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  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? N/A
  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? ???
  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? No
  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)? ???
  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