GDM: Postpartum Care (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  • to determine the long-term incidence of diabetes among Danish women with previous diet-treated GDM
  • to describe changes in the incidence of diabetes and overweight during the last decades among women with previous GDM
  • to identify risk factors for the development of diabetes
Inclusion Criteria:

"Old" cohort

  • Diagnosis of diet-treated GDM during 1978-1985  by 3-h, 50-g OGTT
  • Attended center for diabetes and pregnancy, Rigshospitalet (Denmark)

"New" cohort

  • Diagnosis of diet-treated GDM during 1987-1996  by 3-h, 75-g OGTT
  • Attended center for diabetes and pregnancy, Rigshospitalet (Denmark)
Exclusion Criteria:
  • Women attending clinic in 1986 - during 1986 the 50-g OGTT was replaced by a 75-g test
  • Women diagnosed with GDM and treated with insulin
  • Women with overt diabetes within 6 months of pregnancy (n=12)
Description of Study Protocol:

Recruitment

  • Attendees of clinic diagnosed with diet-treated GDM from 1978-1996 (excluding those attending in 1986) were invited by mail to participate in the study. GDM screening was based on risk factors (family history of diabetes, prepregnancy overweight [>20% overweight]  or BMI >=27 kg/m2 [from 1994], previous macrosomic infant [birth weight >=4,500 g], glucosuria, previous GDM, and age >=35 years [from 1994]) and fasting blood glucose (capillary whole blood >=4.1 or capillary plasma >=4.7 mmol/l) 

Design

  • Women with diet-treated GDM during 1978–1985 (old cohort, n = 241, also followed up around 1990) or 1987–1996 (new cohort, n = 512) were examined in 2000–2002. 
  • Outcome of diabetes was assessed by a 2-h, 75-g oral glucose tolerance test according to the World Health Organization criteria or an intravenous glucagon test supplemented by measurement of GAD antibodies.
  • Historical data from index-pregnancy and anthropometrical measurements were collected

Blinding used (if applicable): not mentioned

Intervention (if applicable): not applicable

Statistical Analysis

  • Median and interquartile range or number (percent)
  • {chi}2 test for categorical, Mann-Whitney U test for continuous variables
  • Uni- and multivariate logistic regression, using manual backward elimination and forward selection : In one model, the dependent variable was diabetes at follow-up for the old cohort in 1990 and for the new cohort in 2002, 3.5–15 years after index pregnancy. In three other models, the dependent variable was diabetes at follow-up in 2002 (type 1 or type 2 diabetes, type 2 diabetes, or type 1 diabetes), 3.5–23.2 years after index pregnancy.
  •  A two-sided P value <0.05 was considered significant
  • SPSS for Windows, version 11.0, was used for statistical analysis.
Data Collection Summary:

Timing of Measurements

  • Women were offered an OGTT 2 months postpartum and in 1- to 2-year intervals, unless diabetes was diagnosed.

Dependent Variables

  • Diabetes Diagnosis  - OGTTs were defined as abnormal if two or more of seven values during the test exceeded 3 SDs above the mean for a group of normal-weight nonpregnant women without family history of diabetes examined in exactly the same manner (e.g., fasting venous plasma glucose 6.4 and 6.2 and 2-h plasma glucose 7.6 and 8.9 mmol/l, respectively)
  • Glucagon test- Women reporting insulin-treated diabetes (n = 22) were examined by a 6-min glucagon test, where 1 mg glucagon (Glucagen; Novo Nordisk) was injected intravenously to evaluate pancreatic ß-cell function (16). If fasting serum C-peptide was <300 pmol/l and 6-min C-peptide was <600 pmol/l, then the woman was classified as having type 1 diabetes

Independent Variables

Abstraction of medical records for:

  • new/old cohort
  • Nordic origin
  • prepregnancy BMI
  • smoking
  • parity
  • family history of diabetes
  • GDM diagnosis before 24 gestational weeks
  • quartiles of fasting glucose from the diagnostic OGTT in pregnancy
  • preterm delivery (gestational age <37 weeks)
  • age at delivery
  • impaired glucose tolerance (IGT) postpartum (old cohort: two or more values above mean + 3 SD; new cohort: 2-h glucose >= 7.8 mmol/l)
  • age at follow-up.

Control Variables

  • length of follow-up
Description of Actual Data Sample:

Initial N: 241 from the old cohort and 512 from the new cohort

Participation Rate (final N): 64% (n = 481)

  • 151/241 of old cohort
  • 330/512 of new cohort of the total population was included.
  • Reasons for not participating were refusal (n = 167), no response (n = 71), death (n = 8), severe illness other than diabetes (n = 7), pregnancy (n = 6), and emigration (n = 13).

    Age: Median age of participants (31.7) did not significantly differ from non-participants (30.6)

    Ethnicity: 75% of participants were of Nordic origin compared to 76.9% of non-participants (p=0.552)

    Other relevant demographics:

    Anthropometrics

    • Non-participants had a higher pre-pregnancy BMI (26.9 vs. 25.1)
    • Non-participants had a higher percentage with diabetes at latest routine follow-up (36.8 vs. 24.4)

    Location: Center for Diabetes and Pregnancy, Rigshospitalet (Denmark)

  • Summary of Results:

     Table 3— Crude and adjusted ORs for independent variables tested in multiple logistic regression with the dependent variable overt diabetes at follow-up in 1990 for the old cohort and in 2002 for the new cohort

      Crude OR (95% CI) Adjusted OR (95% CI)*

    n (diabetes/total{dagger}) 164/556 142/506
    New cohort 2002 vs. old cohort 1990 3.1 (2.1–4.7){ddagger} 3.1 (1.9–5.3){ddagger}
    Prepregnancy BMI <25 kg/m2 1.0 1.0
    Prepregnancy BMI >=25 and <30 kg/m2 2.4 (1.5–3.8){ddagger} 2.0 (1.1–3.4)§
    Prepregnancy BMI >=30 kg/m2 3.2 (2.0–5.0){ddagger} 2.6 (1.5–4.5)§
    GDM diagnosis before gestational age of 24 weeks 3.7 (2.1–6.3){ddagger} 2.3 (1.2–4.5)||
    Fasting plasma glucose at diagnosis of GDM (mmol/l) 2.1 (1.3–3.2)§ 2.5 (1.5–4.2){ddagger}
    IGT 2 months postpartum{dagger} 3.9 (2.5–6.0){ddagger} 5.8 (3.3–9.9){ddagger}
    Preterm delivery (gestational age <37 weeks) 2.2 (1.3–3.8)§
    Age at follow-up 1.1 (1.0–1.1){ddagger}
    Family history of diabetes 1.5 (1.0–2.1)||
    Other ethnic origin than Nordic 1.7 (1.1–2.6)||

    Only statistically significant ORs are presented.

    * Adjusted for the other independent variables in the final model and follow-up length as a noncontinuous variable.

    {dagger} The total number includes women from the old cohort at the 1990 follow-up and from the new cohort at the 2002 follow-up. Women with overt diabetes postpartum were not included in the analyses (n = 12). As a result of the OGTT, postpartum is included in the final model, and as only 87.5% had an OGTT postpartum, the total number of women included in the final model was lower than the total number of all the participants. The final model only includes women with available data on all the variables.

    Table 4— Adjusted ORs for the independent variables tested in multiple logistic regression with diabetes, known type 2 diabetes, or known type 1 diabetes as the dependent variable at follow-up in 2002

      Diabetes Type 2 diabetes Type 1 diabetes

      Adjusted OR (95% CI)* Adjusted OR (95% CI)* Adjusted OR (95% CI)*
    n in full model (diabetes/total){dagger} 162/425 143/417 16/430
    Prepregnancy BMI <25 kg/m2 1.00 1.00
    Prepregnancy BMI >=25 and <30 kg/m2 2.2 (1.3–3.8){ddagger} 2.6 (1.5–4.7){ddagger}
    Prepregnancy BMI >=30 kg/m2 3.0 (1.7–5.2)§ 4.2 (2.3–7.4)§
    Family history of diabetes 1.9 (1.2–3.2){ddagger}
    Diagnosis before gestational age 24 weeks 3.6 (1.7–7.3){ddagger} 2.9 (1.5–5.9){ddagger}
    Fasting plasma glucose at diagnosis of GDM (mmol/l) 2.3 (1.3–3.8){ddagger} 2.1 (1.2–3.6){ddagger}
    IGT postpartum 4.4 (2.5–7.7)§ 3.5 (2.06.0)§ 2.8 (1.0–7.9)||
    Preterm delivery 3.2 (1.1–9.9)||

    Only statistically significant ORs are presented.

    * Adjusted for the other independent variables in the final model, including cohort effect (old versus new cohort) and follow-up length as a continuous variable.

    {dagger} Women with overt diabetes postpartum were not included in the analyses (n = 12). The total number is the number of women from both cohorts in 2002 included in the final model and with available data on all the variables. As a result of the OGTT, postpartum is included in the final models, and as only 87.5% had an OGTT postpartum, the total number of women included in the final models was lower than the total number of all the participants.

    {ddagger} P < 0.01 ;§ P < 0.0005 ;|| P < 0.05

    Highest quartile of fasting glucose compared with the three lowest quartiles: 75th percentile = 5.6 mmol/l.

    Other Findings

    • 481 women were followed for 9.8 years (interquartile range 6.4–17.2)
    • Diabetes was present in 192 (39.9% [95% CI 35.5–44.3]) and IGT/impaired fasting glucose (IFG) in 130 (27.0% [23.1–31.0]) women.
    • 21 had type 1 and 171 type 2 diabetes. 
    • Median BMI was 27.9 kg/m2 (24.1–32.9). BMI >25 kg/m2 was found in 60.9%, and 31.6% were obese.  
    Author Conclusion:

    There was a doubling in the incidence of diabetes and IGT/IFG over a 10-year period.The study supports previous findings that women with GDM are at high risk for subsequent diabetes. The risk is further increased if obesity is present before pregnancy.  Women with previous GDM represent a target group for intervention to postpone or prevent the development of overt diabetes.

    Funding Source:
    Government: Danish Medical Research Council
    University/Hospital: Copenhagen University
    Not-for-profit
    0
    Foundation associated with industry:
    Reviewer Comments:
    • There were differences between participants and non-participants on important characteristics (higher BMI, % with diabetes), so it is unclear whether the sample is representative of the true incidence of diabetes
    • Survival analysis methods may have been more appropriate than logistic regression due to losses to follow-up
    • No mention of blinding for collection of historical data
    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) N/A
      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) N/A
     
    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? N/A
      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? ???
    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? No
      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? 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.) 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? ???
      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? 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.) Yes
      5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? ???
      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? Yes
      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? 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? N/A
      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? ???
      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? ???
      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)? 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