Lactation Protects Against T2DM in Women With Recent GDM
Research Design and Methods
Participants
The prospective German GDM study has followed women with GDM for the development of postpartum diabetes from delivery. As previously described, between 1989 and 1999, 304 patients with GDM were recruited across Germany. GDM was diagnosed according to the criteria of the German Diabetes Association. Women were considered to have GDM if two of three capillary blood glucose values exceeded 5 mmol/L (fasting) before an oral glucose tolerance test (OGTT), 10.6 mmol/L at 60 min, and 8.9 mmol/L at 120 min after the OGTT. These diagnostic criteria were consistent during recruitment. All centers participating in the study were asked to follow the therapeutic guidelines for the treatment of GDM recommended by the German Diabetes Association. According to these recommendations, insulin was required if capillary blood glucose values exceeded 5 mmol/L before a meal or 7.8 mmol/L at 60 or 120 min after a meal for at least 1 week despite dietary interventions. Of the participants, 206 women gave birth to their first child, 63 to the second child, 24 to the third, and 11 to the fourth child. All patients gave written informed consent to participate in the study. The study was approved by the ethical committee of Bavaria, Germany (Bayerische Landesärztekammer Nr. 95357).
Outcome Measure
Patients were followed for the development of diabetes postpartum by means of an OGTT at 2 and 9 months; 2, 5, 8, 11, 15, and 19 years after pregnancy; or until the diagnosis of diabetes. OGTTs were performed by the patient physician. An OGTT was conducted at 2 months as part of the recommended routine postpartum testing in women with GDM. All subsequent follow-up OGTTs were performed as part of the study protocol. In addition, if women presented with symptoms of diabetes between follow-up visits, physicians performed blood glucose measurements to test for clinical diabetes. For the study outcome, diabetes onset was defined according to American Diabetes Association criteria, which include unequivocal hyperglycemia with acute metabolic decompensation or the observation on at least two occasions of 1) a 2-h plasma glucose level >200 mg/dL after an oral glucose challenge, or 2) a random blood glucose level >200 mg/dL if accompanied by unequivocal symptoms. Since 1997, a fasting blood glucose level >126 mg/dL on two occasions also has been included as a diabetes diagnosis criteria in the study. Follow-up is ongoing, and this analysis includes follow-up data until November 2011. Of the 304 patients who were recruited, 98 women (32%) left the study during the 15-year follow-up without developing diabetes and were considered dropouts.
Questionnaires and Interviews
Age at delivery, diabetes treatment during pregnancy, smoking behavior during pregnancy, and parity status were obtained shortly after delivery. BMI was recorded by the gynecologists at the first obstetric visit and was extracted from the obstetric records at a median gestational age of 8 weeks (interquartile range [IQR] 7–10 weeks). Data on lactation (yes/no), the duration of lactation, and full lactation were obtained from questionnaires completed by the child's mother when the child was aged 9 months. If the child still was being breastfed at 9 months of age, the same questionnaire was completed again when the child was 2 years of age. Pregnancies after this index pregnancy were not considered in the analysis. Other details of the study protocol and the measurement of islet autoantibodies are described elsewhere.
Statistical Analysis
The development of diabetes after delivery was used as the outcome measure. Variables analyzed with respect to diabetes risk were diabetes treatment during pregnancy (insulin or diet), BMI (>30 kg/m or ≤30 kg/m as obese and nonobese, respectively), and duration of breastfeeding (no breastfeeding, breastfeeding ≤3 months, breastfeeding >3 months, no full breastfeeding). Time to event methods were used to calculate risks (life-table analysis) and compare outcomes (postpartum diabetes) among patients stratified according to these factors using a Cox proportional hazard model. The outcomes were compared by univariate analysis, and significant risk factors were entered into a multivariate analysis. For all analyses, two-tailed P values <0.05 were considered statistically significant. SPSS version 19 (SPSS Inc., Chicago, IL) was used for statistical analysis.