Background and aim: Gestational diabetes mellitus (GDM) is a glucose intolerance first diagnosed during pregnancy. It affects 10.9 % of pregnant women in Switzerland, with long-term consequences for the mothers and their offspring. GDM increases the risk to type 2 diabetes after 5-10 years by around 60%. The pathogenesis of GDM generally includes increased prepartum insulin resistance and beta-cell dysfunction. In the long-term, it remains controversial, if the increased insulin resistance, lower insulin secretion or a combination of both increases the maternal risk for diabetes. The aims of the study were to describe changes in insulin sensitivity and secretion during and after pregnancy and their role to predict prediabetes at 1 year postpartum in women with GDM.
Methods: We used a study population from an ongoing randomized controlled study (MySweetheart). Between 2016 and 2020, 194 women with GDM were recruited in the 3rd trimester of pregnancy and followed up to 1 year postpartum. They were 1:1 randomized into an intervention group and in a control group (treatment-as-usual). Between 24 and 32 weeks of pregnancy, we took fasting samples at the baseline visit, and at 6-8 weeks and at 1 year postpartum, measures of glucose and insulin were taken at 0, 30, 60, 90 and 120 minutes after performing a 75g oral glucose tolerance test Using glucose and insulin measurements, we calculated insulin sensitivity and resistance indices (Matsuda index and homeostatic model assessment insulin resistance (HOMA-IR)) and "unadjusted or raw" insulin secretion (area under the curve (AUC) and insulinogenic index (IGI)). Finally, we calculated the Adjusted Secretion Index for Insulin Sensitivity (ISSI-2). It adjusts insulin secretion for ambient insulin sensitivity, so it is used to evaluate the compensation of the beta-cells for insulin resistance.
Results: Of the 97 participants of the control group, 90 participated at the early (6-8 weeks) and 50 at the late (1 year) postpartum. Between the early and late postpartum, women lost 1.97 ± 5.09 kg (p=0.003). However, insulin resistance (HOMA-IR) increased by 49 % and (peripheral) insulin sensitivity (Matsuda index) decreased by 25.3% in this same period (p<0.001). Raw insulin secretion calculations (AUC and IGI) increased by 8 % and 19.5 % (all p≤0.063), respectively, while the adjusted disposition index (ISSI-2) decreased by 19.9 % (p=0.0053). Clinically, fasting glucose increased by 0.42 ± 0.56 mmol/l (p<0.001), while prevalence of glucose intolerance almost doubled during this same period (from 21.3 % to 36.6 %). At the baseline visit, HOMA-IR predicted prediabetes at 1 year postpartum (p=0.012). At 6-8 weeks postpartum, all insulin resistance and sensitivity values as well as the disposition index predicted later prediabetes (all p≤0.07). However, raw insulin secretion measures did not.
Conclusion: Despite weight loss, insulin sensitivity as well as adjusted beta-cell function, decreased between early and late postpartum and glucose intolerance increased. During their pregnancy, insulin resistance (HOMA-IR) could already be used for early risk stratification in women with GDM. This study highlights the importance of the postpartum period in this population at high risk of developing diabetes mellitus later.