Maternal Obesity Affects the Glucose-Insulin Axis During the First Trimester of Human Pregnancy

Background and objective: The maternal glucose-insulin axis is central for metabolic adaptations required for a healthy pregnancy. Metabolic changes in obese mothers in early pregnancy have been scantly described. Here we characterized the glucose-insulin axis in the first trimester of human pregnancy and assessed the effect of maternal obesity and fat mass. Methods: In this cross-sectional study, maternal blood samples (N = 323) were collected during voluntary pregnancy termination (gestational age 4⁺⁰-11⁺⁶ weeks) after overnight fasting. Smokers (N = 198) were identified by self-report and serum cotinine levels (ELISA). Maternal BMI (kg/m²) and serum leptin (ELISA) were used as proxy measures of obesity and maternal fat mass, respectively. BMI was categorized into under-/normal weight (BMI < 25.0 kg/m²), overweight (BMI 25.0-29.9 kg/m²) and obese (BMI ≥ 30.0 kg/m²), and leptin in tertiles (1st tertile: leptin < 6.80 ng/ml, 2nd tertile: leptin 6.80-12.89 ng/ml, 3rd tertile: leptin > 12.89 ng/ml). IS_HOMA insulin sensitivity index was calculated from glucose and C-peptide (ELISA) serum concentrations. Analyses of covariance including multiple confounders were performed to test for differences in glucose, C-peptide and IS_HOMA between gestational age periods, BMI and leptin groups. C-peptide and IS_HOMA were log-transformed before analyses. Results: At weeks 7-9, fasting glucose and C-peptide levels were lower (P < 0.01 and P < 0.001, respectively) and insulin sensitivity higher (P < 0.001) than at weeks 4-6. Glucose levels were not significantly different between BMI or leptin categories. In contrast, C-peptide increased by 19% (P < 0.01) between the normal weight and the overweight group and by 39% (P < 0.001) between the overweight and obese group. In the leptin groups, C-peptide increased by 25% (P < 0.001) between the 1st and 2nd leptin tertile and by 15% (P < 0.05) between the 2nd and 3rd leptin tertile. IS_HOMA decreased with higher BMI and fat mass. IS_HOMA decreased by 18% (P < 0.01) between the normal weight and the overweight group and by 30% (P < 0.01) between the overweight and the obese group. In the leptin groups, IS_HOMA decreased by 22% (P < 0.001) between the 1st and 2nd leptin tertile and by 14% (P < 0.05) between the 2nd and 3rd leptin tertile. Conclusions: At the group level, fasting glucose, C-peptide and insulin sensitivity dynamically change in the first trimester of human pregnancy. Maternal obesity is associated with higher C-peptide and lower insulin sensitivity at all periods in the first trimester of human pregnancy, while glucose is unaltered. These findings have implications for the timing of early gestational diabetes mellitus risk screening.