Arum¹, A. Kdekian¹, M.K. Veenstra², M. Sietzema², H.L. Lutgers^2,3, J.K. Kruit¹, E.M. van der Beek¹

¹Department of Pediatrics, UMCG, Groningen, Netherlands, ²UMCG, Netherlands, ³MCL,

Leeuwarden, Netherlands. p.arum@umcg.nl

Background: During pregnancy, insulin sensitivity (IS) decreases to ensure nutrient supply to the fetus. Higher pre-pregnancy BMI is linked to decreased IS and increases the risk for gestational diabetes mellitus (GDM), yet early GDM detection is challenging. Therefore, the Pregnancy Outcomes and Maternal Insulin Sensitivity (PROMIS) study aimed to investigate early pregnancy metabolic markers that can predict IS later in pregnancy in overweight women.

Methods:  Thirty women were included in the PROMIS study. Glucose, insulin, and Cpeptide levels were measured in fasted and postprandial blood samples after a meal between week 12-16 (MTT1, n=26), week 24-25 (MTT2, n=21), and week 26-27 (OGTT, n=16) of gestation. IS was calculated using HOMA-IR and the disposition index (DI_o) was calculated as ΔI_0-30/ΔG_0-30*1/fasting insulin.

Results: Postprandial glucose and C-peptide were comparable between MTT1 and MTT2, but higher following OGTT (p<0.001 and 0.005). IS decreased between MTT1 and MTT2 (p=0.001), but was comparable between MTT2 and OGTT. MTT1 fasting insulin, Cpeptide, triglyceride levels and 1h-pp-glucose associated with IS later in pregnancy (r=0.758, p<0.001; r=0.792, p<0.001; r=0.688, p=0.002; and r=0.496, p=0.038 respectively). Fasting C-peptide and triglyceride levels, postprandial glucose, insulin and C-peptide at MTT1 correlated with the 2h-pp-glucose OGTT (r=0.498, p=0.035; r=0.544 p=0.020; r=0.664, p=0.007; r=0.723 p=0.003; and r=0.602, p=0.023 respectively). DI_o during MTT1 did not correlate with postprandial glucose responses during MTT2 and OGTT. We did observe a correlation between 1h-pp-glucose MTT2 and 2h-pp-glucose OGTT (r= 0.633, p=0.009).

Conclusion: Fasting C-peptide and triglyceride levels measured between week 12-16 correlate with IS and glucose responses following an OGTT in week 26-27 of pregnancy. These results suggest that these early second trimester markers might be suitable to stratify women for GDM risk. Finally, the strong correlation between 1h-pp-glucose MTT and the 2h-pp-glucose OGTT supports further exploration of more physiological challenge of the MTT as an alternative for diagnostic purpose.