To investigate the metabolic adaptation of normal pregnancy and the pathogenesis of gestational diabetes mellitus (GDM) from the first to the third trimester.

This was a case-control study. A total of 1 471 pregnant women who visited at the Department of Obstetrics of Peking University First Hospital in the first trimester from September 2017 to June 2018. Those with complete serum samples in the first, second and third trimester and who delivered in the hospital were taken as research objects. They were divided into a GDM group and a normal control group according to their glucose metabolism status. Fasting plasma glucose (FPG) and fasting insulin (FINS) in first, second and third trimester were detected, and 75 g oral glucose tolerance test (OGTT) was performed at 24 weeks and later to explore metabolic adaptation in pregnancy and the pathogenesis of GDM. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were calculated. T-test and Mann-Whitney U test were used to compare between groups.

A total of 510 subjects were included in the study. There were 260 cases in GDM group and 250 cases in normal control group. In terms of blood glucose, FPG, 1 h-postprandial plasma glucose (1hPG) and 2 h-postprandial plasma glucose (2hPG) of 75g OGTT in GDM group were significantly higher than those in control group [5.14 (4.80, 5.34) vs 4.63 (4.43, 4.84), 9.56 (8.17, 10.48) vs 7.64 (6.57, 8.63), 8.05 (6.88, 9.08) vs 6.46 (5.82, 7.22) mmol/L,P<0.001]. The level of FPG in both GDM and normal control groups decreased gradually with gestational age (FPG of different trimesters were all P<0.017), but the level of FPG in GDM group was significantly higher than that in control group from first to third trimester[5.27 (4.99, 5.55) vs 5.10 (4.87, 5.30), 5.14 (4.80, 5.34) vs 4.63 (4.43, 4.84),4.77 (4.52, 5.08) vs 4.48 (4.31, 4.70) mmol/L, P<0.001]. In terms of insulin resistance and dynamic changes in islet beta cell function, all FINS levels, HOMA-IR and HOMA-β increased gradually from the first to the third trimester, peaking in the third trimester, whether GDM or normal control group. FINS in the second trimester and HOMA-IR from the first to the third trimester in GDM group were higher than those in control group (all P<0.05), whereas HOMA-β in the second and the third trimesters were lower than those in control group (all P<0.001).

Physiological insulin resistance occurs in normal pregnancy, and beta cells compensate to maintain normal blood glucose. However, there was more severe insulin resistance and higher FPG in GDM group from the first trimester, and beta cell insufficiency in the second and third trimesters. It is suggested that although GDM is diagnosed in second trimester and later, its pathological and physiological abnormalities are already present in the first trimester.

Diabetes, gestational; Metabolic adaptation; Insulin resistance; β cell compensation