Evaluation of Circulating Determinants of Beta-Cell Function in Women With and Without Gestational Diabetes

Context: Gestational diabetes (GDM) arises in women in whom there is insufficient beta-cell compensation for the insulin resistance of late pregnancy. The mechanisms underlying both normal antepartum beta-cell adaptation and its aberrancy in GDM are unclear. Preclinical studies have suggested that the hormones prolactin and human placental lactogen (HPL) may stimulate beta-cell mass, whereas the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has recently emerged as a potential negative regulator of beta-cell function. However, there has been limited study of these factors in humans. Objective: Our objective was to systematically evaluate HPL, prolactin, and CMPF in relation to glucose homeostasis and beta-cell function in women with and without GDM. Design/Setting/Participants: Three-hundred-and-ninety-five women underwent an oral glucose tolerance test in late pregnancy, enabling assessment of GDM status, glycemia (area-under-the-glucose-curve on oral glucose tolerance test [AUC(glucose)]), beta-cell function (Insulin Secretion-Sensitivity Index-2, insulinogenic index/homeostatic model assessment of insulin resistance [HOMA-IR]), insulin sensitivity/resistance (Matsuda index, HOMA-IR), and circulating HPL, prolactin, and CMPF. Results: Serum concentrations of HPL, prolactin, and CMPF were similar between women with GDM (n = 105) and women without GDM (n = 290). However, on multiple linear regression analyses, CMPF emerged as a significant predictor of AUC(glucose) in women with GDM (t = 4.75, P = .0001) but not in their peers (P = .60). Furthermore, CMPF independently predicted lower Insulin Secretion- Sensitivity Index-2 (t = -2.28, P = .02) and lower insulinogenic index/HOMA-IR (t = -2.22, P = .03) in women with GDM but not in the non-GDM group (both P = .93). Neither HPL nor prolactin was significantly associated with AUCglucose, beta-cell function, or insulin sensitivity. Conclusion: CMPF is a potential circulating determinant of beta-cell dysfunction and hyperglycemia in women with GDM.