Insulin Sensitivity, Islet Cell Function, and Incretin Axis in Pregnant Women With and Without Gestational Diabetes Mellitus

Indian J Endocrinol Metab. 2024 Jan-Feb;28(1):71-79. doi: 10.4103/ijem.ijem_7_23. Epub 2024 Feb 26.

Abstract

Introduction: The aim of this study was to compare insulin sensitivity, islet cell function, and incretin axes in pregnant subjects with GDM and normal healthy controls.

Methods: Pregnant women at 24 to 28 weeks of gestation were subjected to a 75 g oral glucose tolerance test (OGTT). Samples for glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were collected at 0, 30, 60, and 120 min during the OGTT. The Matsuda index (MI) and insulin secretion and sensitivity index-2 (ISSI-2) were assessed. The glucagon suppression index (GSI) was calculated along with the area under the curve (AUC) for glucose, insulin, glucagon, GLP-1, and GIP.

Results: A total of 48 pregnant women (25 GDM and 23 controls) were finally analysed. The MI and ISSI-2 were low in the GDM group [4.31 vs. 5.42; P = 0.04], [1.99 vs. 3.18, P ≤ 0.01] respectively). Total AUCglucagon was higher in the GDM group (7411.7 vs. 6320.1, P = 0.02). GSI30 was significantly lower in the GDM group (-62.6 vs. -24.7, P = 0.03). Fasting GLP-1 levels were low in GDM women (17.3 vs. 22.2, P = 0.04). The total AUCGLP-1 positively correlated with total GSI in the GDM group.

Conclusion: Asian-Indian GDM women have high insulin insensitivity, islet cell dysfunction, and low fasting GLP-1. Incretin axis dysfunction plays a potential role in their islet cell dysfunction.

Keywords: Alpha cell; beta cell; diabetes in pregnancy; glucagon; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; insulin secretion and sensitivity index-2.