Defects in Insulin Secretion and Action in Women With a History of Gestational Diabetes

Abstract

Gestational diabetes mellitus (GDM) is associated with defects in insulin secretion and insulin action, and women with a history of GDM carry a high risk for the development of non-insulin-dependent diabetes mellitus (NIDDM). Assessment of subjects with a history of GDM who are currently normoglycemic should help elucidate some of the underlying defects in insulin secretion or action in the evolution of NIDDM. We have studied 14 women with normal oral glucose tolerance who had a history of GDM. They were compared with a group of control subjects who were matched for both body mass index (BMI) and waist-to-hip ratio (WHR). All subjects underwent tests for the determination of oral glucose tolerance, ultradian oscillations in insulin secretion during a 28-h glucose infusion, insulin secretion in response to intravenous glucose, glucose disappearance after intravenous glucose (Kg), and insulin sensitivity (SI) as measured by the Bergman minimal model method. The BMI in the post-GDM women was similar to that in the control subjects (24.9 +/- 1.2 vs. 25.4 +/- 1.4 kg/m2, respectively), as was the WHR ratio (0.80 +/- 0.01 vs. 0.76 +/- 0.01, respectively). The post-GDM women were slightly older (35.2 +/- 0.9 vs. 32.1 +/- 1.4 years, P = 0.04). The fasting plasma glucose levels were significantly higher in the post-GDM group than in the control group (4.9 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, respectively, P < 0.001) and remained higher at each of the subsequent determinations during the oral glucose tolerance test, although none had a result indicative of either diabetes or impaired glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes

“…Abnormalities in beta cell function as well as in insulin action have been described in other cohorts of women with a history of gestational diabetes [15,[37][38][39][40][41][42]. The heterogeneity between these studies is probably a result of the different ethnic and geographic origins of the populations studied.…”

Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population

“…It was found that the transgenic expression of the gene encoding menin in maternal beta cells inhibited islet expansion and led to the development of GDM phenotypes [35]. In human studies, inadequate compensatory insulin secretion in the face of increased insulin resistance has consistently been observed in patients with GDM [36][37][38]. In this regard, the risk alleles of rs7756992 and rs7754840 in CDKAL1 and rs10811661 in CDKN2A-CDKN2B may play crucial roles in the pathogenesis of GDM through impaired compensatory insulin secretion by pancreatic beta cells.…”

Targeting beta-cell preservation in the management of type 2 diabetes

“…It can be seen in patients with IGT, 41 in normoglycaemic women with a history of gestational diabetes 42 and in normoglycaemic first-degree relatives of patients with T2D. 43 The magnitude of first-phase insulin release inversely correlates with the degree of beta-cell dysfunction.…”