Beta cell dysfunction and its clinical significance in gestational diabetes

Abstract

Pancreatic beta cells compensate for changes in whole body insulin sensitivity through an increase in insulin secretion. The relationship between insulin sensitivity and insulin secretion is characterized by a rectangular hyperbolic function, such that the product of the two variables, termed as the disposition index, should yield a constant for a given degree of glucose tolerance [1][2]. Although beta cell dysfunction and insulin resistance may occur independently, the disposition index typically decreases through the progression from normal glucose toler- abstract. The aim of this study is to explore beta cell dysfunction and its clinical significance in gestational diabetes mellitus (GDM). We assessed insulin sensitivity and insulin secretion in a total of 277 Japanese women between 24 and 27 weeks of pregnancy who underwent a 2 h, 75 g oral glucose tolerance test (OGTT) because of an abnormal result on a 1 h 50 g oral glucose challenge conducted as part of a standard screening for GDM. Insulin sensitivity was evaluated by an insulin sensitivity index derived from OGTT (IS OGTT ), whereas insulin secretion was calculated as a ratio of the total area under the insulin curve to the total area under the glucose curve (AUC ins/glu ). Beta cell function in relation to insulin sensitivity (i.e. disposition index) was derived from the product of insulin sensitivity and insulin secretion (i.e. AUC ins/glu × IS OGTT ). In women diagnosed with GDM (n=57), the disposition index was significantly lower than that in those without GDM, irrespective of obesity. The disposition index in women with GDM was significantly correlated with levels of fasting and mean preprandial capillary glucose and HbA1c before initiating insulin therapy (r = -0.45, -0.38, -0.49, respectively). Furthermore, there was a significant correlation between the disposition index and total insulin dosage to achieve glycemic goal (r = -0.41). In conclusion, we demonstrated beta cell dysfunction in Japanese women with GDM irrespective of obesity. The level of beta cell dysfunction in GDM was associated with the severity of glucose intolerance and total insulin dosage required. These findings underpin clinical significance of beta cell dysfunction in GDM.

The expression of genes involved in NF-κB activation in peripheral blood mononuclear cells of patients with gestational diabetes

“…The patients who developed GDM in the 3rd trimester also had significantly higher HOMA-IR, which emphasizes the role of increased insulin resistance against the background of enormous tissue insulin demands in the development of late-onset GDM. Our findings are consistent with the results of other studies (44,45,46) showing unchanged AUC Ins /AUC Glu index, but an inadequate insulin compensation for decreased insulin sensitivity in women with GDM. We should also mention that the number of patients with a normal OGTT result at the 1st visit, but later diagnosed as having GDM, was much higher than expected.…”

Clinical impact of women with gestational diabetes mellitus by the new consensus criteria: two year experience in a single institution in Japan

“…With respect to beta cell function, levels of ISSI-2 in women with 2/3-AV were significantly lower than those with 1-AV. The level of beta cell function is associated with the severity of glucose intolerance in GDM [9]. Additionally, our previous investigation demonstrated that beta cell dysfuntion in women with 2/3-AV appeared more severe than those with 1-AV [10].…”

Association of common polymorphisms with gestational diabetes mellitus in Japanese women: A case-control study

“…It is well known that an impaired insulin secretion plays a critical role in the development of T2DM or GDM in east Asian including Japanese [24,25]. Therefore, most of SNPs analyzed were insulin secretion candidate SNPs.…”