No deterioration in insulin sensitivity, but impairment of both pancreatic β-cell function and glucose sensitivity, in Japanese women with former gestational diabetes mellitus

Abstract

To identify the primary pathogenic factors involved in the development of Type 2 diabetes mellitus (DM), we studied Japanese women with former gestational diabetes mellitus (GDM) who are at risk for the later development of Type 2 DM. We used the minimal model analysis derived from frequently sampled intravenous glucose tolerance test (FSIGT). The subjects consisted of eight non-obese women with a history of GDM and eight non-obese normal women as control subjects. The 75 g oral glucose tolerance test (75 g OGTT) performed within 6 months of delivery confirmed that all the subjects with former GDM had a normal glucose tolerance. Insulin sensitivity (SI) derived from the minimal model analysis was not different between the two groups. Glucose effectiveness at zero insulin (GEZI), reflecting tissue glucose sensitivity, was significantly lower in former GDM patients than in control subjects (1.18+/-0.34 vs 2.26+/-0.29 x 10(-2) min(-1), p < 0.05). The early phase insulin secretion found in FSIGT was markedly reduced to 56% of that observed in control subjects (1250+/-87.4 vs 2223+/-304.3 pmol l(-1) min, p < 0.01). Our results indicate that in former GDM patients, who are japanese and non-obese, impairment of the acute insulin response to glucose and a decrease in tissue glucose sensitivity rather than insulin sensitivity are the primary pathogenic factors involved.

Value of the intravenous and oral glucose tolerance tests for detecting subtle impairments in insulin sensitivity and beta‐cell function in former gestational diabetes

“…Our results are in agreement with those of some previous studies, 7,8,32 where AIR was not different in a group of normotolerant fGDM women compared to control subjects of similar age and BMI. In other studies, 4,12 AIR was lower in normotolerant fGDM.…”

“…Even greater differences have been observed for betacell function. Insulin secretion has been found impaired, [1][2][3][4][5][6]8,12 normal, 7,9,11,13 and even increased. 10 A possible reason for these different findings is that several investigations included subjects with different glucose tolerance studied as a group.…”

Impaired β‐cell function in lean normotolerant former gestational diabetic women

“…Insulin sensitivity and secretion in fGDM have been assessed in numerous studies [24–32], which have shown the presence of insulin resistance and impaired β‐cell function. Many of these studies, however, have focused on insulin sensitivity rather than β‐cell function, and are not directly comparable with our work, as the typical fGDM population includes obese, insulin‐resistant and possibly glucose intolerant subjects [24–27].…”

Lispro Is Superior to Regular Insulin in Transient Intensive Insulin Therapy in Type 2 Diabetes

“…The view, however, that multiple insulin injections are desirable for type 2 diabetes is not common in Western countries (26,27), because among other reasons, it is feared that exogenous insulin will promote weight gain. In Japanese, however, weight gain is less of a concern, and diminished insulin secretion appears to be the pivotal event, making this population particularly vulnerable to the deleterious effects of insulin resistance (28)(29)(30). In other words, Japanese subjects may be more prone to develop 'insulinopenia' with less provocation than Westerners.…”