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

To identify the primary pathogenic factors involved in the development of T ype 2 diabetes mellitus (DM), we studied Japanese women with former gestati onal diabetes mellitus (CDM) who are at risk for the later development of T ype 2 DM. We used the minimal model analysis derived from frequently sample d intravenous glucose tolerance test (FSIGT). The subjects consisted of eig ht non-obese women with a history of CDM and eight nonobese normal women as control subjects. The 75 g oral glucose tolerance test (75 g OGTT) perform ed within 6 months of delivery confirmed that all the subjects with former GDM had a normal glucose tolerance. Insulin sensitivity (SI) derived from t he minimal model analysis was not different between the two groups. Glucose effectiveness at zero insulin (GEZI), reflecting tissue glucose sensitivit y, 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 phas e insulin secretion found in FSIGT was markedly reduced to 56 % of that obs erved in control subjects (1250 +/- 187.4 vs 2223 +/- 304.3 pmol l(-1) min, p < 0.01). Our results indicate that in former GDM patients, who are Japan ese and non-obese, impairment of the acute insulin response to glucose and a decrease in tissue glucose sensitivity rather than insulin sensitivity ar e the primary pathogenic factors involved. (C) 1998 John Wiley & Sons, Ltd.