Longitudinal changes in insulin sensitivity, insulin secretion, beta cell function and glucose effectiveness during development of non-diabetic hyperglycemia in a Japanese population

Since there had been no previous studies of alterations in insulin sensitivity, glucose-stimulated insulin secretion, beta cell function and glucose effectiveness during the development of non-diabetic hyperglycemia in Asian populations, we conducted a longitudinal study of such changes in 244 Japanese adults with normal glucose tolerance (median BMI 23.3 kg/m(2) and age 51 yrs). The median follow-up period was 3.3 yrs. One hundred and eighty-two subjects maintained normal glucose tolerance (nonprogressors). After excluding the 3 subjects who progressed to diabetes, we analyzed the 59 who developed non-diabetic hyperglycemia (progressors), of which 31 progressed to impaired fasting glucose and 28 to impaired glucose tolerance. Whole body insulin sensitivity was estimated by ISI(Matsuda), glucose-stimulated insulin secretion by [δIRI(0-30)/δPG(0-30)] and Stumvoll indices, hepatic insulin sensitivity by quantitative insulin sensitivity check index (QUICKI) and 1/fasting IRI, beta cell function by oral disposition index (DI(O)) ([δIRI(0-30)/δPG(0-30)]∙[ISI(Matsuda)]), and glucose effectiveness by an OGTT-derived index (SgI(O)). ISI(Matsuda) (p <0.05), [δIRI(0-30)/δPG(0-30)], DI(O) and SgI(O) (both p <0.01), but not QUICKI, 1/fasting IRI, or Stumvoll-1st and -2nd phases, were lower in the progressors at baseline. This group was also characterized by the following: 1) ISI(Matsuda), DI(O) and SgI(O) were reduced by 34%, 32% and 11%, respectively (all p <0.01); 2) QUICKI and 1/fasting IRI diminished by 21% and 5%, respectively (both p <0.01); and 3) no significant changes were found in [δIRI(0-30)/δPG(0-30)], Stumvoll-1st and -2nd phases or BMI during the follow-up. In the nonprogressors, no indices changed significantly during the follow-up. Our study concluded that during the transition from normal glucose tolerance to non-diabetic hyperglycemia in this non-obese population, whole body insulin sensitivity, hepatic insulin sensitivity, beta cell function, and glucose effectiveness were all attenuated, but no significant changes in glucose-stimulated insulin secretion occurred. Also of note is the fact that the transition took place without any accompanying increase in BMI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-3-252) contains supplementary material, which is available to authorized users.