Hyperproinsulinaemia in impaired glucose tolerance is associated with a delayed insulin response to glucose

In subjects with impaired glucose tolerance hyperproinsulinaemia has been s hown to be predictive for progression to Type II (non-insulin-dependent) di abetes mellitus. These findings are often interpreted as early indicators o f an impaired beta-cell function. The aim of our study was to assess the po tential determinants of hyperproinsulinaemia in subjects with impaired gluc ose tolerance. The study group consisted of 110 subjects, 45-74 years of ag e with mean 2 h plasma glucose concentrations between 8.6 and 11.1 mmol/l f ollowing two oral glucose tolerance tests. Subsequently, the hyperglycaemic clamp technique (10 mmol/l, with a priming infusion of 20% glucose solutio n, 150 mg/kg) was used to assess the beta-cell function (time needed to rea ch the insulin peak) and insulin sensitivity (M/I value: glucose metabolise d divided by insulin response, 150-180 min). Results showed that the intact -proinsulin:insulin ratio increased with increasing time needed to reach th e insulin peak (0.065, 0.079 and 0.101; time needed to reach the insulin pe ak less than or equal to 5 min, 5 to 15 min, >15 min; p < 0.05). The split- proinsulin:insulin ratio showed a similar association with the time needed to reach the insulin peak. These associations were independent of age, sex, body mass index and waist:hip ratio. In conclusion, this study shows that relative hyperproinsulinaemia is associated with an impaired beta-cell func tion in a study group of subjects with impaired glucose tolerance selected after two oral glucose tolerance tests.