Volume 42, Number 2, 177-180, DOI: 10.1007/s001250051136

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

J. B. Ruige, J. M. Dekker, G. Nijpels, C. Popp-Snijders, C. D. A. Stehouwer, P. J. Kostense, L. M. Bouter and R. J. Heine

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Abstract

In subjects with impaired glucose tolerance hyperproinsulinaemia has been shown to be predictive for progression to Type II (non-insulin-dependent) diabetes mellitus. These findings are often interpreted as early indicators of an impaired beta-cell function. The aim of our study was to assess the potential determinants of hyperproinsulinaemia in subjects with impaired glucose tolerance. The study group consisted of 110 subjects, 45–74 years of age with mean 2 h plasma glucose concentrations between 8.6 and 11.1 mmol/l following two oral glucose tolerance tests. Subsequently, the hyperglycaemic clamp technique (10 mmol/l, with a priming infusion of 20 % glucose solution, 150 mg/kg) was used to assess the beta-cell function (time needed to reach the insulin peak) and insulin sensitivity (M/I value: glucose metabolised divided by insulin response, 150–180 min). Results showed that the intact-proinsulin:insulin ratio increased with increasing time needed to reach the insulin peak (0.065, 0.079 and 0.101; time needed to reach the insulin peak ≤ 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 function in a study group of subjects with impaired glucose tolerance selected after two oral glucose tolerance tests. [Diabetologia (1999) 42: 177–180]

Keywords Impaired glucose tolerance - insulin - proinsulin - hyperglycaemic clamp - beta-cell function - insulin sensitivity.

Received: 5 June 1998 and in final revised form: 5 October 1998

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