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American Journal of Epidemiology Vol. 155, No. 9 : 834-841
Copyright © 2002 by The Johns Hopkins University School of Hygiene and Public Health

ORIGINAL CONTRIBUTIONS

Hyperproinsulinemia and Proinsulin-to-Insulin Ratios in Swedish Middle-aged Men: Association with Glycemia and Insulin Resistance but Not with Family History of Diabetes

V. Grill1,,2, B. Dinesen3, S. Carlsson4, S. Efendic1, O. Pedersen3 and C.-G. Östenson1

1 Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
2 Department of Medicine, Endocrinology Section, University Hospital of Trondheim, Trondheim, Norway.
3 Steno Diabetes Center, Gentofte, Denmark.
4 Division of Epidemiology, Karolinska University Hospital, Stockholm, Sweden.

Elevated proinsulin and proinsulin/insulin ratios are features of abnormal ß-cell function in type 2 diabetes. The participation of genetic factors is disputed. The authors wished to investigate relations between family history of diabetes on one hand and proinsulin as well as proinsulin/immunoreactive insulin ratios on the other. A large, population-based sample of Swedish men aged 35–54 years in 1992 was studied. Subjects without known diabetes were selected either to have a strong family history of diabetes (n = 1,619) or no history of the disease (n = 1,495). An oral glucose tolerance test detected 172 subjects with impaired glucose tolerance and 55 subjects with previously unknown diabetes according to World Health Organization 1985 criteria. In multiple regression analysis, fasting levels of proinsulin and proinsulin/insulin ratios were positively associated both with the 2-hour glucose level (as a continuous variable) and with obesity, whereas a negative association was found with birth weight. No association was found with family history of diabetes or with chronologic age. These findings indicate that elevated proinsulin and proinsulin/insulin ratios are secondary to increased demands on ß-cell secretion induced by hyperglycemia and insulin resistance with no discernible influence of family history of diabetes.

birth weight; diabetes mellitus; non-insulin-dependent; glucose intolerance; insulin; insulin intolerance; obesity; proinsulin

Abbreviations: BMI, body mass index; IGT, impaired glucose tolerance; IRI, immunoreactive insulin; OGTT, oral glucose tolerance test; P/IRI, proinsulin/immunoreactive insulin; WHO, World Health Organization


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