Aims: Our objective was to examine prospectively the associations between fasting plasma proinsulin and the proinsulin/insulin ratio and the incidence of Type 2 diabetes in women.
Subjects and methods: We designed a nested case-control study within the Nurses' Health Study, a cohort of 121,700 US women aged 30-55 years at study inception in 1976. Fasting plasma proinsulin, specific insulin and C-peptide levels were determined in 183 women with a new diagnosis of diabetes made after blood sampling between 1989 and 1990, and 369 control subjects without diabetes.
Results: After adjustment for age, body mass index, family history of diabetes and other potential confounders, including HbA1c, the odds ratios for diabetes associated with increasing quartiles of proinsulin were 1.00, 0.85, 2.49 and 5.73 (P for trend: < 0.001). Proinsulin remained significantly associated with diabetes risk after adjusting for C-peptide and specific insulin (multivariate odds ratios for quartiles: 1.00, 0.78, 1.94, 3.69; P for trend = 0.001). In addition, the proinsulin/insulin ratio was significantly associated with diabetes risk, controlling in multivariate analysis for C-peptide (odds ratios for extreme quartiles: 2.48; 95% CI: 1.14-5.41; P for trend = 0.005).
Conclusions: These data suggest that proinsulin and the proinsulin/insulin ratio are strong independent predictors of diabetes risk, after adjustment for obesity and other potential confounders.