Insulin, proinsulin, proinsulin:insulin ratio, and the risk of developing type 2 diabetes mellitus in women

PURPOSE: To assess the associations among baseline levels of fasting insulin and proinsulin, proinsulin: insulin ratio, and the development of type 2 diabetes mellitus in apparently healthy middle-aged women. METHODS: In a nested case-control study involving a nationwide cohort of 27,628 participants from the Women's Health Study, 126 women with diabetes diagnosed during a 4-year follow-up period were compared with 225 age-matched controls. Fasting insulin level and proinsulin: insulin ratio were assessed in quartiles, and proinsulin level was assessed in categories (less than or equal to4.0 pmol/L, 4.01 to 6.99 pmol/L, greater than or equal to7.0 pmol/L). The risk of developing type 2 diabetes was determined using conditional logistic regression analysis that adjusted for body mass, index and other diabetes risk factors. RESULTS: Baseline insulin and proinsulin levels and proinsulin:insulin ratios were significantly higher among cases than among controls. Women with elevated insulin levels in the highest as compared with the lowest quartile were more likely to develop diabetes (odds ratio [OR] = 5.6; 95% confidence interval [CI]: 1.8 to 17.6), as were women with elevated (greater than or equal to7.0 pmol/L vs. less than or equal to4.0 pmol/L) proinsulin levels (OR = 16.4; 95% CI: 5.8 to 46.8) and women with proinsulin: insulin ratios in the highest quartile (OR = 9.6; 95% CI: 3.1 to 30.8). Similar results were observed among women with a baseline hemoglobin A,. level less than or equal to6.0%. In time-trend analyses, fasting insulin was a consistent predictor of long-term risk. Proinsulin and proinsulin: insulin ratio, although predictive throughout the study, were especially strong predictors of rapid progression to type 2 diabetes. CONCLUSION: Elevated fasting insulin and proinsulin levels and proinsulin:insulin ratio are associated with an increased risk of developing type 2 diabetes in apparently healthy middle-aged women. Am J Med. 2003;114:438-444. (C) 2003 by Excerpta Medica Inc.