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© 2005 by the American Diabetes Association, Inc.
Pathophysiology/Complications |
Proinsulin Concentration Is an Independent Predictor of All-Cause and Cardiovascular Mortality
An 11-year follow-up of the Hoorn Study
1 Institute for Research in Extramural Medicine, VU University Medical Center, Amsterdam, the Netherlands
2 Department of General Practice, VU University Medical Center, Amsterdam, the Netherlands
3 Department of Internal Medicine, Academic Hospital Maastricht, Maastricht, the Netherlands
4 Department of Endocrinology, VU University Medical Center, Amsterdam, the Netherlands
Address correspondence and reprint requests to Marjan Alssema, MSc, Institute for Research in Extramural Medicine, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands. E-mail: m.alssema{at}vumc.nl
OBJECTIVE—High proinsulin concentration may be a better predictor for cardiovascular disease (CVD) mortality than insulin concentration. Previous observations may have been confounded by glucose tolerance status or lack of precision because of high intraindividual variability. We investigated the longitudinal relation of means of duplicate measurements of insulin and proinsulin with all-cause and CVD mortality in a population-based cohort taking glucose tolerance status into account.
RESEARCH DESIGN AND METHODS—Fasting and post–75-g glucose-load (2-h) glucose, insulin, and proinsulin values were determined in duplicate on separate days in 277 participants with normal glucose metabolism, 208 participants with impaired glucose metabolism, and 119 newly detected patients with type 2 diabetes of the Hoorn Study. Insulin resistance and ß-cell function were estimated by homeostasis model assessment (HOMA-IR and HOMA-B, respectively), and the fasting proinsulin-to-insulin ratio was calculated. Subjects were followed with respect to mortality until January 2003.
RESULTS—Fasting proinsulin levels were significantly associated with all-cause and CVD mortality. The hazard ratios (HRs) per increase in interquartile range adjusted for age and sex were 1.21 (95% CI 1.04–1.42) for all-cause mortality and 1.33 (1.06–1.66) for CVD mortality. Adjustment for glucose tolerance status and HOMA-IR did not substantially change the associations.
CONCLUSIONS—Fasting proinsulin was associated with all-cause and CVD mortality, independent of glucose tolerance status and insulin resistance and largely independent of other CVD risk factors. Proinsulin might play a role in the relationship between insulin resistance and CVD.
Abbreviations: CVD, cardiovascular disease • HOMA-B, homeostasis model assessment of ß-cell function • HOMA-IR, homeostasis model assessment of insulin resistance • PAI-1, plasminogen activator inhibitor-1
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