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Cross-Sectional and Prospective Associations Between Proinsulin and Cardiovascular Disease Risk Factors in a Population Experiencing Rapid Cultural Transition

¹ Department of Public Health Sciences, University of Toronto, Toronto
² Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto
³ Centre for Studies in Family Medicine, University of Western Ontario
⁴ Robarts Research Institute, London
⁵ Department of Nutritional Sciences and the
⁶ Banting and Best Diabetes Centre, University of Toronto, Toronto
⁷ Departments of Medicine, Biochemistry, and Laboratory Medicine and Pathobiology, St. Michael’s Hospital, University of Toronto, Toronto
⁸ Division of Endocrinology and Metabolism, Mt. Sinai Hospital and University Health Network, Toronto, Ontario, Canada

OBJECTIVE—To examine cross-sectional and prospective associations between proinsulin and cardiovascular disease risk factors using data from a population-based study of type 2 diabetes among Native Canadians.

RESEARCH DESIGN AND METHODS—Between 1993 and 1995, 72% of eligible members of a Native Canadian community participated in a baseline diabetes prevalence survey. Fasting samples were collected for glucose, C-peptide, proinsulin, lipids, and apolipoproteins. A 75-g oral glucose tolerance test was administered, and a second sample for glucose was drawn after 120 min. Blood pressure and waist circumference were determined. In the present study, subjects with normal glucose tolerance (NGT) (n = 505) and impaired glucose tolerance (IGT) (n = 74) were included in cross-sectional analyses. In 1998, 95 individuals who had IGT or NGT at baseline with an elevated 2-h glucose concentration (7.0 mmol/l) participated in a follow-up evaluation using the protocol used at baseline. Cross-sectional and prospective associations between proinsulin and cardiovascular risk factors were assessed using correlation and multiple linear regression analyses.

RESULTS—After adjustment for covariates including age, sex, C-peptide, waist circumference, and glucose tolerance status, fasting proinsulin concentration was significantly associated with concurrently measured lipid and apolipoprotein concentrations (triglycerides: r = 0.18, P < 0.0001; total cholesterol: r = 0.10, P = 0.02; LDL cholesterol: r = 0.11, P = 0.01; HDL cholesterol: r = -0.16, P = 0.0002; apolipoprotein (apo) B: r = 0.17, P < 0.0001; apoAI: r = -0.11, P = 0.008). In the adjusted prospective analysis, baseline triglycerides, HDL cholesterol, and apoB were associated with changes over time in proinsulin (r = 0.23, P = 0.04; r = -0.30, P = 0.01; r = 0.23, P = 0.04; respectively).

CONCLUSIONS—These results confirm previously reported cross-sectional associations between proinsulin and lipid concentrations. In addition, an unexpected association between baseline lipids and proinsulin change was documented.

Abbreviations: apo, apolipoprotein • BP, blood pressure • CVD, cardiovascular disease • FFA, free fatty acid • GTS, glucose tolerance status • IGT, impaired glucose tolerance • NGT, normal glucose tolerance • OGTT, oral glucose tolerance test

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