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Cross-Sectional and Prospective Associations between Abdominal Adiposity and Proinsulin Concentration

Department of Public Health Sciences (A.J.G.H., G.M.-E.), University of Toronto, Ontario M5S 1A8; Samuel Lunenfeld Research Institute (A.J.G.H., B.Z.), Mt. Sinai Hospital, Toronto, Ontario M5S 1X5; Centre for Studies in Family Medicine (S.B.H.), University of Western Ontario, London, Ontario N6G 4X8; Robarts Research Institute (R.A.H.), London, Ontario N6A 5K8; Department of Nutritional Sciences (T.M.S.W.), University of Toronto, Ontario M5S 1A8; Banting and Best Diabetes Centre (J.K.), University of Toronto, Ontario M5G 2C4; and Division of Endocrinology and Metabolism (B.Z.), Mt. Sinai Hospital and the University Health Network, Toronto, Ontario M5G 1X5

Address all correspondence and requests for reprints to: Anthony Hanley, Ph.D., Division of Epidemiology and Biostatistics, Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, 600 University Avenue, Room 843, Toronto, Ontario, M5G 1X5, Canada. E-mail: hanley{at}mshri.on.ca

The objective of this study was to investigate the associations of total and abdominal obesity with variation in proinsulin concentration in a Native Canadian population experiencing an epidemic of type 2 diabetes mellitus (DM).

Between 1993 and 1995, 728 members of a Native Canadian community participated in a population-based survey to determine the prevalence and risk factors for type 2 DM. Samples for glucose, C-peptide, and proinsulin were drawn after an overnight fast, and a 75-g oral glucose tolerance test was administered. Type 2 DM and impaired glucose tolerance (IGT) were diagnosed using World Health Organization criteria. Height, weight, waist circumference, and percent body fat were measured. In 1998, 95 individuals who, at baseline, had IGT or normal glucose tolerance with an elevated 2-h glucose level (7.0 mM) participated in a follow-up evaluation using the same protocol.

After adjustment for age, sex, C-peptide concentration, per cent body fat, and waist circumference, proinsulin was found to be significantly elevated in diabetic subjects, relative to subjects with both impaired and normal glucose tolerance (both P < 0.0001); and the concentration in those with IGT was higher, compared with normals (P < 0.0001). Among nondiabetic subjects, proinsulin showed significant univariate associations with percent body fat, body mass index, and waist circumference (r = 0.34, 0.45, 0.41, respectively, all P < 0.0001). After adjustment for body fat and other covariates, waist circumference remained significantly associated with proinsulin concentration in nondiabetic subjects (r = 0.20, P < 0.0001). In prospective analysis, adjusted for covariates (including baseline IGT and follow-up glucose tolerance status), baseline waist circumference was positively associated with both follow-up and change in proinsulin concentration (r = 0.27, P = 0.01; r = 0.24, P = 0.03, respectively).

These data highlight the detrimental effects of abdominal obesity on ß-cell function, and support the hypothesis that ß-cell dysfunction occurs early in the natural history of glucose intolerance.

This work was supported by grants from the NIH (91-DK-01 and 1-R21-DK-44597-01) and the Ontario Ministry of Health (04307). A.J.G.H. was supported by Health Canada through a National Health Research and Development Programme Research Training Award, and is currently supported through a Post-Doctoral training award of the Canadian Institutes of Health Research. S.B.H. is a Career Scientist with the Ontario Ministry of Health. R.A.H. is a Career Investigator of the Heart and Stroke Foundation of Ontario (no. 2729).

Abbreviations: BIA, Bioelectrical impedance analysis; BMI, body mass index; CI, confidence interval; DM, diabetes mellitus; GTS, glucose tolerance status; IAF, intraabdominal fat; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; PI/I, proinsulin-to-insulin ratio; WHO, World Health Organization; WHR, waist to hip ratio.

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