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Relationship of proinsulin and insulin with noninsulin-dependent diabetes mellitus and coronary heart disease in Japanese-American men: impact of obesity--clinical research center study.
J Clin Endocrinol Metab. 1995 Apr; 80(4):1399-406.JC

Abstract

Obesity is associated with noninsulin-dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD), and these interactions have usually been related to changes in immunoreactive insulin (IRI) levels. A role of proinsulin (PI) in this association has been suggested. We, therefore, examined IRI, PI, and true insulin levels and the PI/IRI ratio by glucose tolerance or CHD status in a cross-sectional study of 170 Japanese-American men (45-74 yr old) in whom 2 measures of adiposity (body mass index and intraabdominal fat) were made to assess potential associations in this population with a high prevalence of both NIDDM and CHD. Subjects were classified as having normal glucose tolerance (n = 58), impaired glucose tolerance (IGT; n = 55), or NIDDM (n = 57) or were classified by CHD status (without CHD, n = 127; with CHD, n = 43). A positive linear relationship existed between obesity, determined either as the body mass index or intraabdominal fat, and IRI, PI, and true insulin, but not the PI/IRI ratio. In the NIDDM subjects, PI levels were disproportionately greater than those in subjects with normal glucose tolerance or IGT, so the PI/IRI ratio was significantly greater in the NIDDM group [mean (95% confidence interval): normal glucose tolerance, 11.8% (range, 10.4-13.5); IGT, 12.8% (range, 10.8-15.1); NIDDM, 19.2% (range, 15.4-24.0); P = 0.0002] even when adjusted for obesity (P = 0.0004). In subjects with CHD compared to subjects without CHD, IRI (P = 0.0026) and true insulin levels (P = 0.0043) were increased, but PI levels were not. However, these differences were not present after adjustment for obesity. In contrast, when intraabdominal fat was adjusted for IRI or true insulin, a significant effect of intraabdominal fat on CHD risk was maintained (P = 0.045 and P = 0.029, respectively), suggesting that another factor(s) associated with central obesity may be involved in CHD risk. Thus, in Japanese-American men, elevated PI and PI/IRI ratio are markers of B-cell dysfunction, and these are not the result of obesity. An elevated true insulin level is present in those with CHD, but this appears to be the result of obesity. In contrast, central adiposity confers an additional risk for CHD independent of insulin.

Authors+Show Affiliations

Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7714116

Citation

Kahn, S E., et al. "Relationship of Proinsulin and Insulin With Noninsulin-dependent Diabetes Mellitus and Coronary Heart Disease in Japanese-American Men: Impact of Obesity--clinical Research Center Study." The Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 4, 1995, pp. 1399-406.
Kahn SE, Leonetti DL, Prigeon RL, et al. Relationship of proinsulin and insulin with noninsulin-dependent diabetes mellitus and coronary heart disease in Japanese-American men: impact of obesity--clinical research center study. J Clin Endocrinol Metab. 1995;80(4):1399-406.
Kahn, S. E., Leonetti, D. L., Prigeon, R. L., Boyko, E. J., Bergstrom, R. W., & Fujimoto, W. Y. (1995). Relationship of proinsulin and insulin with noninsulin-dependent diabetes mellitus and coronary heart disease in Japanese-American men: impact of obesity--clinical research center study. The Journal of Clinical Endocrinology and Metabolism, 80(4), 1399-406.
Kahn SE, et al. Relationship of Proinsulin and Insulin With Noninsulin-dependent Diabetes Mellitus and Coronary Heart Disease in Japanese-American Men: Impact of Obesity--clinical Research Center Study. J Clin Endocrinol Metab. 1995;80(4):1399-406. PubMed PMID: 7714116.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relationship of proinsulin and insulin with noninsulin-dependent diabetes mellitus and coronary heart disease in Japanese-American men: impact of obesity--clinical research center study. AU - Kahn,S E, AU - Leonetti,D L, AU - Prigeon,R L, AU - Boyko,E J, AU - Bergstrom,R W, AU - Fujimoto,W Y, PY - 1995/4/1/pubmed PY - 1995/4/1/medline PY - 1995/4/1/entrez SP - 1399 EP - 406 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 80 IS - 4 N2 - Obesity is associated with noninsulin-dependent diabetes mellitus (NIDDM) and coronary heart disease (CHD), and these interactions have usually been related to changes in immunoreactive insulin (IRI) levels. A role of proinsulin (PI) in this association has been suggested. We, therefore, examined IRI, PI, and true insulin levels and the PI/IRI ratio by glucose tolerance or CHD status in a cross-sectional study of 170 Japanese-American men (45-74 yr old) in whom 2 measures of adiposity (body mass index and intraabdominal fat) were made to assess potential associations in this population with a high prevalence of both NIDDM and CHD. Subjects were classified as having normal glucose tolerance (n = 58), impaired glucose tolerance (IGT; n = 55), or NIDDM (n = 57) or were classified by CHD status (without CHD, n = 127; with CHD, n = 43). A positive linear relationship existed between obesity, determined either as the body mass index or intraabdominal fat, and IRI, PI, and true insulin, but not the PI/IRI ratio. In the NIDDM subjects, PI levels were disproportionately greater than those in subjects with normal glucose tolerance or IGT, so the PI/IRI ratio was significantly greater in the NIDDM group [mean (95% confidence interval): normal glucose tolerance, 11.8% (range, 10.4-13.5); IGT, 12.8% (range, 10.8-15.1); NIDDM, 19.2% (range, 15.4-24.0); P = 0.0002] even when adjusted for obesity (P = 0.0004). In subjects with CHD compared to subjects without CHD, IRI (P = 0.0026) and true insulin levels (P = 0.0043) were increased, but PI levels were not. However, these differences were not present after adjustment for obesity. In contrast, when intraabdominal fat was adjusted for IRI or true insulin, a significant effect of intraabdominal fat on CHD risk was maintained (P = 0.045 and P = 0.029, respectively), suggesting that another factor(s) associated with central obesity may be involved in CHD risk. Thus, in Japanese-American men, elevated PI and PI/IRI ratio are markers of B-cell dysfunction, and these are not the result of obesity. An elevated true insulin level is present in those with CHD, but this appears to be the result of obesity. In contrast, central adiposity confers an additional risk for CHD independent of insulin. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/7714116/Relationship_of_proinsulin_and_insulin_with_noninsulin_dependent_diabetes_mellitus_and_coronary_heart_disease_in_Japanese_American_men:_impact_of_obesity__clinical_research_center_study_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.80.4.7714116 DB - PRIME DP - Unbound Medicine ER -