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

Obesity is associated with noninsulin-dependent diabetes mellitus (NID DM) and coronary heart disease (CHD), and these interactions have usua lly been related to changes in immunoreactive insulin (IRI) levels. A role of proinsulin (PI) in this association has been suggested. We, th erefore, examined IRI, PI, and true insulin levels and the PI/IRI rati o 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) o r were classified by CHD status (without CHD, n = 127; with CHD, n = 4 3). 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 lev els were disproportionately greater than those in subjects with normal glucose tolerance or IGT, so the PI/IRI ratio was significantly great er 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); NI DDM, 19.2% (range, 15.4-24.0); P = 0.00021 even when adjusted for obes ity (P = 0.0004). In subjects with CHD compared to subjects without CH D, IRI (P = 0.0026) and true insulin levels (P = 0.0043) were increase d, but PI levels were not. However, these differences were not present after adjustment for obesity. In contrast, when intraabdominal fat wa s adjusted for IRI or true insulin, a significant effect of intraabdom inal fat on CHD risk was maintained (P = 0.045 and P = 0.029, respecti vely), suggesting that another factor(s) associated with central obesi ty may be involved in CHD risk. Thus, in Japanese-American men, elevat ed PI and PI/IRI ratio are markers of B-cell dysfunction, and these ar e 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 c ontrast, central adiposity confers an additional risk for CHD independ ent of insulin.