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.

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.

Subclinical Coronary Atherosclerosis in Asymptomatic Filipino and White Women

“…Our observations are similar to a study of Japanese-Americans, in which proinsulin was not related to CHD. 37 This is the first study to measure EBCT-defined subclinical atherosclerosis among Filipino-Americans; however, some study limitations require acknowledgment. Filipina participants were obtained from a convenience sample of volunteers, whereas white participants were derived from a population-based sample.…”

Proinsulin:insulin and insulin:glucose ratios as predictors of carotid plaque growth: a population-based 7 year follow-up of the Tromsø Study

“…Whether increased proinsulin is simply an indicator of insulin resistance [3], or if it has other proatherogenic actions has been debated [4]. The relationship between proinsulin and CVD has not been fully clarified, and the results of earlier studies are inconsistent [1,5,6]. In some studies, the association between proinsulin and CVD was stronger than that between insulin and CVD [1], and proinsulin has been suggested to have a greater proatherogenic effect than insulin [7].…”

“…However, plaque size and growth are probably just as good or even better markers of atherosclerosis and CHD [10,11]. Most studies that assess proinsulin as a risk factor for CVD include only men [1,[5][6][7]. Furthermore, the relationship between proinsulin or insulin and carotid atherosclerosis has not been explored with a populationbased prospective design.…”

Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of endurance exercise training in non-diabetic whites and blacks: the HERITAGE Family Study

“…Plasma insulin was measured by radioimmunoassay after polyethylene glycol separation [10]. Polyclonal antibodies that cross-react more than 90% with proinsulin, and presumably its conversion intermediates, were used [11,12]. The intra-and interassay coefficients of variation were 7.7 and 10.3%, respectively.…”