The relationships of concentrations of insulin, intact proinsulin and 32?33 split proinsulin with cardiovascular risk factors in Type 2 (non-insulin-dependent) diabetic subjects

Abstract

Standard radioimmunoassay for insulin may substantially overestimate levels of insulin because of cross-reaction with other insulin-like molecules. We have measured concentrations of insulin, intact proinsulin and 32-33 split proinsulin using two-site monoclonal antibody based immunoradiometric assays, and of insulin by a standard radioimmunoassay ("immunoreactive insulin") in 51 Type 2 (non-insulin-dependent) diabetic subjects in the fasting state. The relationships of these concentrations were sought with those of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, plasminogen activator inhibitor, blood pressure, and indices of body fat distribution. Significant relationships were apparent between concentrations of "immunoreactive insulin" as measured by standard radioimmunoassay and triglyceride (rs = 0.42, p less than 0.001), total cholesterol (rs = 0.25, p = 0.038), high density lipoprotein cholesterol (rs = -0.30, p = 0.018) and body mass index (rs = 0.30, p = 0.017), but only the relationships with triglyceride (rs = 0.36, p = 0.006) and body mass index (rs = 0.26, p = 0.34) remained significant when concentrations of immunoradiometrically measured insulin were employed. Concentrations of 32-33 split proinsulin, which comprises the major insulin-like molecule in these subjects, correlated positively with triglyceride (rs = 0.33, p = 0.009), total cholesterol (rs = 0.23, p = 0.050), and plasminogen activator inhibitor (rs = 0.26, p = 0.049), and negatively with high density lipoprotein cholesterol (rs = -0.29, p = 0.021).(ABSTRACT TRUNCATED AT 250 WORDS)

Proinsulin Is an Independent Predictor of Coronary Heart Disease

“…19 This observation further supports that an increase in the concentrations of insulin precursors rather than the plasma insulin concentrations per se underlies the association with CHD. 6 It has been suggested that the association between immunoreactive plasma insulin and CVD may have been confounded by comorbidity in earlier cohort studies. 20 To circumvent such a possibility in the present study, subjects with CVD or malignant disease at baseline were excluded from our analyses.…”

“…Therefore, it has been suggested that increased concentrations of insulin precursor molecules, rather than plasma insulin per se, constitute the association with CHD. 6 The extent to which PLMs contribute to the association between IRI and CHD is largely unknown. In a longitudinal study lasting up to 6.5 years, the significant relationship between proinsulin and CHD became nonsignificant when controlled for the confounding effect of body weight.…”

Hyperinsulinemia, risk factors, and coronary heart disease. The Zutphen Elderly Study.

“…Insulin was measured with a conventional immunoassay known to cross-react with proinsulin. Proinsulin levels are increased in diabetics and subjects with impaired glucose tolerance, 37 and some authors argue that this causes a false observation of an association between hyperinsulinemia and glucose tolerance. However, when proinsulin is taken into account, subjects with impaired glucose tolerance are still shown to have increased insulin concentrations.…”

The Adipocyte and Hemostatic Balance in Obesity

“…27,28 Another possibility is that proinsulin or proinsulin split products, rather than insulin per se, are involved, since NIDDM patients have an elevated basal ratio of plasma proinsulin to immunoreactive insulin and the concentration of PAI-1 in the plasma of these patients correlates more with the concentration of proinsulin and des 29,30 proinsulin than with insulin. 28 Finally, recent observations raise the possibility that insulin resistance rather than hyperinsulinemia may be involved. 29 Obviously, further studies are required to resolve these apparent inconsistencies in the human and animal insulin data.…”