Hyperinsulinemia and insulin resistance have been implicated as risk factors for the development of non-insulin-dependent diabetes mellitus (NIDDM). Recent data suggest that proinsulin may comprise a large proportion of immunoreactive insulin in subjects with NIDDM and possibly in those with impaired glucose tolerance (IGT) as well. Increased proinsulin concentrations are thought to be an early indicator of a failing pancreas. We examined proinsulin, insulin (using an assay that does not display appreciable cross-reactivity with proinsulin), and the fasting proinsulin:insulin ratio in 206 nondiabetic Mexican-American (a high-risk population for NIDDM) and 123 nondiabetic non-Hispanic white (a low-risk population for NIDDM) participants in the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Mexican-Americans had significantly higher fasting and 2-h proinsulin and insulin levels but similar fasting proinsulin:insulin ratios compared with non-Hispanic whites. After statistical adjustment for age, body mass index, waist-to-hip ratio, and glucose tolerance status, Mexican-Americans continued to have higher fasting and 2-h insulin and fasting and 2-h proinsulin concentrations but similar proinsulin:insulin ratios compared with non-Hispanic whites. The fasting proinsulin:insulin ratio was higher in 85 subjects with NIDDM compared with subjects with IGT or normal glucose tolerance (0.31, 0.09, and 0.07, respectively). Thus, nondiabetic subjects from a high-risk population for NIDDM are hyperinsulinemic (using an assay that does not cross-react with proinsulin) and, further, do not secrete more proinsulin relative to insulin itself than do nondiabetic subjects from a low-risk population.

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