PROINSULIN AND SPECIFIC INSULIN CONCENTRATION IN HIGH-RISK AND LOW-RISK POPULATIONS FOR NIDDM

Hyperinsulinemia and insulin resistance have been implicated as risk f actors for the development of non-insulin-dependent diabetes mellitus (NIDDM). Recent data suggest that proinsulin may comprise a large prop ortion of immunoreactive insulin in subjects with NIDDM and possibly i n those with impaired glucose tolerance (IGT) as well. increased proin sulin concentrations are thought to be an early indicator of a failing pancreas. We examined proinsulin, insulin (using an assay that does n ot display appreciable cross-reactivity with proinsulin), and the fast ing proinsulin:insulin ratio in 206 nondiabetic Mexican-American (a hi gh-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 diseas e, Mexican-Americans had significantly higher fasting and 2-h proinsul in and insulin levels but similar fasting proinsulin:insulin ratios co mpared with non-Hispanic whites. After statistical adjustment for age, body mass index, waist-to-hip ratio, and glucose tolerance status, Me xican-Americans continued to have higher fasting and 2-h insulin and f asting and 2-h proinsulin concentrations but similar proinsulin:insuli n ratios compared with non-Hispanic whites. The fasting proinsulin:ins ulin ratio was higher in 85 subjects with NIDDM compared with subjects with IGT or normal glucose tolerance (0.31, 0.09, and 0.07, respectiv ely). Thus, nondiabetic subjects from a high-risk population for NIDDM are hyperinsulinemic (using an assay that does not crossreact with pr oinsulin) and, further, do not secrete more proinsulin relative to ins ulin itself than do nondiabetic subjects from a low-risk population.