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Recent data suggest that proinsulin may be associated with increased cardiovascular risk factors in both diabetic and nondiabetic subjects. We examined the relation of insulin, proinsulin, and the fasting proinsulin/insulin ratio to a number of metabolic disorders believed to be related to the insulin resistance syndrome (low high density lipoprotein cholesterol and high triglyceride levels, hypertension, and impaired glucose tolerance). Proinsulin was measured by a RIA, and insulin was measured by a Linco RIA that does not cross-react with proinsulin. The increased fasting proinsulin/insulin ratio was significantly associated with hypertension, low high density lipoprotein cholesterol and high triglyceride levels, and impaired glucose tolerance in 423 nondiabetic subjects. The fasting proinsulin/insulin ratio increased significantly with the number of metabolic disorders (zero, 0.060; one, 0.086; two, 0.098; three, 0 …