DISPROPORTIONATELY INCREASED PROINSULIN LEVELS ARE WITH THE INSULIN-RESISTANCE SYNDROME

Recent data suggest that proinsulin may be associated with increased c ardiovascular risk factors in both diabetic and nondiabetic subjects. We examined the relation of insulin, proinsulin, and the fasting proin sulin/insulin ratio to a number of metabolic disorders believed to be related to the insulin resistance syndrome (low high density lipoprote in cholesterol and high triglyceride levels, hypertension, and impaire d glucose tolerance). Proinsulin was measured by a RIA, and insulin wa s measured by a Linco RIA that does not cross-react with proinsulin. T he increased fasting proinsulin/insulin ratio was significantly associ ated with hypertension, low high density lipoprotein cholesterol and h igh triglyceride levels, and impaired glucose tolerance in 423 nondiab etic subjects. The fasting proinsulin/insulin ratio increased signific antly with the number of metabolic disorders (zero, 0.060; one, 0.086; two, 0.098; three, 0.177; four, 0.182; P < 0.001). The increased proi nsulin/insulin ratio was also associated with a greater number of meta bolic disorders in diabetic subjects. Our results show that particular ly nondiabetic individuals with the insulin resistance syndrome not on ly have hyperinsulinemia as a marker of insulin resistance, but also s how an increase in proinsulin relative to insulin, which may reflect r elative beta-cell failure or malfunction.