Hyperinsulinemia and insulin resistance are independently associated with plasma lipids, uric acid and blood pressure in nondiabetic subjects. The GISIR database

Backgound and Aims: We evaluated whether hyperinsulinemia and/or insulin resistance are independently associated with plasma lipids, uric acid and blood pressure in nondiabetic subjects. Methods and Results: A database of hyperinsulinemic euglycemic clamp carried out with standard technique (40 mU per min per square meter of body surface area) in nondiabetic Italian subjects has been recently established. In this database we evaluated the relationships existing between fasting plasma insulin (FPI), glucose metabolized during clamp (M) and plasma levels of triglycerides (TG), high density lipoprotein cholesterol (HDL-C), uric acid (UA) as well as blood pressure (BP) in nondiabetic subjects with fasting plasma glucose <6.1 mmol/l. Parallel analyses were conducted in all subjects in the database (n=1093) and in those with all variables available (n=309). Results: In the univariate analysis both FPI and M were significantly correlated with TG, HDL-C, UA and BP (systolic, diastolic and mean). Multivariate regression analyses including center, sex, age, body mass index, FPI and M as independent variables showed that: 1) TG and UA were positively correlated with FPI and negatively correlated with M; 2) HDL-C was negatively correlated with FPI and positively correlated with M; 3) BP was negatively correlated with both FPI and M. Analyses of covariance showed that, after adjusting for center, sex, age and BMI, subjects with isolated hyperinsulinemia or isolated insulin resistance had higher TG and UA and lower HDL-C. Subjects with isolated insulin resistance had also higher BP whereas subjects with isolated hyperinsulinemia had lower BP. Subjects with both defects had a worse profile. Conclusions/interpretation: Hyperinsulinemia and insulin resistance might contribute with distinct and independent mechanisms to the development of several metabolic and hemodynamic disorders often clustering in the same individual. In particular, hypertriglyceridemia, low HDL cholesterol and hyperuricemia seem to be related to both hyperinsulinemia and insulin resistance, whereas hypertension seems to be related only to insulin resistance.