Differential Predictors of Insulin Resistance in Nondiabetic Salt-Resistant and Salt-Sensitive Subjects

Abstract

We studied the characteristics of insulin resistance in 19 normotensive and 25 hypertensive subjects who underwent an acute protocol for determination of salt-sensitivity of blood pressure. Hypertensive subjects were older and more obese, with higher creatinine, lipids, and aldosterone than normotensive volunteers. They also had higher glucose and insulin levels with a marked decrease in insulin sensitivity (HOMA2-S index). Once all participants were classified into salt-sensitive (SS) and salt-resistant (SR) groups, most of these differences were no longer present. In contrast, SS had classical characteristics of this phenotype (higher percentage of blacks, suppressed plasma renin, increased aldosterone-to-renin ratio, and blunted renin and aldosterone responses to changes in salt balance). Despite similar insulin levels, HOMA2-S was significantly lower in SS than SR. Salt-loading did not change HOMA2-S in SS or SR. In contrast, salt-depletion, by significantly increasing glucose and insulin of SR, decreased their HOMA2-S to the levels observed in SS. Correlates of insulin resistance in SR included age, triglycerides, body mass index, mean arterial pressure, aldosterone, and epinephrine. However, only body mass index and aldosterone remained as significant predictors in multivariate analyses. Correlates of insulin resistance in SS were mean arterial pressure, epinephrine, and norepinephrine, all remaining as significant predictors in multivariate modeling. Our data confirm that salt-sensitivity of blood pressure is associated with insulin resistance, suggest that salt restriction may be beneficial in SS but perhaps detrimental in SR subjects, and uncover possible differences in mechanisms of insulin resistance between SS and SR, with implications for pharmacological therapy.