Abstract 500: Differential Predictors of Insulin Resistance in Non-Diabetic, Salt-Resistant and Salt-Sensitive Subjects
Normotensive (NT=16) and untreated hypertensive (HT=23) subjects, without diabetes, underwent an inpatient study of salt-sensitivity of blood pressure (24 hr salt loading [HI] with 2L saline and 160 mMol Na diet, and 24 hr salt depletion [LO] with 10 mMol Na diet and furosemide 40 mg x3); and of insulin sensitivity (homeostatic index, SIHOMA). A fall of ≥10 mmHg in average systolic BP (noon to 10 pm) from HI to LO, was the cutoff for defining salt-sensitive (SS) vs salt-resistant (SR) subjects. Laboratory data were obtained before HI, and after HI and LO. NT were younger (40±2 vs 46±2 years, p<0.05) and had lower aldosterone (Aldo; 10±1 vs 22±2 ng/dl, p<0.01) than HT. Despite similar BMIs (30±2 vs 34±1 Kg/m2), plasma insulin was lower (10±1 vs 28±3 μU/ml, p<0.01) and SIHOMA higher (0.61±0.09 vs 0.18±0.02 ml*L/[μU*mmol], p<0.01) in NT than HT. SS prevalence was 37% in NT and 43% in HT. BP fall was not different between NT and HT, within the SS (-13±2 vs -16±2 mmHg) or SR (-1±1 vs -3±1) groups. Differences between SS and SR included greater percentage of Blacks (63 vs 26%), lower PRA (1.0±0.3 vs 1.9±0.4 ngAI/ml/hr), higher Aldo-renin ratio (32±6 vs 17±3 ng*dl-1/ngAI*ml-1*hr-1) and lower SIHOMA (0.25±0.03 vs 0.43±0.09) in SS (p<0.05 for all). HI suppressed PRA and Aldo, whereas LO stimulated PRA, Aldo and catecholamines (CAT) in both SR and SS. SIHOMA of SR was diminished by LO to the level of SS. Univariate correlates of SIHOMA in SR were: age (r=-0.31, p<0.02), MAP (r=-0.48, p<0.001), BMI (r=-0.54, p<0.001), triglycerides (r=-0.43, p<0.001), and Aldo (r=-0.42, p<0.001). Those in SS were: age (r=-0.31, p<0.05), MAP (r=-0.38, p<0.01) and CAT (r=-0.32, p<0.03). Multivariate regressions showed that independent predictors of SIHOMA in SR were BMI and Aldo (SIHOMA=1.35 - 0.025BMI - 0.013Aldo, r2=0.50, F=33.5, p<0.0001); whereas those in SS were MAP and CAT (SIHOMA=0.80 - 0.0055MAP - 0.0003CAT, r2=0.31, F=10.1, p<0.0003). We conclude: 1. SS are more insulin resistant; 2. acute salt-depletion worsens insulin sensitivity of SR; and most importantly, 3. the hormonal predictors of insulin resistance are different in SR vs SS. Our data suggest that insulin sensitivity could be improved by mineralocorticoid blockers in SR, whereas adrenergic antagonists may be more effective in SS.
- © 2012 by American Heart Association, Inc.