OR31-6 Insulin Sensitivity and Pancreatic Beta-Cell Function in Patients with Primary Aldosteronism

Abstract

Insulin sensitivity and pancreatic beta-cell function are primary determinants of glucose tolerance. Primary aldosteronism (PA) is associated with increased risk for glucose intolerance. However, its effects on insulin sensitivity and β-cell function have shown mixed results. In this study, we compared indices of insulin sensitivity and pancreatic β-cell function derived from an oral glucose tolerance test (OGTT) in patients from two cohorts: subjects with PA (n=25) and essential hypertension control (EHC) subjects. The EHC controls (n=25) were similar in age and BMI range, gender composition (female, n=14), and number of subjects with type 2 diabetes (n=3). Group comparisons were performed after adjusting for age, sex, and BMI; data is presented as unadjusted mean ± SD. As expected, the PA group show lower potassium concentrations compared to the EHC group, as well as elevated aldosterone and reduced renin levels. Mean arterial pressure was not significantly different between the groups (PA:100.6 ± 11.7, EHC: 96.7 ± 15.5 mm Hg, p=0.22). The area under the curve (AUC) for insulin during an OGTT, but not glucose, was higher in the PA group (insulin AUC: 14831 ± 9545 vs. 8582 ± 4948, μU/mL∙min, p<0.05). Whole-body and hepatic insulin sensitivity were determined using surrogate indices and oral minimal model (SIMM) analysis. PA individuals were found to be less insulin sensitive compared to EHC subjects (Quantitative insulin sensitivity check index (QUICKI): 0.337 ± 0.035 vs. 0.367 ± 0.062, p<0.001; Matsuda Index: 3.98 ± 2.33 vs. 7.24 ± 6.50, p<0.001; and SIMM: 1.01x10-3 ± 2.01x10-3 vs. 1.87x10-3 ± 2.71x10-3, min-1 per μU/mL, p=0.08). The hepatic insulin resistance index (HIRI) was significantly higher in PA individuals (HIRI: 5.62 ± 4.52 vs. 4.02 ± 2.78, mg/dL∙ μU/mL ∙ 106, p<0.001), suggesting decreased hepatic insulin sensitivity. Insulinogenic index (IGI), a measure of β -cell function is calculated as change in insulin concentrations divided by change in glucose from 0 to 30 min (ΔI0-30/ΔG0-30). IGI was slightly higher in the PA cohort (169 ± 150 vs. 124 ± 122, pmol/mmol, p=0.06). Oral disposition index (DI), a marker of integrated islet β-cell function, is the product of insulin secretion and sensitivity derived from OGTT. DI was similar between the groups (561 ± 434 vs. 605 ± 517, p=0.80). This accounts for the similar glucose tolerance between the groups. In summary, insulin sensitivity is significantly lower in PA and is accompanied by a compensatory increase in β-cell function. These results suggest that excess aldosterone and/or other steroids in the context of PA may negatively affect insulin action without adversely impacting beta-cell function.