Adequately Adapted Insulin Secretion and Decreased Hepatic Insulin Extraction Cause Elevated Insulin Concentrations in Insulin Resistant Non-Diabetic Adrenal Incidentaloma Patients

Background: Insulin-resistance is commonly found in adrenal incidentaloma (AI) patients. However, little is known about beta-cell secretion in AI, because comparisons are difficult, since beta-cell-function varies with altered insulin-sensitivity. Objectives: To retrospectively analyze beta-cell function in non-diabetic AI, compared to healthy controls (CON). Methods: AI (n=217, 34% males, 57 +/- 1years, body-mass-index: 27.7 +/- 0.3kg/m(2)) and CON [n=25, 32% males, 56 +/- 1years, 26.7 +/- 0.8kg/m(2)] with comparable anthropometry (p >= 0.31) underwent oral-glucose-tolerance-tests (OGTTs) with glucose, insulin, and C-peptide measurements. 1mg-dexamethasone-suppression-tests were performed in AI. AI were divided according to post-dexamethasone-suppression-test cortisol-thresholds of 1.8 and 5 mu g/dL into 3subgroups: pDexa<1.8 mu g/dL, pDexa1.8-5 mu g/dL and pDexa>5 mu g/dL. Using mathematical modeling, whole-body insulin-sensitivity [Clamp-like-Index (CLIX)], insulinogenic Index, Disposition Index, Adaptation Index, and hepatic insulin extraction were calculated. Results: CLIX was lower in AI combined (4.9 +/- 0.2mg . kg(-1) . min(-1)), pDexa<1.8 mu g/dL (4.9 +/- 0.3) and pDexa1.8-5 mu g/dL (4.7 +/- 0.3, p<0.04 vs. CON:6.7 +/- 0.4). Insulinogenic and Disposition Indexes were 35%-97% higher in AI and each subgroup (p<0.008 vs. CON), whereas C-peptide-derived Adaptation Index, compensating for insulin-resistance, was comparable between AI, subgroups, and CON. Mathematical estimation of insulin-derived (insulinogenic and Disposition) Indexes from associations to insulin-sensitivity in CON revealed that AI-subgroups had similar to 19%-32% higher insulin-secretion than expectable. These insulin-secretion-index differences negatively (r=-0.45, p<0.001) correlated with hepatic insulin extraction, which was 13-16% lower in AI and subgroups (p<0.003 vs.CON). Conclusions: AI-patients show insulin-resistance, but adequately adapted insulin secretion with higher insulin concentrations during an OGTT, because of decreased hepatic insulin extraction; this finding affects all AI-patients, regardless of dexamethasone-suppression-test outcome.