title: Adequately adapted insulin secretion and decreased hepatic insulin extraction cause elevated insulin concentrations in insulin resistant non-diabetic adrenal incidentaloma patients.
abstract: 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.
  
  
  OBJECTIVE
  To retrospectively analyze beta-cell function in non-diabetic AI, compared to healthy controls (CON).
  
  
  METHODS
  AI (n=217, 34%males, 57 ± 1 years, body-mass-index:27.7 ± 0.3 kg/m(2)) and CON [n = 25, 32%males, 56 ± 1 years, 26.7 ± 0.8 kg/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 µg/dL into 3 subgroups: pDexa<1.8 µg/dL, pDexa1.8-5 µg/dL and pDexa>5 µg/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 ± 0.2 mg · kg(-1) · min(-1)), pDexa<1.8 µg/dL (4.9 ± 0.3) and pDexa1.8-5 µg/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 ~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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria ; Metabolic Unit, Institute of Biomedical Engineering, National Research Council (ISIB-CNR), Padua, Italy ; Mariahilf Community Pharmacy, Arnoldstein, Austria ; Medical Direction, Specialized Hospital Complex Agathenhof, Micheldorf, Austria.
authors.forename: Christian-Heinz
authors.initials: CH
authors.lastname: Anderwald
authors.forename: Andrea
authors.initials: A
authors.lastname: Tura
authors.forename: Alois
authors.initials: A
authors.lastname: Gessl
authors.forename: Anton
authors.initials: A
authors.lastname: Luger
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Michael
authors.initials: M
authors.lastname: Krebs
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin