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 funct...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3797754?pdf=render |
| _version_ | 1818251810825043968 |
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| author | Christian-Heinz Anderwald Andrea Tura Alois Gessl Anton Luger Giovanni Pacini Michael Krebs |
| author_facet | Christian-Heinz Anderwald Andrea Tura Alois Gessl Anton Luger Giovanni Pacini Michael Krebs |
| author_sort | Christian-Heinz Anderwald |
| collection | DOAJ |
| description | 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 ± 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. |
| first_indexed | 2024-12-12T16:14:12Z |
| format | Article |
| id | doaj.art-578623172b0e4421b2d97346e2fe77d4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T16:14:12Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-578623172b0e4421b2d97346e2fe77d42022-12-22T00:19:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7732610.1371/journal.pone.0077326Adequately adapted insulin secretion and decreased hepatic insulin extraction cause elevated insulin concentrations in insulin resistant non-diabetic adrenal incidentaloma patients.Christian-Heinz AnderwaldAndrea TuraAlois GesslAnton LugerGiovanni PaciniMichael KrebsBACKGROUND: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 ± 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.http://europepmc.org/articles/PMC3797754?pdf=render |
| spellingShingle | Christian-Heinz Anderwald Andrea Tura Alois Gessl Anton Luger Giovanni Pacini Michael Krebs Adequately adapted insulin secretion and decreased hepatic insulin extraction cause elevated insulin concentrations in insulin resistant non-diabetic adrenal incidentaloma patients. PLoS ONE |
| title | Adequately adapted insulin secretion and decreased hepatic insulin extraction cause elevated insulin concentrations in insulin resistant non-diabetic adrenal incidentaloma patients. |
| title_full | Adequately adapted insulin secretion and decreased hepatic insulin extraction cause elevated insulin concentrations in insulin resistant non-diabetic adrenal incidentaloma patients. |
| title_fullStr | Adequately adapted insulin secretion and decreased hepatic insulin extraction cause elevated insulin concentrations in insulin resistant non-diabetic adrenal incidentaloma patients. |
| title_full_unstemmed | Adequately adapted insulin secretion and decreased hepatic insulin extraction cause elevated insulin concentrations in insulin resistant non-diabetic adrenal incidentaloma patients. |
| title_short | Adequately adapted insulin secretion and decreased hepatic insulin extraction cause elevated insulin concentrations in insulin resistant non-diabetic adrenal incidentaloma patients. |
| title_sort | adequately adapted insulin secretion and decreased hepatic insulin extraction cause elevated insulin concentrations in insulin resistant non diabetic adrenal incidentaloma patients |
| url | http://europepmc.org/articles/PMC3797754?pdf=render |
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