{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:42:03Z","timestamp":1787726523867,"version":"build-2784847793"},"reference-count":48,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["1-08-CR-08"],"award-info":[{"award-number":["1-08-CR-08"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"name":"VA Merit Award","award":["1 I01 CX000167-01"],"award-info":[{"award-number":["1 I01 CX000167-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Patients with nonalcoholic fatty liver disease (NAFLD) are characterized by insulin resistance and hyperinsulinism. However, insulin resistance measurements have not been shown to be good diagnostic tools to predict NAFLD in prior studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to assess a newly validated method to measure intact molecules of insulin by mass spectrometry to predict NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients underwent a 2-hour oral glucose tolerance test (OGTT), a liver magnetic resonance spectroscopy (1H-MRS), and a percutaneous liver biopsy if they had a diagnosis of NAFLD. Mass spectrometry was used to measure intact molecules of insulin and C-peptide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 180 patients were recruited (67% male; 52 \u00b1 11 years of age; body mass index [BMI] 33.2 \u00b1 5.7 kg\/m2; 46% with diabetes and 65% with NAFLD). Intact fasting insulin was higher in patients with NAFLD, irrespective of diabetes status. Patients with NAFLD without diabetes showed ~4-fold increase in insulin secretion during the OGTT compared with all other subgroups (P = 0.008). Fasting intact insulin measurements predicted NAFLD in patients without diabetes (area under the receiver operating characteristic curve [AUC] of 0.90 [0.84-0.96]). This was significantly better than measuring insulin by radioimmunoassay (AUC 0.80 [0.71-0.89]; P = 0.007). Intact fasting insulin was better than other clinical variables (eg, aspartate transaminase, triglycerides, high-density lipoprotein, glucose, HbA1c, and BMI) to predict NAFLD. When combined with alanine transaminase (ALT) (intact insulin \u00d7 ALT), it detected NAFLD with AUC 0.94 (0.89-0.99) and positive and negative predictive values of 93% and 88%, respectively. This newly described approach was significantly better than previously validated noninvasive scores such as NAFLD-LFS (P = 0.009), HSI (P &amp;lt; 0.001), and TyG index (P = 0.039).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients without diabetes, accurate measurement of fasting intact insulin levels by mass spectrometry constitutes an easy and noninvasive strategy to predict presence of NAFLD.<\/jats:p><\/jats:sec>","DOI":"10.1210\/clinem\/dgab417","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T13:34:03Z","timestamp":1625060043000},"page":"e4360-e4371","source":"Crossref","is-referenced-by-count":16,"title":["Intact Fasting Insulin Identifies Nonalcoholic Fatty Liver Disease in Patients Without Diabetes"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5570-4396","authenticated-orcid":false,"given":"Fernando","family":"Bril","sequence":"first","affiliation":[{"name":"Internal Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"},{"name":"Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"McPhaul","sequence":"additional","affiliation":[{"name":"Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92675, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srilaxmi","family":"Kalavalapalli","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Lomonaco","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Barb","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meagan E","family":"Gray","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dov","family":"Shiffman","sequence":"additional","affiliation":[{"name":"Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92675, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles M","family":"Rowland","sequence":"additional","affiliation":[{"name":"Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92675, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Cusi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL 32610, USA"},{"name":"Division of Endocrinology, Diabetes and Metabolism, Malcom Randall, VAMC, Gainesville, FL 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"2021120108534359400_CIT0001","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.2337\/dc20-S004","article-title":"4. 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