{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:52:21Z","timestamp":1787025141048,"version":"build-2736575974"},"reference-count":49,"publisher":"American Diabetes Association","issue":"8","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:p>When stable and near-normoglycemic, patients with \u201cA\u2212\u03b2+\u201d ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A\u2212\u03b2+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as having type 2 diabetes (T2D). Patients with KPD and patients with T1D had higher counterregulatory hormones and lower insulin-to-glucagon ratio than patients with T2D and control subjects. Compared with patients withT2D and control subjects, patients with KPD and patients with T1D had lower free carnitine and higher long-chain acylcarnitines and acetylcarnitine (C2) but lower palmitoylcarnitine (C16)-to-C2 ratio; a positive relationship between C16 and C2 but negative relationship between carnitine and \u03b2-hydroxybutyrate (BOHB); higher branched-chain amino acids (BCAAs) and their ketoacids but lower ketoisocaproate (KIC)-to-Leu, ketomethylvalerate (KMV)-to-Ile, ketoisovalerate (KIV)-to-Val, isovalerylcarnitine-to-KIC+KMV, propionylcarnitine-to-KIV+KMV, KIC+KMV-to-C2, and KIC-to-BOHB ratios; and lower glutamate and 3-methylhistidine. These data suggest that during DKA, patients with KPD resemble patients with T1D in having impaired BCAA catabolism and accelerated fatty acid flux to ketones\u2014a reversal of their distinctive BCAA metabolic defect when stable. The natural history of A\u2212\u03b2+ KPD is marked by chronic but varying dysregulation of BCAA metabolism.<\/jats:p>","DOI":"10.2337\/db21-0066","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T11:55:11Z","timestamp":1621598111000},"page":"1898-1909","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":20,"title":["Metabolomics Profiling of Patients With A\u2212\u03b2+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis"],"prefix":"10.2337","volume":"70","author":[{"given":"Farook","family":"Jahoor","sequence":"first","affiliation":[{"name":"Children\u2019s Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, and Department of Pediatrics, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean W.","family":"Hsu","sequence":"additional","affiliation":[{"name":"Children\u2019s Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, and Department of Pediatrics, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5434-5424","authenticated-orcid":false,"given":"Paras B.","family":"Mehta","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly R.","family":"Keene","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Baylor College of Medicine, Houston, TX"},{"name":"Ben Taub General Hospital, Harris Health System, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchi","family":"Gaba","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX"},{"name":"Ben Taub General Hospital, Harris Health System, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0447-0638","authenticated-orcid":false,"given":"Surya Narayan","family":"Mulukutla","sequence":"additional","affiliation":[{"name":"Diabetes and Endocrinology Institute, DHR Health, Edinburg, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunice","family":"Caducoy","sequence":"additional","affiliation":[{"name":"Children\u2019s Nutrition Research Center, Agricultural Research Service, U.S. Department of Agriculture, and Department of Pediatrics, Baylor College of Medicine, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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