Metabolomics Profiling of Patients With A-β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis.
In: Diabetes, Jg. 70 (2021-08-01), Heft 8, S. 1898-1909
academicJournal
Zugriff:
When stable and near-normoglycemic, patients with "A-β+" 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-β+ 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 β-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-a reversal of their distinctive BCAA metabolic defect when stable. The natural history of A-β+ KPD is marked by chronic but varying dysregulation of BCAA metabolism. [ABSTRACT FROM AUTHOR]
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Metabolomics Profiling of Patients With A-β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis.
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Autor/in / Beteiligte Person: | Jahoor, Farook ; Hsu, Jean W. ; Mehta, Paras B. ; Keene, Kelly R. ; Gaba, Ruchi ; Mulukutla, Surya Narayan ; Caducoy, Eunice ; Peacock, W. Frank ; Patel, Sanjeet G. ; Bennet, Rasmus ; Lernmark, Ake ; Balasubramanyam, Ashok ; Rasmus, Bennet ; Ake, Lernmark |
Zeitschrift: | Diabetes, Jg. 70 (2021-08-01), Heft 8, S. 1898-1909 |
Veröffentlichung: | 2021 |
Medientyp: | academicJournal |
ISSN: | 0012-1797 (print) |
DOI: | 10.2337/db21-0066 |
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