Metabolomics Profiling of Patients With A−β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis
| العنوان: | Metabolomics Profiling of Patients With A−β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis |
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| المؤلفون: | Kelly Rogers Keene, Farook Jahoor, Ruchi Gaba, Sanjeet Patel, Surya N. Mulukutla, Rasmus Bennet, Eunice I. Caducoy, Paras B. Mehta, Ashok Balasubramanyam, Åke Lernmark, W. Frank Peacock, Jean W. Hsu |
| المصدر: | Diabetes |
| بيانات النشر: | American Diabetes Association, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, endocrine system diseases, Diabetic ketoacidosis, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Diabetic Ketoacidosis, chemistry.chemical_compound, Carnitine, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Metabolomics, Acetylcarnitine, Palmitoylcarnitine, Autoantibodies, Type 1 diabetes, business.industry, nutritional and metabolic diseases, Genetics/Genomes/Proteomics/Metabolomics, Middle Aged, medicine.disease, Diabetes Mellitus, Type 1, Endocrinology, Diabetes Mellitus, Type 2, chemistry, Metabolome, Female, business, Amino Acids, Branched-Chain, Ketosis-prone diabetes, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1939-327X 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2758a0d78c43e7f8562a1a2ccfb706d0Test https://doi.org/10.2337/db21-0066Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2758a0d78c43e7f8562a1a2ccfb706d0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1939327X 00121797 |
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