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Metabolomics Profiling of Patients With A−β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis
- Source :
- Diabetes
- Publication Year :
- 2021
- Publisher :
- American Diabetes Association, 2021.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 70
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....2758a0d78c43e7f8562a1a2ccfb706d0