Metabolomics Profiling of Patients With A-β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis
(2021) In Diabetes 70(8). p.1898-1909- 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... (More)
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.
(Less)
- author
- 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
LU
; Lernmark, Ake
LU
and Balasubramanyam, Ashok
(Less) - organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 70
- issue
- 8
- pages
- 1898 - 1909
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- pmid:34021044
- scopus:85114707703
- ISSN
- 1939-327X
- DOI
- 10.2337/db21-0066
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2021 by the American Diabetes Association. Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
- id
- d9c2ebba-799f-4cc6-b77a-9cec903a0a1f
- date added to LUP
- 2021-09-20 12:16:50
- date last changed
- 2024-05-18 14:53:44
@article{d9c2ebba-799f-4cc6-b77a-9cec903a0a1f,
abstract = {{<p>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.</p>}},
author = {{Jahoor, Farook and Hsu, Jean W. and Mehta, Paras B. and Keene, Kelly R. and Gaba, Ruchi and Mulukutla, Surya Narayan and Caducoy, Eunice and Peacock, W. Frank and Patel, Sanjeet G. and Bennet, Rasmus and Lernmark, Ake and Balasubramanyam, Ashok}},
issn = {{1939-327X}},
language = {{eng}},
number = {{8}},
pages = {{1898--1909}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{Metabolomics Profiling of Patients With A-β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis}},
url = {{http://dx.doi.org/10.2337/db21-0066}},
doi = {{10.2337/db21-0066}},
volume = {{70}},
year = {{2021}},
}