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Amino acids and CART distinguish A-β+ Ketosis-Prone Diabetes from type 1 and type 2 diabetes during hyperglycemic crises

Jahoor, Farook ; Hsu, Jean W ; Keene, Kelly R ; Peacock, W Frank ; Huang, Xiaofang ; Guffey, Danielle ; Byun, Jinyoung ; Bennet, Rasmus LU ; Lernmark, Ake LU orcid and Tosur, Mustafa , et al. (2025) In The Journal of clinical endocrinology and metabolism
Abstract

CONTEXT: When clinically stable, patients with A-β+ Ketosis-Prone Diabetes (KPD) manifest unique markers of amino acid metabolism. Biomarkers differentiating KPD from type 1 (T1D) and type 2 diabetes (T2D) during hyperglycemic crises would accelerate diagnosis and management.

OBJECTIVE: Compare serum metabolomics of KPD, T1D and T2D patients during hyperglycemic crises, and utilize Classification and Regression Tree (CART) modeling to distinguish these forms of diabetes.

SETTING: Urban hospital emergency center.

PARTICIPANTS: Adults with KPD, T1D and T2D during hyperglycemic crises (with or without diabetic ketoacidosis (DKA), and healthy controls.

INTERVENTIONS: Comparisons of serum metabolite and hormonal... (More)

CONTEXT: When clinically stable, patients with A-β+ Ketosis-Prone Diabetes (KPD) manifest unique markers of amino acid metabolism. Biomarkers differentiating KPD from type 1 (T1D) and type 2 diabetes (T2D) during hyperglycemic crises would accelerate diagnosis and management.

OBJECTIVE: Compare serum metabolomics of KPD, T1D and T2D patients during hyperglycemic crises, and utilize Classification and Regression Tree (CART) modeling to distinguish these forms of diabetes.

SETTING: Urban hospital emergency center.

PARTICIPANTS: Adults with KPD, T1D and T2D during hyperglycemic crises (with or without diabetic ketoacidosis (DKA), and healthy controls.

INTERVENTIONS: Comparisons of serum metabolite and hormonal profiles, and CART analysis.

MAIN OUTCOME MEASURES: Group differences in concentrations of amino acids, their metabolites and relationship to glucose counterregulatory hormones; C-peptide cutoffs and analytes to distinguish KPD, T1D and T2D.

RESULTS: Concentrations of most amino acids were similar in KPD and T1D and lower compared to T2D (P<0.05). Glucagon and cortisol concentrations were correlated with 3-methylhistidine and blood urea nitrogen in KPD but not in T1D. A C-peptide cutoff of 0.496 ng/mL differentiated T1D from KPD during DKA. CART revealed that a regression model based on the concentrations of β-hydroxybutyrate, C-peptide, glucagon, alpha-keto-β-methylvalerate, cystine and myristoyl-L-carnitine distinguished KPD from T1D and T2D.

CONCLUSIONS: During DKA, KPD and T1D patients have similarly altered amino acid profiles that differentiate them from T2D patients. Elevated protein catabolic hormones drive altered amino acid metabolism in KPD, rather than insulin deficiency as with T1D. A combination of 6 analytes differentiates KPD from T1D and T2D during hyperglycemic crises.

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epub
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The Journal of clinical endocrinology and metabolism
publisher
Oxford University Press
external identifiers
  • pmid:39820433
ISSN
1945-7197
DOI
10.1210/clinem/dgaf033
language
English
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yes
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© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.
id
632c018a-7ba2-49bc-8f55-e7b84c9fd5ca
date added to LUP
2025-01-25 19:10:53
date last changed
2025-04-04 14:50:42
@article{632c018a-7ba2-49bc-8f55-e7b84c9fd5ca,
  abstract     = {{<p>CONTEXT: When clinically stable, patients with A-β+ Ketosis-Prone Diabetes (KPD) manifest unique markers of amino acid metabolism. Biomarkers differentiating KPD from type 1 (T1D) and type 2 diabetes (T2D) during hyperglycemic crises would accelerate diagnosis and management.</p><p>OBJECTIVE: Compare serum metabolomics of KPD, T1D and T2D patients during hyperglycemic crises, and utilize Classification and Regression Tree (CART) modeling to distinguish these forms of diabetes.</p><p>SETTING: Urban hospital emergency center.</p><p>PARTICIPANTS: Adults with KPD, T1D and T2D during hyperglycemic crises (with or without diabetic ketoacidosis (DKA), and healthy controls.</p><p>INTERVENTIONS: Comparisons of serum metabolite and hormonal profiles, and CART analysis.</p><p>MAIN OUTCOME MEASURES: Group differences in concentrations of amino acids, their metabolites and relationship to glucose counterregulatory hormones; C-peptide cutoffs and analytes to distinguish KPD, T1D and T2D.</p><p>RESULTS: Concentrations of most amino acids were similar in KPD and T1D and lower compared to T2D (P&lt;0.05). Glucagon and cortisol concentrations were correlated with 3-methylhistidine and blood urea nitrogen in KPD but not in T1D. A C-peptide cutoff of 0.496 ng/mL differentiated T1D from KPD during DKA. CART revealed that a regression model based on the concentrations of β-hydroxybutyrate, C-peptide, glucagon, alpha-keto-β-methylvalerate, cystine and myristoyl-L-carnitine distinguished KPD from T1D and T2D.</p><p>CONCLUSIONS: During DKA, KPD and T1D patients have similarly altered amino acid profiles that differentiate them from T2D patients. Elevated protein catabolic hormones drive altered amino acid metabolism in KPD, rather than insulin deficiency as with T1D. A combination of 6 analytes differentiates KPD from T1D and T2D during hyperglycemic crises.</p>}},
  author       = {{Jahoor, Farook and Hsu, Jean W and Keene, Kelly R and Peacock, W Frank and Huang, Xiaofang and Guffey, Danielle and Byun, Jinyoung and Bennet, Rasmus and Lernmark, Ake and Tosur, Mustafa and Balasubramanyam, Ashok}},
  issn         = {{1945-7197}},
  language     = {{eng}},
  month        = {{01}},
  publisher    = {{Oxford University Press}},
  series       = {{The Journal of clinical endocrinology and metabolism}},
  title        = {{Amino acids and CART distinguish A-β+ Ketosis-Prone Diabetes from type 1 and type 2 diabetes during hyperglycemic crises}},
  url          = {{http://dx.doi.org/10.1210/clinem/dgaf033}},
  doi          = {{10.1210/clinem/dgaf033}},
  year         = {{2025}},
}