Amino Acids and CART Distinguish A-β+ Ketosis-Prone Diabetes From Type 1 and Type 2 Diabetes During Hyperglycemic Crises

Authors

• Farook Jahoor
• Jean W Hsu
• Kelly R Keene
• W Frank Peacock
• Xiaofang Huang
• Danielle Guffey
• Jinyoung Byun
• Rasmus Bennet
• Ake Lernmark
• Mustafa Tosur
• Ashok Balasubramanyam

Language

English

Publication Date

9-16-2025

Journal

The Journal of Clinical Endocrinology and Metabolism

DOI

10.1210/clinem/dgaf033

PMID

39820433

PMCID

PMC12448646

PubMedCentral® Posted Date

1-16-2025

PubMedCentral® Full Text Version

Post-print

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.

Methods: At an urban hospital emergency center, adults with KPD, T1D, and T2D during hyperglycemic crises with or without diabetic ketoacidosis (DKA), and healthy controls, underwent comparisons of serum metabolite and hormonal profiles and CART analyses. Group differences in concentrations of amino acids, their metabolites, and relationship to glucose counterregulatory hormones were determined, as well as 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 < .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.

Conclusion: 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.

Keywords

Humans, Diabetes Mellitus, Type 2, Amino Acids, Female, Male, Diabetes Mellitus, Type 1, Adult, Hyperglycemia, Middle Aged, Diabetic Ketoacidosis, Biomarkers, Metabolomics, Diagnosis, Differential, Case-Control Studies, catabolic hormones, insulin, metabolism, GAD65-Ab, hyperglycemic crisis, diabetic ketoacidosis

Published Open-Access

yes

Recommended Citation

Jahoor, Farook; Hsu, Jean W; Keene, Kelly R; et al., "Amino Acids and CART Distinguish A-β+ Ketosis-Prone Diabetes From Type 1 and Type 2 Diabetes During Hyperglycemic Crises" (2025). Children’s Nutrition Research Center Staff Publications. 368.
https://digitalcommons.library.tmc.edu/staff_pub/368