Aminoaciduria and metabolic dysregulation during diabetic ketoacidosis: Results from the diabetic kidney alarm (DKA) study

J Diabetes Complications. 2022 Jun;36(6):108203. doi: 10.1016/j.jdiacomp.2022.108203. Epub 2022 Apr 28.

Abstract

Objective: We examined changes in the excretion of various amino acids and in glycolysis and ketogenesis-related metabolites, during and after diabetic ketoacidosis (DKA) diagnosis, in youth with known or new onset type 1 diabetes (T1D).

Methods: Urine samples were collected from 40 youth with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.1, blood glucose 451 ± 163 mg/dL) at 3 time points: 0-8 h and 12-24 h after starting an insulin infusion, and 3 months after hospital discharge. Mixed-effects models evaluated the changes in amino acids and other metabolites in the urine.

Results: Concentrations of urine histidine, threonine, tryptophan, and leucine per creatinine were highest at 0-8 h (148.8 ± 23.5, 59.5 ± 12.3, 15.4 ± 1.4, and 24.5 ± 2.4% of urine creatinine, respectively), and significantly decreased over 3 months (p = 0.028, p = 0.027, p = 0.019, and p < 0.0001, respectively). Urine histidine, threonine, tryptophan, and leucine per urine creatinine decreased by 10.6 ± 19.2, 0.7 ± 0.9, 1.3 ± 0.9, and 0.5 ± 0.3-fold, respectively, between 0 and 8 h and 3 months.

Conclusions: In our study, DKA was associated with profound aminoaciduria, suggestive of proximal tubular dysfunction analogous to Fanconi syndrome.

Keywords: Aminoaciduria; Diabetic ketoacidosis; Diabetic nephropathy; Pediatrics; Type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acids
  • Child
  • Creatinine
  • Diabetes Mellitus, Type 1* / diagnosis
  • Diabetic Ketoacidosis* / complications
  • Diabetic Nephropathies* / complications
  • Diabetic Nephropathies* / etiology
  • Female
  • Histidine
  • Humans
  • Leucine
  • Male
  • Threonine
  • Tryptophan

Substances

  • Amino Acids
  • Threonine
  • Histidine
  • Tryptophan
  • Creatinine
  • Leucine