Soluble Receptor for Glycation End-products Concentration Increases Following the Treatment of Severe Diabetic Ketoacidosis

J Clin Res Pediatr Endocrinol. 2020 Jun 3;12(2):160-167. doi: 10.4274/jcrpe.galenos.2019.2019.0076. Epub 2019 Sep 13.

Abstract

Objective: To determine the time relationships of soluble receptor for glycation end-products (sRAGE), [a decoy of the advanced glycation end-products (AGE)-RAGE axis] and D-lactate, (a metabolite of methylglyoxal) in the inflammatory response to diabetic ketoacidosis (DKA).

Methods: Sixteen children and adolescents with type 1 diabetes (T1D) had blood samples obtained, 6-12 hours into treatment, at three weeks and three months post start of treatment. sRAGE and D-lactate concentrations at three months were considered baseline. Expression of RAGE was investigated in the myocardium of a newly diagnosed and untreated young person with fatal T1D/DKA.

Results: sRAGE 6-12 hours after the start of treatment was 39% lower than the values at two weeks (p=0.0036) and at three months (p=0.0023) post treatment. D-lactate was higher during treatment than at three weeks (p=0.04) and at three months (p=0.035).

Conclusion: sRAGE concentration was decreased during treatment, compared to concentrations at two weeks and three months after treatment. The increased D-lactate during treatment was in keeping with the known increase in dicarbonyls at this time. The finding of RAGE expression in a young myocardium prior to DKA treatment suggested cardiovascular inflammation pre-treatment and at a young age.

Keywords: Diabetic ketoacidosis; D-lactate; myocarditis; soluble receptor for advanced glycation end-products.

MeSH terms

  • Adolescent
  • Child
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetic Ketoacidosis / blood*
  • Diabetic Ketoacidosis / drug therapy*
  • Diabetic Ketoacidosis / etiology
  • Female
  • Glycation End Products, Advanced / blood*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology*
  • Inflammation / blood*
  • Insulin / administration & dosage
  • Lactic Acid / blood*
  • Longitudinal Studies
  • Male
  • Myocarditis / blood
  • Receptor for Advanced Glycation End Products / blood*
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • AGER protein, human
  • Glycation End Products, Advanced
  • Hypoglycemic Agents
  • Insulin
  • Receptor for Advanced Glycation End Products
  • Lactic Acid