Decreased branched-chain amino acids and elevated fatty acids during antecedent hypoglycemia in type 1 diabetes

Rui She, Naba Hassan Al-Sari, Ismo Matias Mattila, Anne Sophie Sejling, Jens Pedersen, Cristina Legido-Quigley, Ulrik Pedersen-Bjergaard*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

2 Citations (Scopus)
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Abstract

Introduction Hypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to hypoglycemia. Limited data on metabolic adaptation to recurrent hypoglycemia are available. This study examined the acute metabolic responses to hypoglycemia and the effect of antecedent hypoglycemia on these responses in type 1 diabetes. Research design and methods Twenty-one outpatients with type 1 diabetes with normal or impaired awareness of hypoglycemia participated in a study assessing the response to hypoglycemia on 2 consecutive days by a hyperinsulinemic glucose clamp. Participants underwent a period of normoglycemia and a period of hypoglycemia during the hyperinsulinemic glucose clamp. Plasma samples were taken during normoglycemia and at the beginning and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry. Results In total, 68 metabolites were studied. On day 1, concentrations of the branched-chain amino acids, leucine (p=3.8×10 -3) and isoleucine (p=2.2×10 -3), decreased during hypoglycemia. On day 2, during hypoglycemia, five amino acids (including leucine and isoleucine) significantly decreased, and two fatty acids (tetradecanoic and oleic acids) significantly increased (p<0.05). Although more metabolites responded to hypoglycemia on day 2, the responses of the single metabolites were not statistically significant between the 2 days. Conclusions In individuals with type 1 diabetes, one episode of hypoglycemia decreases leucine and isoleucine concentrations. Antecedent hypoglycemia results in the decrement of five amino acids and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptation. However, more studies are needed to gain a comprehensive understanding of the consequences of these alterations. Trial registration number NCT01337362.

Original languageEnglish
Article number003327
JournalBMJ Open Diabetes Research and Care
Volume11
Issue number3
Number of pages8
ISSN2052-4897
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords

  • Diabetes complication
  • Energy metabolism
  • Hypoglycemia
  • Type 1 diabetes mellitus

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