Potential approaches to prevent hypoglycemia-associated autonomic failure

Eric Lontchi-Yimagou, Jee Young You, Michelle Carey, Ilan Gabriely, Harry Shamoon, Meredith Hawkins

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations


Clear health benefits are associated with intensive glucose control in type 1 diabetes mellitus (T1DM). However, maintaining near-normal glycemia remains an elusive goal for many patients, in large part owing to the risk of severe hypoglycemia. In fact, recurrent episodes of hypoglycemia lead to hypoglycemia-associated autonomic failure' (HAAF), characterized by defective counter-regulatory responses to hypoglycemia. Extensive studies to understand the mechanisms underlying HAAF have revealed multiple potential etiologies, suggesting various approaches to prevent the development of HAAF. In this review, we present an overview of the literature focused on pharmacological approaches that may prevent the development of HAAF. The purported underlying mechanisms of HAAF include: 1) central mechanisms (opioid receptors, ATP-sensitive K+(K ATP) channels, adrenergic receptors, serotonin selective receptor inhibitors, Î 3-aminobuyric acid receptors, N-methyl D-aspartate receptors); 2) hormones (cortisol, estrogen, dehydroepiandrosterone (DHEA) or DHEA sulfate, glucagon-like peptide-1) and 3) nutrients (fructose, free fatty acids, ketones), all of which have been studied vis-à-vis their ability to impact the development of HAAF. A careful review of the current literature reveals many promising therapeutic approaches to treat or reduce this important limitation to optimal glycemic control.

Original languageEnglish (US)
Pages (from-to)641-647
Number of pages7
JournalJournal of Investigative Medicine
Issue number3
StatePublished - Mar 2018


  • diabetes complications
  • diabetes mellitus
  • disease management
  • hypoglycemia

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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