Journal of the Endocrine Society | VOL. 6

Experimentally Induced Hypoglycemia-associated Autonomic Failure in Humans: Determinants, Designs, and Drawbacks.

Publication Date Oct 1, 2022


Iatrogenic hypoglycemia remains one of the leading hindrances of optimal glycemic management in insulin-treated diabetes. Recurring hypoglycemia leads to a condition of hypoglycemia-associated autonomic failure (HAAF). HAAF refers to a combination of (i) impaired hormonal counterregulatory responses and (ii) hypoglycemia unawareness to subsequent hypoglycemia, substantially increasing the risk of severe hypoglycemia. Several studies since the 1990s have experimentally induced HAAF, yielding variable results. The aim of this review was to assess the varying designs, clinical outcomes, potential assets, and drawbacks related to these studies. A systemic literature search was conducted on PubMed and Embase in winter 2021 to include all human studies attempting to experimentally induce HAAF. In different combinations, the search terms used were "hypoglycemia-associated autonomic failure," "HAAF," "hypoglycemia," "recurring," "recurrent," "repeated," "consecutive," and "unawareness," yielding 1565 publications. Inclusion criteria were studies that had aimed at experimentally inducing HAAF and measuring outcomes of hormonal counterregulation and awareness of hypoglycemia. The literature search yielded 27 eligible publications, of which 20 were successful in inducing HAAF while statistical significantly impairing both hormonal counterregulation and impairing awareness of hypoglycemia to subsequent hypoglycemia. Several factors were of significance as regards inducing HAAF: Foremost, the duration of antecedent hypoglycemia should be...


Hypoglycemia-associated Autonomic Failure Awareness Of Hypoglycemia Insulin-treated Diabetes Potential Assets Hormonal Counterregulation Counterregulation Of Hypoglycemia Insulin Dosage Duration Of Hypoglycemia Search Terms Qualified Studies

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No potential conflict of interest was reported by the authors. The conception and design of the study, acquisition of data, analysis and interpretatio...

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