ArticleThe Journal of clinical endocrinology and metabolism2011
Opioid receptor blockade improves hypoglycemia-associated autonomic failure in type 1 diabetes mellitus.
Article in The Journal of clinical endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 45 citations in OpenAlex.
- Intranasal Naloxone During Recurrent Exercise in Individuals with Type-1 Diabetes Mellitus: Evaluation of the Clinical Predictors of Pharmacokinetics and Exposure-Response.Journal of clinical pharmacology · 2025Trial
- Effects of Intranasal Naloxone on Hypoglycemia-associated Autonomic Failure in Susceptible Individuals.The Journal of clinical endocrinology and metabolism · 2025Trial
- Effect of short-term use of dapagliflozin on impaired awareness of hypoglycaemia in people with type 1 diabetes.Diabetes, obesity & metabolism · 2021Trial
- Trial
- Evaluation of the counter-regulatory responses to hypoglycaemia in patients with type 1 diabetes during opiate receptor blockade with naltrexone.Diabetes, obesity & metabolism · 2017Trial
- Acute Effects of Oral Dehydroepiandrosterone on Counterregulatory Responses During Repeated Hypoglycemia in Healthy Humans.Diabetes · 2016Trial
- Naltrexone for treatment of impaired awareness of hypoglycemia in type 1 diabetes: A randomized clinical trial.Journal of diabetes and its complicationsTrial
- Spatial correspondence between altered brain function and normative neurotransmitter density maps in Type 1 diabetes mellitus.Journal of endocrinological investigation · 2026Article
- Role of the Adrenal Medulla in Hypoglycaemia-Associated Autonomic Failure-A Diabetic Perspective.Metabolites · 2024Review
- Experimental pharmacological approaches to reverse impaired awareness of hypoglycemia-a review.Frontiers in pharmacology · 2024Review
- Current and future therapies to treat impaired awareness of hypoglycemia.Frontiers in pharmacology · 2023Review
- Experimentally Induced Hypoglycemia-associated Autonomic Failure in Humans: Determinants, Designs, and Drawbacks.Journal of the Endocrine Society · 2022Review
- Heterogeneity in Epinephrine Response to Experimental Hypoglycemia in Type 1 Diabetes and Controls.Journal of the Endocrine Society · 2022Article
- Activation of nucleus accumbens μ-opioid receptors enhances the response to a glycaemic challenge.Journal of neuroendocrinology · 2021Article
- Validation of the Korean version of the Boston Autonomic Symptom Questionnaire.Journal of clinical neurology (Seoul, Korea) · 2021Article
- Clinical approaches to treat impaired awareness of hypoglycaemia.Therapeutic advances in endocrinology and metabolism · 2021Review
- Hypoglycemia unawareness and autonomic dysfunction in diabetes: Lessons learned and roles of diabetes technologies.Journal of diabetes investigation · 2020Review
- Hypoglycemia-associated autonomic failure, counterregulatory responses, and therapeutic options in type 1 diabetes.Annals of the New York Academy of Sciences · 2019Review
- Repetitive hypoglycemia reduces activation of glucose-responsive neurons in C1 and C3 medullary brain regions to subsequent hypoglycemia.American journal of physiology. Endocrinology and metabolism · 2019Article
- Central Mechanisms of Glucose Sensing and Counterregulation in Defense of Hypoglycemia.Endocrine reviews · 2019Review
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4 authors at 1 institution in 1 country.
Funding
Abstract
contextRecurrent hypoglycemia induces hypoglycemia-associated autonomic failure (HAAF), characterized by deterioration in counterregulatory responses. Endogenous opioids may mediate the development of HAAF, and blockade of opioid receptors with naloxone prevented HAAF in nondiabetic subjects.
objectiveWe hypothesized that opioid receptor blockade with naloxone during antecedent hypoglycemia in patients with type 1 diabetes mellitus (T1DM) would prevent the development of HAAF. DESIGN, SETTING, PARTICIPANTS, AND
interventionsEight subjects with T1DM (three women, aged 34 ± 7.4 yr, hemoglobin A1c 7.3 ± 1.1%) were studied on 2 consecutive days on three separate occasions. Day 1 consisted of: 1) two 90-min hypoglycemic clamps (60 mg/dl, N-); 2) two 90-min hypoglycemic clamps (60 mg/dl) with concomitant naloxone infusion (N+); or 3) two 90-min euglycemic clamps (90 mg/dl) with concomitant naloxone infusion (control). Day 2 consisted of hyperinsulinemic stepped hypoglycemic clamps (90, 80, 70, and 60 mg/dl plasma glucose steps).
main outcome measuresDay 2 hypoglycemia counterregulatory hormonal response and glucose turnover [(3-(3)H)-glucose] as indicators of recovery from hypoglycemia.
resultsAntecedent hypoglycemia in N- group resulted in a markedly decreased epinephrine response and a lower rate of endogenous glucose production (EGP) during subsequent hypoglycemia compared with control (75 ± 17 vs. 187 ± 21 pg/ml, P < 0.05 and 0.8 ± 0.1 vs. 1.4 ± 0.2 mg/kg · min, P < 0.05, respectively). In contrast, in the N+ studies, plasma epinephrine was 164 ± 18 pg/ml and EGP was 1.3 ± 0.2 mg/kg · min during subsequent hypoglycemia, both levels similar to those seen in control studies (P = NS vs. control). Plasma glucagon did not increase with hypoglycemia.
conclusionsBlockade of endogenous opioids with naloxone during antecedent hypoglycemia improves HAAF in patients with T1DM by ameliorating the epinephrine response and restoring EGP.
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