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Experimental Pharmacological Approaches to Reverse Impaired Awareness of Hypoglycemia-a Review

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Journal Front Pharmacol
Date 2024 Feb 7
PMID 38323079
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Abstract

The colossal global burden of diabetes management is compounded by the serious complication of hypoglycemia. Protective physiologic hormonal and neurogenic counterregulatory responses to hypoglycemia are essential to preserve glucose homeostasis and avert serious morbidity. With recurrent exposure to hypoglycemic episodes over time, these counterregulatory responses to hypoglycemia can diminish, resulting in an impaired awareness of hypoglycemia (IAH). IAH is characterized by sudden neuroglycopenia rather than preceding cautionary autonomic symptoms. IAH increases the risk of subsequent sudden and severe hypoglycemic episodes in patients with diabetes. The postulated causative mechanisms behind IAH are complex and varied. It is therefore challenging to identify a single effective therapeutic strategy. In this review, we closely examine the efficacy and feasibility of a myriad of pharmaceutical interventions in preventing and treating IAH as described in clinical and preclinical studies. Pharmaceutical agents outlined include N-acetyl cysteine, GABA A receptor blockers, opioid receptor antagonists, AMP activated protein kinase agonists, potassium channel openers, dehydroepiandrosterone, metoclopramide, antiadrenergic agents, antidiabetic agents and glucagon.

References
1.
Zhu W, Czyzyk D, Paranjape S, Zhou L, Horblitt A, Szabo G . Glucose prevents the fall in ventromedial hypothalamic GABA that is required for full activation of glucose counterregulatory responses during hypoglycemia. Am J Physiol Endocrinol Metab. 2010; 298(5):E971-7. PMC: 2867375. DOI: 10.1152/ajpendo.00749.2009. View

2.
Palani G, Stortz E, Moheet A . Clinical Presentation and Diagnostic Approach to Hypoglycemia in Adults Without Diabetes Mellitus. Endocr Pract. 2022; 29(4):286-294. DOI: 10.1016/j.eprac.2022.11.010. View

3.
Roederer M, Ela S, Staal F, Herzenberg L . N-acetylcysteine: a new approach to anti-HIV therapy. AIDS Res Hum Retroviruses. 1992; 8(2):209-17. DOI: 10.1089/aid.1992.8.209. View

4.
McCrimmon R, Fan X, Cheng H, McNay E, Chan O, Shaw M . Activation of AMP-activated protein kinase within the ventromedial hypothalamus amplifies counterregulatory hormone responses in rats with defective counterregulation. Diabetes. 2006; 55(6):1755-60. DOI: 10.2337/db05-1359. View

5.
Cruz A, Partridge K, Malekizadeh Y, Vlachaki Walker J, Potter P, Pye K . Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats. Front Endocrinol (Lausanne). 2022; 12:697445. PMC: 8718766. DOI: 10.3389/fendo.2021.697445. View