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Evaluation of the Counter-regulatory Responses to Hypoglycemia in Patients with Type 1 Diabetes during Opiate Receptor Blockade with Naltrexone

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AIMS: Hypoglycemia is the major limiting factor in achieving optimal glycemic control in people with type 1 diabetes (T1DM), especially intensively treated patients with impaired glucose counterregulation during hypoglycemia. Naloxone, an opiate receptor blocker, has been reported to enhance the acute counterregulatory response to hypoglycemia when administered intravenously in humans. The current study was undertaken to investigate if the oral formulation of the long acting opiate antagonist, naltrexone, could have a similar effect, and thus might be useful therapeutically in T1DM patients with a high risk for hypoglycemia.

MATERIALS AND METHODS: We performed a randomized, placebo-controlled, double-blinded, cross-over study in which 9 intensively treated subjects with T1DM underwent a 2-step euglycemic-hypoglycemic-hyperinsulinemic clamp on two separate occasions. Twelve hours and 1 hour before the clamp study the participants received 100 mg of naltrexone or placebo orally. Counterregulatory hormonal responses were assessed at baseline and during each step of the hyperinsulinemic-clamp.

RESULTS: Glucose and insulin levels did not differ significantly between the naltrexone and placebo visits; as well as the glucose infusion rates required to keep glucose levels at target. During hypoglycemia, naltrexone, in comparison to the placebo group, induced an increase in epinephrine levels (P=0.05). However, no statistically significant differences in glucagon, cortisol, and growth hormone responses were observed.

CONCLUSION: In contrast to the intravenous opiate receptor blocker naloxone, overnight administration of the oral long acting opiate receptor blocker, naltrexone, at a clinically used dose, had a limited effect on the counterregulatory response to hypoglycemia in intensively treated subjects with T1DM.

Original languageEnglish
JournalDiabetes, Obesity and Metabolism Online
Volume19
Issue number5
Pages (from-to)615-621
ISSN1463-1326
DOIs
Publication statusPublished - 2017

ID: 49641756