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Diabetes Obes Metab. 2017 May;19(5):615-621. doi: 10.1111/dom.12855. Epub 2017 Feb 17.

Evaluation of the counter-regulatory responses to hypoglycaemia in patients with type 1 diabetes during opiate receptor blockade with naltrexone.

Author information

1
Department of Internal Medicine and Endocrinology, Yale University School of Medicine, New Haven, Connecticut.
2
Department of Diabetes and Endocrinology, University College Hospital, London, UK.
3
Department of Cardiology, Nephrology and Endocrinology, Nordsjaellands Hospital, Hillerød, Denmark.
4
Heart Research Follow-Up Program, University of Rochester Medical Center, Rochester, New York.

Abstract

AIMS:

Hypoglycaemia is the major limiting factor in achieving optimal glycaemic control in people with type 1 diabetes (T1DM), especially intensively treated patients with impaired glucose counter-regulation during hypoglycaemia. Naloxone, an opiate receptor blocker, has been reported to enhance the acute counter-regulatory response to hypoglycaemia when administered intravenously in humans. The current study was undertaken to investigate the oral formulation of the long-acting opiate antagonist, naltrexone, and determine if it could have a similar effect, and thus might be useful therapeutically in treatment of T1DM patients with a high risk of hypoglycaemia.

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 euglycaemic-hypoglycaemic-hyperinsulinaemic clamp on 2 separate occasions. At 12 hours and at 1 hour before the clamp study, participants received 100 mg of naltrexone or placebo orally. Counter-regulatory hormonal responses were assessed at baseline and during each step of the hyperinsulinaemic-clamp.

RESULTS:

Glucose and insulin levels did not differ significantly between the naltrexone and placebo visits; nor did the glucose infusion rates required to keep glucose levels at target. During hypoglycaemia, naltrexone, in comparison with the placebo group, induced an increase in epinephrine levels ( P  = .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 counter-regulatory response to hypoglycaemia in intensively treated subjects with T1DM.

KEYWORDS:

counter-regulatory hormonal response; hypoglycaemia; naltrexone

PMID:
27987236
PMCID:
PMC6015737
DOI:
10.1111/dom.12855
[Indexed for MEDLINE]
Free PMC Article

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