{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:22:08Z","timestamp":1772119328511,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T00:00:00Z","timestamp":1487289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK 20495"],"award-info":[{"award-number":["DK 20495"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK 45735"],"award-info":[{"award-number":["P30 DK 45735"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 DK07058"],"award-info":[{"award-number":["T32 DK07058"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008664","name":"Juvenile Diabetes Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008664","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2017,5]]},"abstract":"\n Aims<\/jats:title>\n \n Hypoglycaemia is the major limiting factor in achieving optimal glycaemic control in people with type 1 diabetes (\n T1DM<\/jats:styled-content>\n ), especially intensively treated patients with impaired glucose counter\u2010regulation during hypoglycaemia. Naloxone, an opiate receptor blocker, has been reported to enhance the acute counter\u2010regulatory response to hypoglycaemia when administered intravenously in humans. The current study was undertaken to investigate the oral formulation of the long\u2010acting opiate antagonist, naltrexone, and determine if it could have a similar effect, and thus might be useful therapeutically in treatment of\n T1DM<\/jats:styled-content>\n patients with a high risk of hypoglycaemia.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and methods<\/jats:title>\n \n We performed a randomized, placebo\u2010controlled, double\u2010blinded, cross\u2010over study in which 9 intensively treated subjects with\n T1DM<\/jats:styled-content>\n underwent a 2\u2010step euglycaemic\u2010hypoglycaemic\u2010hyperinsulinaemic clamp on 2 separate occasions. At 12 hours and at 1\u2009hour before the clamp study, participants received 100\u2009mg of naltrexone or placebo orally. Counter\u2010regulatory hormonal responses were assessed at baseline and during each step of the hyperinsulinaemic\u2010clamp.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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 (\n \n P<\/jats:italic>\n <\/jats:styled-content>\n \u2009=\u2009.05). However, no statistically significant differences in glucagon, cortisol and growth hormone responses were observed.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n In contrast to the intravenous opiate receptor blocker naloxone, overnight administration of the oral long\u2010acting opiate receptor blocker, naltrexone, at a clinically used dose, had a limited effect on the counter\u2010regulatory response to hypoglycaemia in intensively treated subjects with\n T1DM<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12855","type":"journal-article","created":{"date-parts":[[2016,12,17]],"date-time":"2016-12-17T12:33:13Z","timestamp":1481977993000},"page":"615-621","source":"Crossref","is-referenced-by-count":11,"title":["Evaluation of the counter\u2010regulatory responses to hypoglycaemia in patients with type 1 diabetes during opiate receptor blockade with naltrexone"],"prefix":"10.1111","volume":"19","author":[{"given":"Sarita","family":"Naik","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Endocrinology Yale University School of Medicine New Haven Connecticut"},{"name":"Department of Diabetes and Endocrinology, University College Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Belfort\u2010DeAguiar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Endocrinology Yale University School of Medicine New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne\u2010Sophie","family":"Sejling","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Endocrinology Yale University School of Medicine New Haven Connecticut"},{"name":"Department of Cardiology, Nephrology and Endocrinology Nordsj\u00e6llands Hospital Hiller\u00f8d Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Szepietowska","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Endocrinology Yale University School of Medicine New Haven Connecticut"},{"name":"Heart Research Follow\u2010Up Program University of Rochester Medical Center Rochester New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert S.","family":"Sherwin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Endocrinology Yale University School of Medicine New Haven 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