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Noncardioselective \u03b2\u2010blockers not only reduce portal hypertension and prevent variceal bleeding in cirrhosis but also impair glucose tolerance and insulin sensitivity in other settings. This study aimed to determine whether nonselective \u03b2\u2010blockade with nadolol impairs glucose metabolism in liver cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomized, double\u2010blind, placebo\u2010controlled crossover trial of nadolol in cirrhotic patients examined insulin sensitivity, disposition index, and glucose tolerance. Stable cirrhotic patients of mixed etiology underwent an intravenous glucose tolerance test and hyperinsulinemic\u2010euglycemic clamp for the measurement of insulin secretion and insulin sensitivity (n\u00a0=\u00a016) and a 75\u2010g oral glucose tolerance test (n\u00a0=\u00a017). These measurements were conducted twice (after 3\u00a0months of treatment with nadolol or placebo and, after a 1\u2010month washout period, after 3\u00a0months on the alternative treatment). Total body fat and plasma catecholamines were measured at the end of each 3\u2010month treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with placebo, nadolol treatment reduced insulin sensitivity (79.7\u00a0\u00b1\u00a010.1 vs 99.6\u00a0\u00b1\u00a010.3\u00a0\u03bcL\/kg fat\u2010free mass\u00b7min<jats:sup>\u22121<\/jats:sup>\u00b7(mU\/L)<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.005). Insulin secretion was unchanged (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.24), yielding a lower disposition index with nadolol (6083\u00a0\u00b1\u00a02007 vs 8692\u00a0\u00b1\u00a02036, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.050). There was no change in total body fat or plasma catecholamines. A 2\u2010hour plasma glucose concentration from the oral glucose tolerance test was higher on nadolol than placebo (10.8\u00a0\u00b1\u00a00.9 vs 9.9\u00a0\u00b1\u00a00.9\u00a0mmol\/L, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.035).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Nadolol significantly worsened insulin sensitivity, glycemia, and disposition index in patients with liver cirrhosis. These findings may have significant clinical implications because cirrhosis is already associated with an increased prevalence of diabetes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dmrr.2859","type":"journal-article","created":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T05:22:37Z","timestamp":1474867357000},"source":"Crossref","is-referenced-by-count":5,"title":["Nadolol reduces insulin sensitivity in liver cirrhosis: a randomized double\u2010blind crossover trial"],"prefix":"10.1002","volume":"33","author":[{"given":"Wai Gin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Surgery University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rinki","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John 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