Nadolol reduces insulin sensitivity in liver cirrhosis: a randomized double-blind crossover trial

作者：Lee Wai Gin; Murphy Rinki; McCall John L; Gane Edward J; Soop Mattias; Tura Andrea; Plank Lindsay D^*

来源：DIABETES-METABOLISM RESEARCH AND REVIEWS, 2017, 33(3): e2859.

DOI：10.1002/dmrr.2859

• beta-blocker
• cirrhosis
• glucose tolerance
• hyperinsulinemic-euglycemic clamp
• insulin resistance
• intravenous glucose tolerance test

Background Liver cirrhosis is frequently complicated by portal hypertension leading to increased mortality from variceal bleeding and hepatic decompensation. Noncardioselective beta-blockers 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 beta-blockade with nadolol impairs glucose metabolism in liver cirrhosis.
Methods A randomized, double-blind, placebo-controlled 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-euglycemic clamp for the measurement of insulin secretion and insulin sensitivity (n = 16) and a 75-g oral glucose tolerance test (n = 17). These measurements were conducted twice (after 3 months of treatment with nadolol or placebo and, after a 1-month washout period, after 3 months on the alternative treatment). Total body fat and plasma catecholamines were measured at the end of each 3-month treatment.
Results Compared with placebo, nadolol treatment reduced insulin sensitivity (79.7 +/- 10.1 vs 99.6 +/- 10.3 mu L/kg fat-free mass.min(-1).(mU/L)(-1), P = .005). Insulin secretion was unchanged (P = .24), yielding a lower disposition index with nadolol (6083 +/- 2007 vs 8692 +/- 2036, P = .050). There was no change in total body fat or plasma catecholamines. A 2-hour plasma glucose concentration from the oral glucose tolerance test was higher on nadolol than placebo (10.8 +/- 0.9 vs 9.9 +/- 0.9 mmol/L, P = .035).
Conclusions 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.

• 出版日期2017-3