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Effects of acute glucocorticoid blockade on metabolic dysfunction in patients with type 2 diabetes with and without fatty liver

Lookup NU author(s): Professor Brian WalkerORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2014 the American Physiological Society. To investigate the potential of therapies which reduce glucocorticoid action in patients with Type 2 diabetes we performed a randomized, double-blinded, placebo-controlled crossover study of acute glucocorticoid blockade, using the glucocorticoid receptor antagonist RU38486 (mifepristone) and cortisol biosynthesis inhibitor (metyrapone), in 14 men with Type 2 diabetes. Stable isotope dilution methodologies were used to measure the rates of appearance of glucose, glycerol, and free fatty acids (FFAs), including during a low-dose (10 mU·m 2·min 1) hyperinsulinemic clamp, and subgroup analysis was conducted in patients with high or low liver fat content measured by magnetic resonance spectroscopy (n 7/group). Glucocorticoid blockade lowered fasting glucose and insulin levels and improved insulin sensitivity of FFA and glycerol turnover and hepatic glucose production. Among this population with Type 2 diabetes high liver fat was associated with hyperinsulinemia, higher fasting glucose levels, peripheral and hepatic insulin resistance, and impaired suppression of FFA oxidation and FFA and glycerol turnover during hyperinsulinemia. Glucocorticoid blockade had similar effects in those with and without high liver fat. Longer term treatments targeting glucocorticoid action may be useful in Type 2 diabetes with and without fatty liver.

Publication metadata

Author(s): Macfarlane DP, Raubenheimer PJ, Preston T, Gray CD, Bastin ME, Marshall I, Iredale JP, Andrew R, Walker BR

Publication type: Article

Publication status: Published

Journal: American Journal of Physiology - Gastrointestinal and Liver Physiology

Year: 2014

Volume: 307

Issue: 7

Pages: G760-G768

Print publication date: 01/10/2014

Online publication date: 01/10/2014

Acceptance date: 16/07/2014

Date deposited: 02/02/2018

ISSN (print): 0193-1857

ISSN (electronic): 1522-1547

Publisher: American Physiological Society

URL: https://doi.org/10.1152/ajpgi.00030.2014

DOI: 10.1152/ajpgi.00030.2014

PubMed id: 25104497

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