title: Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists.
abstract: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective for obese patients with type 2 diabetes mellitus (T2DM) because they concomitantly target obesity and dysglycaemia. Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with T2DM, we determined the impact of 6 months' GLP-1 RA therapy on intrahepatic lipid (IHL) in obese, T2DM patients with hepatic steatosis, and evaluated the inter-relationship between changes in IHL with those in glycosylated haemoglobin (HbA(1)c), body weight, and volume of abdominal visceral and subcutaneous adipose tissue (VAT and SAT). We prospectively studied 25 (12 male) patients, age 50±10 years, BMI 38.4±5.6 kg/m(2) (mean ± SD) with baseline IHL of 28.2% (16.5 to 43.1%) and HbA(1)c of 9.6% (7.9 to 10.7%) (median and interquartile range). Patients treated with metformin and sulphonylureas/DPP-IV inhibitors were given 6 months GLP-1 RA (exenatide, n = 19; liraglutide, n = 6). IHL was quantified by liver proton magnetic resonance spectroscopy ((1)H MRS) and VAT and SAT by whole body magnetic resonance imaging (MRI). Treatment was associated with mean weight loss of 5.0 kg (95% CI 3.5,6.5 kg), mean HbA(1c) reduction of 1·6% (17 mmol/mol) (0·8,2·4%) and a 42% relative reduction in IHL (-59.3, -16.5%). The relative reduction in IHL correlated with that in HbA(1)c (ρ = 0.49; p = 0.01) but was not significantly correlated with that in total body weight, VAT or SAT. The greatest IHL reduction occurred in individuals with highest pre-treatment levels. Mechanistic studies are needed to determine potential direct effects of GLP-1 RA on human liver lipid metabolism.
authors.affiliation: Department of Obesity and Endocrinology, University Hospital Aintree, Liverpool, Liverpool, United Kingdom. daniel.cuthbertson@liverpool.ac.uk
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cuthbertson
authors.forename: Andrew
authors.initials: A
authors.lastname: Irwin
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Gardner
authors.forename: Christina
authors.initials: C
authors.lastname: Daousi
authors.forename: Tej
authors.initials: T
authors.lastname: Purewal
authors.forename: Niall
authors.initials: N
authors.lastname: Furlong
authors.forename: Niru
authors.initials: N
authors.lastname: Goenka
authors.forename: E Louise
authors.initials: EL
authors.lastname: Thomas
authors.forename: Valerie L
authors.initials: VL
authors.lastname: Adams
authors.forename: Sudeep P
authors.initials: SP
authors.lastname: Pushpakom
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Kemp
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects*; D015992:Body Mass Index; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D000077270:Exenatide; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000819:agonists* / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000627:therapeutic use; D011446:Prospective Studies; D014688:Venoms / Q000627:therapeutic use; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide