Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012;7(12):e50117.
doi: 10.1371/journal.pone.0050117. Epub 2012 Dec 6.

Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists

Daniel J Cuthbertson  1 , Andrew Irwin, Chris J Gardner, Christina Daousi, Tej Purewal, Niall Furlong, Niru Goenka, E Louise Thomas, Valerie L Adams, Sudeep P Pushpakom, Munir Pirmohamed, Graham J Kemp
Affiliations

Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists

Daniel J Cuthbertson et al. PLoS One. 2012.

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Upper: Relative changes in liver fat related to relative change in HbA1c (ρ = 0.49; p = 0.01) (left) and absolute change in liver fat related to absolute change in HbA1c (ρ = 0.38; p = 0.06) (right).
Lower: Relative changes in liver fat related to relative change in weight (ρ = 0.21; p = 0.31) (left) and absolute change in liver fat related to absolute change in weight (ρ = −0.04; p = 0.86) (right).
Figure 2
Figure 2. Correlation between changes in liver fat (%) and: Upper: change in total abdominal fat (litres).
Middle: change in abdominal subcutaneous fat (litres). Lower: change in intra-abdominal visceral fat (litres).
Figure 3
Figure 3. Upper Change in liver fat according to weight loss of <5% and >5% and according to relative reduction in HbA1c above or below median (median absolute reduction in HbA1c = 1.3%).
Lower: Change in liver fat according to pre-treatment liver fat percentage (left) and individual plots to demonstrate changes in liver fat ranked by pre-treatment liver fat percentage (right).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Drucker DJ, Nauck MA (2006) The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368: 1696–1705. - PubMed
    1. Jendle J, Nauck MA, Matthews DR, Frid A, Hermansen K, et al. (2009) Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue. Diabetes Obes Metab 11: 1163–1172. - PubMed
    1. Cohen JC, Horton JD, Hobbs HH (2011) Human fatty liver disease: old questions and new insights. Science 332: 1519–1523. - PMC - PubMed
    1. Williamson RM, Price JF, Glancy S, Perry E, Nee LD, et al. (2011) Prevalence of and Risk Factors for Hepatic Steatosis and Nonalcoholic Fatty Liver Disease in People With Type 2 Diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes Care 34: 1139–1144. - PMC - PubMed
    1. Kotronen A, Juurinen L, Hakkarainen A, Westerbacka J, (null), et al (2007) Liver fat is increased in type 2 diabetic patients and underestimated by serum alanine aminotransferase compared with equally obese nondiabetic subjects. Diabetes Care 31: 165–169. - PubMed

Publication types

MeSH terms

Grants and funding

Funding from medical charity Weight Matters was for £2500. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Please note this charity is a local charity set up by the investigators and the volunteers within the authors' hospital and they contributed £2500 towards cost of MRI scanning.