Improved Glycaemia Correlates with Liver Fat Reduction in Obese, Type 2 Diabetes, Patients Given Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists

PLoS ONE

Volumn 7, Issue 12, 2012, Pages

  Cuthbertson, Daniel J ^a,b   Irwin, Andrew ^a   Gardner, Chris J ^a   Daousi, Christina ^a,b   Purewal, Tej ^c   Furlong, Niall ^d   Goenka, Niru ^e   Thomas, E Louise ^f   Adams, Valerie L ^b   Pushpakom, Sudeep P ^b   Pirmohamed, Munir ^b   Kemp, Graham J ^b  

^a UNIVERSITY HOSPITAL AINTREE   (United Kingdom)

^b UNIVERSITY OF LIVERPOOL   (United Kingdom)

^c ROYAL LIVERPOOL UNIVERSITY HOSPITAL   (United Kingdom)

^d Department of Diabetes and Endocrinology St Helen's and Knowsley ^*  (United Kingdom)

^e Countess of Chester Hospital ^*  (United Kingdom)

^f IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPONECTIN; ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; EXENDIN 4; GAMMA GLUTAMYLTRANSFERASE; GLICLAZIDE; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; HEMOGLOBIN A1C; LIRAGLUTIDE; METFORMIN; SITAGLIPTIN;

ADULT; ARTICLE; BODY MASS; CLINICAL ARTICLE; DRUG DOSE INCREASE; DRUG DOSE TITRATION; FATTY LIVER; FEMALE; GLYCEMIC CONTROL; HUMAN; INTRAABDOMINAL FAT; LIPID LIVER LEVEL; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PROSPECTIVE STUDY; PROTON NUCLEAR MAGNETIC RESONANCE; SOLEUS MUSCLE; SUBCUTANEOUS FAT; TIBIALIS ANTERIOR MUSCLE; WEIGHT REDUCTION; WHOLE BODY MRI;

ADIPOSITY; ADULT; BLOOD GLUCOSE; BODY MASS INDEX; BODY WEIGHT; DIABETES MELLITUS, TYPE 2; FATTY LIVER; FEMALE; GLUCAGON-LIKE PEPTIDE 1; HUMANS; HYPOGLYCEMIC AGENTS; LIVER; MALE; MIDDLE AGED; OBESITY; PEPTIDES; PROSPECTIVE STUDIES; VENOMS; WEIGHT LOSS;

EID: 84870817823     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0050117     Document Type: Article

References (38)

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.
2. 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.
3. Cohen JC, Horton JD, Hobbs HH, (2011) Human fatty liver disease: old questions and new insights. Science 332: 1519-1523.
4. 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.
5. 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.
6. Targher G, Bertolini L, Poli F, Rodella S, Scala L, et al. (2005) Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 54: 3541-3546.
7. Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, et al. (2005) Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab 288: E462-E468.
8. Shlomo SB, Zvibel I, Shnell M, Shlomai A, Chepurko E, et al. (2010) Glucagon-Like Peptide-1 reduces hepatic lipogenesis via activation of AMP-activated Protein Kinase. J Hepatol.
9. Kotronen A, Juurinen L, Tiikkainen M, Vehkavaara S, Yki-Järvinen H, (2008) Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. Gastroenterology 135: 122-130.
10. Svegliati-Baroni G, Saccomanno S, Rychlicki C, Agostinelli L, De Minicis S, et al. (2011) Glucagon-like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high-fat diet in nonalcoholic steatohepatitis. Liver International 31: 1285-1297.
11. Gupta NA, Mells J, Dunham RM, Grakoui A, Handy J, et al. (2010) Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway. Hepatology 51: 1584-1592.
12. de Marco R, Locatelli F, Zoppini G, Verlato G, Bonora E, et al. (1999) Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study. Diabetes Care 22: 756-761.
13. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, et al. (2005) Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115: 1343-1351.
14. Targher G, Bertolini L, Padovani R, Poli F, Scala L, et al. (2006) Increased prevalence of cardiovascular disease in Type 2 diabetic patients with non-alcoholic fatty liver disease. Diabet Med 23: 403-409.
15. Targher G, Marra F, Marchesini G, (2008) Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon? Diabetologia 51: 1947-1953.
16. Targher G, Bertolini L, Rodella S, Zoppini G, Lippi G, et al. (2008) Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients. Diabetologia 51: 444-450.
17. Bajaj M, Suraamornkul S, Piper P, Hardies LJ, Glass L, et al. (2004) Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients. Journal of Clinical Endocrinology & Metabolism 89: 200-206.
18. Harrison SA, Day CP, (2007) Benefits of lifestyle modification in NAFLD. Gut 56: 1760-1769.
19. Bugianesi E, Bugianesi E, (2005) Plasma Adiponectin in Nonalcoholic Fatty Liver Is Related to Hepatic Insulin Resistance and Hepatic Fat Content, Not to Liver Disease Severity. Journal of Clinical Endocrinology & Metabolism 90: 3498-3504.
20. Lazo M, Solga SF, Horska A, Bonekamp S, Diehl AM, et al. (2010) Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes. Diabetes Care 33: 2156-2163.
21. Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, et al. (2005) Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 54: 603-608.
22. Ratziu V, Caldwell S, Neuschwander-Tetri BA, (2010) Therapeutic trials in nonalcoholic steatohepatitis: insulin sensitizers and related methodological issues. Hepatology 52: 2206-2215.
23. Tiikkainen M, Häkkinen A-M, Korsheninnikova E, Nyman T, Mäkimattila S, et al. (2004) Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 53: 2169-2176.
24. Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, et al. (2005) A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 100: 1082-1090.
25. Belfort R, Harrison SA, Brown K, Darland C, Finch J, et al. (2006) A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 355: 2297-2307.
26. Buse JB, Klonoff DC, Nielsen LL, Guan X, Bowlus CL, et al. (2007) Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther 29: 139-153.
27. Tushuizen ME, Bunck MC, Pouwels PJ, van Waesberghe JHT, Diamant M, et al. (2006) Incretin mimetics as a novel therapeutic option for hepatic steatosis. Liver Int 26: 1015-1017.
28. Kenny PR, Brady DE, Torres DM, Ragozzino L, Chalasani N, et al. (2010) Exenatide in the treatment of diabetic patients with non-alcoholic steatohepatitis: a case series. Am J Gastroenterol 105: 2707-2709.
29. Centre for Clinical Practice at NICE (UK) (2009) Type 2 Diabetes: Newer Agents for Blood Glucose Control in Type 2 Diabetes. London: National Institute for Health and Clinical Excellence (UK).
30. Gardner CJ, Richardson P, Wong C, Polavarapu N, Kemp GJ, et al. (2011) Hypothyroidism in a patient with non-alcoholic fatty liver disease. BMJ 342: c7199.
31. Thomas EL, Hamilton G, Patel N, O'Dwyer R, Doré CJ, et al. (2005) Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study. Gut 54: 122-127.
32. Szczepaniak LS, Babcock EE, Schick F, Dobbins RL, Garg A, et al. (1999) Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo. Am J Physiol 276: E977-E989.
33. Bunck MC, Diamant M, Eliasson B, (null), Shaginian RM, et al (2010) Exenatide affects circulating cardiovascular risk biomarkers independently of changes in body composition. Diabetes Care 33: 1734-1737.
34. Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, et al. (2009) Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). The Lancet 374: 39-47.
35. Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, et al. (2011) Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 54: 2506-2514.
36. Bajaj M, Suraamornkul S, Pratipanawatr T, Hardies LJ, Pratipanawatr W, et al. (2003) Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes 52: 1364-1370.
37. Sathyanarayana P, Jogi M, Muthupillai R, Krishnamurthy R, Samson SL, et al. (2011) Effects of Combined Exenatide and Pioglitazone Therapy on Hepatic Fat Content in Type 2 Diabetes. Obesity (Silver Spring).
38. Hattersley JG, Möhlig M, Roden M, Arafat AM, Loeffelholz CV, et al. (2012) Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques. PLoS ONE 7: e39029.