The online version of this article (doi:10.1186/1475-2840-11-61) contains supplementary material, which is available to authorized users.
The corresponding author and all of the authors have no conflicts of interest or financial or other contractual agreements that might cause conflicts of interest.
MS and DG contributed to the study conception and design. EO was responsible for the data acquisition. MB performed the analysis and interpretation of data. ZM carried out the immunoassays. MS was responsible for review the existing literature and for writing the first draft of the paper. All authors performed a critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.
Insulin resistance (IR) is the major driving force behind development and progression of atherosclerosis in patients with nonalcoholic fatty liver disease (NAFLD). Therefore, correction of IR is a relevant therapeutic target.
We performed the current trial to evaluate whether 12- month metformin therapy improves vascular stiffness in patients with NAFLD and to assess if this improvement is associated with change in glucose control, insulin resistance or circulating adiponectin.
In randomized, placebo controlled study, 63 patients with NAFLD were assigned to one of two groups: Group 1 received daily metformin; Group 2 received placebo. Central aortic augmentation index (AI) was performed using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia) at baseline, at 4-and 12-month treatment period. Metabolic parameters, insulin resistance markers and serum adiponectin levels were determined.
In placebo group: AI did not improve during the treatment period. Liver function and adiponectin levels did not change during the study.
In multiple linear regression analysis, the independent predictors of arterial stiffness improvement were metformin treatment and increase in circulating adiponectin levels.
Among metformin treated patients: AI decreased significantly during the study. ALP and ALT decreased during initial 4-month treatment period, however raised to the pretreatment levels after 12 months. Serum adiponectin level tended to increase during treatment period with metformin.
Metformin treatment was associated with significant decrease in AI during one year treatment in NAFLD patients. These beneficial vascular effects was associated with exposure to metformin per se as well as change in adiponectin levels suggesting that metformin may mediate its vascular effects via glicemic control-independent mechanisms.
Targher G, Bertolini L, Padovani R, Zenari L, Zoppini G, Falezza G: Relation of nonalcoholic hepatic steatosis to early carotid atherosclerosis in healthy men: role of visceral fat accumulation. Diabetes Care. 2004, 7: 1498-1500.
Blaszik H, Ferrentino N, Forsell S, Stander D, Lidofsky S: A pilot study of metformin as treatment for nonalcoholic steatohepatosis. Gastroenterology. 2005, 122: M1699.
Sofer E, Boaz M, Matas Z, Mashavi M, Shargorodsky M: Treatment with insulin sensitizer metformin improves arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial. Metabolism. 2011, 60 (9): 1278-1284. 10.1016/j.metabol.2011.01.011. CrossRefPubMed
UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998, 352: 854-865. CrossRef
de Aguiar LG Kraemer, Bahia LR, Villela N, Laflor C, Sicuro F, Wiernsperger N, Bottino D, Bouskela E: Metformin improves endothelial vascular reactivity in first-degree relatives of type 2 diabetic patients with metabolic syndrome and normal glucose tolerance. Diabetes Care. 2006, 29: 1083-1089. 10.2337/dc05-2146. CrossRefPubMed
Jager J, Kooy A, Lehert PH, Bets D, Wulffele MG, Teerlink T, Scheffer PG, Schalkwijk CG, Donker AJM, Stehouwer CDA: Effect of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controled trial. J Intern Med. 2005, 257: 100-109. 10.1111/j.1365-2796.2004.01420.x. CrossRefPubMed
Grant PJ: Beneficial effects of metformin on haemostasis and vascular function in man. Diabet Med. 2003, 29: 6S44-6S52.
Araki T, Emoto M, Teramura M, Yokoyama H, Mori K, Hatsuda S, Maeno T, Shinohara K, Koyama H, Shoji T, Inaba M, Nishizawa Y: Effect of adiponectin on carotid arterial stiffness in type 2 diabetic patients treated with pioglitazone and metformin. Metabolism. 2006, 55 (8): 996-1001. 10.1016/j.metabol.2006.03.008. CrossRefPubMed
Gomez-Marcos MA, Recio-Rodríguez JI, Patino-Alonso MC, Agudo-Conde C, Gomez-Sanchez L, Rodriguez-Sanchez E, Gomez-Sanchez M, Garcia-Ortiz L: Yearly evolution of organ damage markers in diabetes or metabolic syndrome: data from the LOD-DIABETES study. Cardiovasc Diabetol. 2011, 10: 9-10.1186/1475-2840-10-9. CrossRef
Joy D, Thava VR, Scott BB: Diagnosis of fatty liver disease: is biopsy necessary?. Eur J Gastroenterol Hepatol. 2003, 15: 539-543. PubMed
Meaney E, Vela A, Samaniego V, Meaney A, Asbún J, Zempoalteca JC, Elisa ZN, Emma MN, Guzman M, Hicks J, Ceballos G: Metformin, arterial function, intima-media thickness and nitroxidation in metabolic syndrome: the mefisto study. Clin Exp Pharmacol Physiol. 2008, 35 (8): 895-903. 10.1111/j.1440-1681.2008.04920.x. CrossRefPubMed
Agarwal N, Rice SP, Bolusani H, Luzio SD, Dunseath G, Ludgate M, Rees DA: Metformin reduces arterial stiffness and improves endothelial function in young women with polycystic ovary syndrome: a randomized, placebo-controlled, crossover trial. J Clin Endocrinol Metab. 2010, 95 (2): 722-730. 10.1210/jc.2009-1985. CrossRefPubMed
Kiyici S, Ersoy C, Kaderli A, Fazlioglu M, Budak F, Duran C, Gul OO, Sigirli D, Baran I, Tuncel E, Erturk E, Imamoglu S: Effect of rosiglitazone, metformin and medical nutrition treatment on arterial stiffness, serum MMP-9 and MCP-1 levels in drug naive type 2 diabetic patients. Diabetes Res Clin Pract. 2009, 86 (1): 44-50. 10.1016/j.diabres.2009.07.004. CrossRefPubMed
Huang Y, Fu JF, Shi HB, Liu LR: Metformin prevents non-alcoholic fatty liver disease in rats: role of phospholipase A2/lysophosphatidylcholine lipoapoptosis pathway in hepatocytes]. Zhonghua Er Ke Za Zhi. 2011, 49 (2): 139-145. PubMed
Joel E: Lavine and The TONIC Randomized Controlled Trial: Effect of Vitamin E or Metformin for Treatment of Nonalcoholic Fatty Liver Disease in Children and Adolescents. JAMA. 2011, 305 (16): 1659-1668. 10.1001/jama.2011.520. CrossRef
Krakoff J, Clark JM, Crandall JP, Wilson C, Molitch ME, Brancati FL, Edelstein SL, Knowler WC: Diabetes Prevention Program Research Group. Effects of metformin and weight loss on serum alanine aminotransferase activity in the diabetes prevention program. Obesity (Silver Spring). 2010, 18 (9): 1762-1767. 10.1038/oby.2010.21. CrossRef
Stefan N, Vozarova B, Funahashi T, Matsuzawa Y, Weyer C, Lindsay RS, Youngren JF, Havel PJ, Pratley RE, Bogardus C, Tataranni PA: Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes. 2002, 51: 1884-1888. 10.2337/diabetes.51.6.1884. CrossRefPubMed
Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y: Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000, 96: 1723-1732. PubMed
Kim SG, Kim HY, Seo JA, Lee KW, Oh HJ, Kim NH, Choi CM, Baik SH, Choi DS: Relationship between serum adiponectin concentration, pulse wave velocity and nonalcoholic fatty liver disease. Europ J Endocrinol. 2005, 152: 225-231. 10.1530/eje.1.01842. CrossRef
- Relation between augmentation index and adiponectin during one-year metformin treatment for nonalcoholic steatohepatosis: effects beyond glucose lowering?
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