The role of metformin in the management of NAFLD

Experimental Diabetes Research

Volumn 2012, Issue , 2012, Pages

  Mazza, Angela ^a   Fruci, Barbara ^a   Garinis, Giorgia Anna ^a   Giuliano, Stefania ^a   Malaguarnera, Roberta ^a   Belfiore, Antonino ^a  

^a UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; 3 HYDROXY 3 METHYLGLUTARYL COENZYME A; ACETYL COENZYME A CARBOXYLASE; ALANINE AMINOTRANSFERASE; AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN BINDING PROTEIN; FATTY ACID SYNTHASE; GLUCOSE 6 PHOSPHATASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LIVER ENZYME; METFORMIN; PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP); PIOGLITAZONE; POLICOSANOL; ROSIGLITAZONE; SATURATED FATTY ACID; SILYMARIN; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR ALPHA; ANTIDIABETIC AGENT;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ATHEROSCLEROSIS; BODY MASS; DIET; ENDOPLASMIC RETICULUM; EXERCISE; HEPATITIS; HUMAN; HYPERLIPIDEMIA; HYPERTENSION; HYPERURICEMIA; INSULIN RESISTANCE; LIFESTYLE MODIFICATION; LIVER BIOPSY; LOW CALORY DIET; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; OBESITY; OVARY POLYCYSTIC DISEASE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; RISK FACTOR; STEATOSIS; VULVA DISEASE; WEIGHT CONTROL; FATTY LIVER;

FATTY LIVER; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN RESISTANCE; METFORMIN;

EID: 84855572961     PISSN: 16875214     EISSN: 16875303     Source Type: Journal    
DOI: 10.1155/2012/716404     Document Type: Review

References (113)

1. Festi D., Colecchia A., Sacco T., Bondi M., Roda E., Marchesini G., Hepatic steatosis in obese patients: clinical aspects and prognostic significance Obesity Reviews 2004 5 1 27 42 (Pubitemid 38173592)
2. Marchesini G., Bugianesi E., Forlani G., Cerrelli F., Lenzi M., Manini R., Natale S., Vanni E., Villanova N., Melchionda N., Rizzetto M., Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome Hepatology 2003 37 4 917 923 (Pubitemid 36397405)
3. Loria P., Lonardo A., Bellentani S., Day C. P., Marchesini G., Carulli N., Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease: an open question Nutrition, Metabolism and Cardiovascular Diseases 2007 17 9 684 698 (Pubitemid 47593074)
4. de Alwis N. M. W., Day C. P., Non-alcoholic fatty liver disease: the mist gradually clears Journal of Hepatology 2008 48 supplement 1 S104 S112
5. Socha P., Horvath A., Vajro P., Dziechciarz P., Dhawan A., Szajewska H., Pharmacological interventions for nonalcoholic fatty liver disease in adults and in children: a systematic review Journal of Pediatric Gastroenterology and Nutrition 2009 48 5 587 596
6. Schwimmer J. B., Khorram O., Chiu V., Schwimmer W. B., Abnormal aminotransferase activity in women with polycystic ovary syndrome Fertility and Sterility 2005 83 2 494 497 (Pubitemid 40221817)
7. Setji T. L., Holland N. D., Sanders L. L., Pereira K. C., Diehl A. M., Brown A. J., Nonalcoholic steatohepatitis and nonalcoholic fatty liver disease in young women with polycystic ovary syndrome Journal of Clinical Endocrinology and Metabolism 2006 91 5 1741 1747
8. Angulo P., Medical progress: nonalcoholic fatty liver disease The New England Journal of Medicine 2002 346 16 1221 1231 (Pubitemid 34984585)
9. Day C. P., James O. F. W., Steatohepatitis: a tale of two 'Hits'? Gastroenterology 1998 114 4 842 845 (Pubitemid 28160420)
10. Matsuzawa N., Takamura T., Kurita S., Misu H., Ota T., Ando H., Yokoyama M., Honda M., Zen Y., Nakanuma Y., Miyamoto K. I., Kaneko S., Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet Hepatology 2007 46 5 1392 1403 (Pubitemid 350155521)
11. Gentile C. L., Pagliassotti M. J., The role of fatty acids in the development and progression of nonalcoholic fatty liver disease Journal of Nutritional Biochemistry 2008 19 9 567 576
12. Stefan N., Hring H.-U., The metabolically benign and malignant fatty liver Diabetes 2011 60 8 2011 2017
13. Mofrad P., Contos M. J., Haque M., Sargeant C., Fisher R. A., Luketic V. A., Sterling R. K., Shiffman M. L., Stravitz R. T., Sanyal A. J., Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values Hepatology 2003 37 6 1286 1292 (Pubitemid 36667307)
14. Stefan N., Kantartzis K., Machann J., Schick F., Thamer C., Rittig K., Balletshofer B., Machicao F., Fritsche A., Hring H. U., Identification and characterization of metabolically benign obesity in humans Archives of Internal Medicine 2008 168 15 1609 1616
15. Fabbrini E., Magkos F., Mohammed B. S., Pietka T., Abumrad N. A., Patterson B. W., Okunade A., Klein S., Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity Proceedings of the National Academy of Sciences of the United States of America 2009 106 36 15430 15435
16. Akbar D. H., Kawther A. H., Non-alcoholic fatty liver disease and metabolic syndrome: what we know and what we don't know Medical Science Monitor 2006 12 1 RA23 RA26
17. Browning J. D., Szczepaniak L. S., Dobbins R., Nuremberg P., Horton J. D., Cohen J. C., Grundy S. M., Hobbs H. H., Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity Hepatology 2004 40 6 1387 1395 (Pubitemid 39657013)
18. Kotronen A., Westerbacka J., Bergholm R., Pietilainen K. H., Yki-Jarvinen H., Liver fat in the metabolic syndrome The Journal of Clinical Endocrinology Metabolism 2007 92 3490 3497 (Pubitemid 47435325)
19. Wieckowska A., McCullough A. J., Feldstein A. E., Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future Hepatology 2007 46 2 582 589 (Pubitemid 47344794)
20. Hamaguchi M., Kojima T., Takeda N., Nakagawa T., Taniguchi H., Fujii K., Omatsu T., Nakajima T., Sarui H., Shimazaki M., Kato T., Okuda J., Ida K., The metabolic syndrome as a predictor of nonalcoholic fatty liver disease Annals of Internal Medicine 2005 143 10 722 728
21. Tobari M., Hashimoto E., Yatsuji S., Torii N., Shiratori K., Imaging of nonalcoholic steatohepatitis: advantages and pitfalls of ultrasonography and computed tomography Internal Medicine 2009 48 10 739 746
22. Dasarathy S., Dasarathy J., Khiyami A., Joseph R., Lopez R., McCullough A. J., Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study Journal of Hepatology 2009 51 6 1061 1067
23. Vuppalanchi R., Chalasani N., Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: selected practical issues in their evaluation and management Hepatology 2009 49 1 306 317
24. Yamauchi T., Kamon J., Minokoshi Y., Ito Y., Waki H., Uchida S., Yamashita S., Noda M., Kita S., Ueki K., Eto K., Akanuma Y., Froguel P., Foufelle F., Ferre P., Carling D., Kimura S., Nagai R., Kahn B. B., Kadowaki T., Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase Nature Medicine 2002 8 11 1288 1295 (Pubitemid 35373562)
25. Tsochatzis E. A., Papatheodoridis G. V., Archimandritis A. J., Adipokines in nonalcoholic steatohepatitis: from pathogenesis to implications in diagnosis and therapy Mediators of Inflammation 2009 2009 8
26. Tiniakos D. G., Vos M. B., Brunt E. M., Nonalcoholic fatty liver disease: pathology and pathogenesis Annual Review of Pathology 2010 5 145 171
27. Yoneda M., Fujita K., Inamori M., Nakajima A., Yoneda M., Tamano M., Hiraishi H., Transient elastography in patients with non-alcoholic fatty liver disease (NAFLD) Gut 2007 56 9 1330 1331 (Pubitemid 47300449)
28. Angulo P., Hui J. M., Marchesini G., Bugianesi E., George J., Farrell G. C., Enders F., Saksena S., Burt A. D., Bida J. P., Lindor K., Sanderson S. O., Lenzi M., Adams L. A., Kench J., Therneau T. M., Day C. P., The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD Hepatology 2007 45 4 846 854 (Pubitemid 46631552)
29. Ratziu V., Giral P., Charlotte F., Bruckert E., Thibault V., Theodorou I., Khalil L., Turpin G., Opolon P., Poynard T., Liver fibrosis in overweight patients Gastroenterology 2000 118 6 1117 1123 (Pubitemid 30346988)
30. Dixon J. B., Bhathal P. S., O'Brien P. E., Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese Gastroenterology 2001 121 1 91 100 (Pubitemid 32591518)
31. Huang M. A., Greenson J. K., Chao C., Anderson L., Peterman D., Jacobson J., Emick D., Lok A. S., Conjeevaram H. S., One-year intense nutritional counseling results in histological improvement in patients with nonalcoholic steatohepatitis: a pilot study American Journal of Gastroenterology 2005 100 5 1072 1081 (Pubitemid 40769044)
32. Palmer M., Schaffner F., Effect of weight reduction on hepatic abnormalities in overweight patients Gastroenterology 1990 99 5 1408 1413 (Pubitemid 20381878)
33. Wang R. T., Koretz R. L., Yee H. F. Jr., Is weight reduction an effective therapy for nonalcoholic fatty liver? A systematic review American Journal of Medicine 2003 115 7 554 559 (Pubitemid 37352802)
34. Kadayifci A., Merriman R. B., Bass N. M., Medical treatment of non-alcoholic steatohepatitis Clinics in Liver Disease 2007 11 1 119 140 (Pubitemid 46829966)
35. Garinis G. A., Fruci B., Mazza A., De Siena M., Abenavoli S., Gulletta E., Ventura V., Greco M., Abenavoli L., Belfiore A., Metformin versus dietary treatment in nonalcoholic hepatic steatosis: a randomized study International Journal of Obesity 2010 34 8 1255 1264
36. Marlatt G. A., Larimer M. E., Mail P. D., Hawkins E. H., Cummins L. H., Blume A. W., Lonczak H. S., Burns K. M., Chan K. K., Cronce J. M., La Marr C. J., Radin S., Forquera R., Gonzales R., Tetrick C., Gallion S., Journeys of the circle: a culturally congruent life skills intervention for adolescent Indian drinking Alcoholism 2003 27 8 1327 1329 (Pubitemid 36999227)
37. Tiikkainen M., Hkkinen A. M., Korsheninnikova E., Nyman T., Mkimattila S., Yki-Jrvinen H., 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 2004 53 8 2169 2176 (Pubitemid 38970772)
38. Ratziu V., Giral P., Jacqueminet S., Charlotte F., Hartemann-Heurtier A., Serfaty L., Podevin P., Lacorte J. M., Bernhardt C., Bruckert E., Grimaldi A., Poynard T., Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial Gastroenterology 2008 135 1 100 110 (Pubitemid 351916703)
39. Sanyal A. J., Mofrad P. S., Contos M. J., Sargeant C., Luketic V. A., Sterling R. K., Stravitz R. T., Shiffman M. L., Clore J., Mills A. S., A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis Clinical Gastroenterology and Hepatology 2004 2 12 1107 1115 (Pubitemid 40037642)
40. Belfort R., Harrison S. A., Brown K., Darland C., Finch J., Hardies J., Balas B., Gastaldelli A., Tio F., Pulcini J., Berria R., Ma J. Z., Dwivedi S., Havranek R., Fincke C., DeFronzo R., Bannayan G. A., Schenker S., Cusi K., A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis The New England Journal of Medicine 2006 355 22 2297 2307 (Pubitemid 44837778)
41. Aithal G. P., Thomas J. A., Kaye P. V., Lawson A., Ryder S. D., Spendlove I., Austin A. S., Freeman J. G., Morgan L., Webber J., Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis Gastroenterology 2008 135 4 1176 1184
42. Promrat K., Kleiner D. E., Niemeier H. M., Jackvony E., Kearns M., Wands J. R., Fava J. L., Wing R. R., Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis Hepatology 2010 51 1 121 129
43. Sanyal A. J., Chalasani N., Kowdley K. V., McCullough A., Diehl A. M., Bass N. M., Neuschwander-Tetri B. A., Lavine J. E., Tonascia J., Unalp A., Van Natta M., Clark J., Brunt E. M., Kleiner D. E., Hoofnagle J. H., Robuck P. R., Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis The New England Journal of Medicine 2010 362 18 1675 1685
44. Chaffer C. L., Thomas D. M., Thompson E. W., Williams E. D., PPAR -independent induction of growth arrest and apoptosis in prostate and bladder carcinoma BMC Cancer 2006 6, article 53
45. He L., Sabet A., Djedjos S., Miller R., Sun X., Hussain M. A., Radovick S., Wondisford F. E., Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein Cell 2009 137 4 635 646
46. Stumvoll M., Nurjhan N., Perriello G., Dailey G., Gerich J. E., Metabolic effects of metformin in non-insulin-dependent diabetes mellitus The New England Journal of Medicine 1995 333 9 550 554
47. Loomba R., Lutchman G., Kleiner D. E., Ricks M., Feld J. J., Borg B. B., Modi A., Nagabhyru P., Sumner A. E., Liang T. J., Hoofnagle J. H., Clinical trial: pilot study of metformin for the treatment of non-alcoholic steatohepatitis Alimentary Pharmacology and Therapeutics 2009 29 2 172 182
48. Kohjima M., Higuchi N., Kato M., Kotoh K., Yoshimoto T., Fujino T., Yada M., Yada R., Harada N., Enjoji M., Takayanagi R., Nakamuta M., SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease International Journal of Molecular Medicine 2008 21 4 507 511 (Pubitemid 351802646)
49. Huypens P., Quartier E., Pipeleers D., Van De Casteele M., Metformin reduces adiponectin protein expression and release in 3T3-L1 adipocytes involving activation of AMP activated protein kinase European Journal of Pharmacology 2005 518 2-3 90 95 (Pubitemid 41133630)
50. Lin H. Z., Yang S. Q., Chuckaree C., Kuhajda F., Ronnet G., Diehl A. M., Metformin reverses fatty liver disease in obese, leptin-deficient mice Nature Medicine 2000 6 9 998 1003
51. Zhang S., Liu X., Brickman W. J., Christoffel K. K., Zimmerman D., Tsai H. J., Wang G., Wang B., Li Z., Tang G., Liu X., Yang J., Xu X., Wang X., Association of plasma leptin concentrations with adiposity measurements in rural Chinese adolescents Journal of Clinical Endocrinology and Metabolism 2009 94 9 3497 3504
52. Marchesini G., Brizi M., Bianchi G., Tomassetti S., Zoli M., Melchionda N., Metformin in non-alcoholic steatohepatitis Lancet 2001 358 9285 893 894 (Pubitemid 32900577)
53. Nair S., Diehl A. M., Wiseman M., Farr G. H. Jr., Perrillo R. P., Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial Alimentary Pharmacology and Therapeutics 2004 20 1 23 28 (Pubitemid 38938715)
54. Uygun A., Kadayifci A., Isik A. T., Ozgurtas T., Deveci S., Tuzun A., Yesilova Z., Gulsen M., Dagalp K., Metformin in the treatment of patients with non-alcoholic steatohepatitis Alimentary Pharmacology and Therapeutics 2004 19 5 537 544 (Pubitemid 38387180)
55. Bugianesi E., Gentilcore E., Manini R., Natale S., Vanni E., Villanova N., David E., Rizzetto M., Marchesini G., A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease American Journal of Gastroenterology 2005 100 5 1082 1090 (Pubitemid 40769045)
56. Duseja A., Das A., Dhiman R. K., Chawla Y. K., Thumburu K. K., Bhadada S., Bhansali A., Metformin is effective in achieving biochemical response in patients with nonalcoholic fatty liver disease (NAFLD) not responding to lifestyle interventions Annals of Hepatology 2007 6 4 222 226
57. de Oliveira C. P. M. S., Stefano J. T., De Siqueira E. R. F., Silva L. S., de Campos Mazo D. F., Lima V. M. R., Furuya C. K., Mello E. S., Souza F. G., Rabello F., Santos T. E., Nogueira M. A., Caldwell S. H., Alves V. A. F., Carrilho F. J., Combination of N-acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non-alcoholic steatohepatitis Hepatology Research 2008 38 2 159 165
58. Idilman R., Mizrak D., Corapcioglu D., Bektas M., Doganay B., Sayki M., Coban S., Erden E., Soykan I., Emral R., Uysal A. R., Ozden A., Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis Alimentary Pharmacology and Therapeutics 2008 28 2 200 208 (Pubitemid 351861962)
59. Haukeland J. W., Konopski Z., Eggesb H. B., Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial Scandinavian Journal of Gastroenterology 2009 44 7 853 860
60. Janiec D. J., Jacobson E. R., Freeth A., Spaulding L., Blaszyk H., Histologic variation of grade and stage of non-alcoholic fatty liver disease in liver biopsies Obesity Surgery 2005 15 4 497 501 (Pubitemid 40605072)
61. Omer Z., Cetinkalp S., Akyildiz M., Yilmaz F., Batur Y., Yilmaz C., Akarca U., Efficacy of insulin-sensitizing agents in nonalcoholic fatty liver disease European Journal of Gastroenterology and Hepatology 2010 22 1 18 23
62. Nar A., Gedik O., The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease Acta Diabetologica 2009 46 2 113 118
63. Schwimmer J. B., Behling C., Newbury R., Deutsch R., Nievergelt C., Schork N. J., Lavine J. E., Histopathology of pediatric nonalcoholic fatty liver disease Hepatology 2005 42 3 641 649 (Pubitemid 41233657)
64. Nadeau K. J., Ehlers L. B., Zeitler P. S., Love-Osborne K., Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents Pediatric Diabetes 2009 10 1 5 13
65. Nobili V., Marcellini M., Devito R., Ciampalini P., Piemonte F., Comparcola D., Sartorelli M. R., Angulo P., NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice Hepatology 2006 44 2 458 465 (Pubitemid 44214885)
66. Lavine J. E., Schwimmer J. B., Molleston J. P., Scheimann A. O., Murray K. F., Abrams S. H., Rosenthal P., Sanyal A. J., Robuck P. R., Brunt E. M., nalp A., Tonascia J., Treatment of nonalcoholic fatty liver disease in children: TONIC trial design Contemporary Clinical Trials 2010 31 1 62 70
67. Kirpichnikov D., McFarlane S. I., Sowers J. R., Metformin: an update Annals of Internal Medicine 2002 137 1 25 33 (Pubitemid 34705373)
68. Landin K., Tengborn L., Smith U., Treating insulin resistance inhypertension with metformin reduces both blood pressure and metabolic risk factors Journal of Internal Medicine 1991 229 2 181 187
69. Petersen J. S., DiBona G. F., Acute sympathoinhibitory actions of metformin in spontaneously hypertensive rats Hypertension 1996 27 3 619 625 (Pubitemid 26086229)
70. Morrow V. A., Foufelle F., Connell J. M. C., Petrie J. R., Gould G. W., Salt I. P., Direct activation of AMP-activated protein kinase stimulates nitric-oxide synthesis in human aortic endothelial cells Journal of Biological Chemistry 2003 278 34 31629 31639 (Pubitemid 37048341)
71. Fabbrini E., Sullivan S., Klein S., Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications Hepatology 2010 51 2 679 689
72. Johansen K., Efficacy of metformin in the treatment of NIDDM: meta-analysis Diabetes Care 1999 22 1 33 37 (Pubitemid 29028295)
73. Haupt E., Knick B., Koschinsky T., Liebermeister H., Schneider J., Hirche H., Oral antidiabetic combination therapy with sulphonylureas and metformin Diabete et Metabolisme 1991 17 1 224 231
74. Pasquali R., Gambineri A., Biscotti D., Vicennati V., Gagliardi L., Colitta D., Fiorini S., Cognigni G. E., Filicori M., Morselli-Labate A. M., Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome Journal of Clinical Endocrinology and Metabolism 2000 85 8 2767 2774 (Pubitemid 32269149)
75. Glueck C. J., Wang P., Fontaine R., Tracy T., Sieve-Smith L., Metformin-induced resumption of normal menses in 39 of 43 (91) previously amenorrheic women with the polycystic ovary syndrome Metabolism: Clinical and Experimental 1999 48 4 511 519 (Pubitemid 29174233)
76. Yki-Jrvinen H., Nikkil K., Mkimattila S., Metformin prevents weight gain by reducing dietary intake during insulin therapy in patients with type 2 diabetes mellitus Drugs 1999 58 supplement 1 53 54
77. Sowers J. R., Obesity and cardiovascular disease Clinical Chemistry 1998 44 8 1821 1825 (Pubitemid 28368902)
78. Effects of withdrawal from metformin on the development of diabetes in the diabetes prevention program Diabetes Care 2003 26 4 977 980
79. McFarlane S. I., Banerji M., Sowers J. R., Insulin resistance and cardiovascular disease Journal of Clinical Endocrinology and Metabolism 2001 86 2 713 718 (Pubitemid 32207485)
80. Hickman I. J., Jonsson J. R., Prins J. B., Ash S., Purdie D. M., Clouston A. D., Powell E. E., Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life Gut 2004 53 3 413 419 (Pubitemid 38241340)
81. Larson-Meyer D. E., Newcomer B. R., Heilbronn L. K., Volaufova J., Smith S. R., Alfonso A. J., Lefevre M., Rood J. C., Williamson D. A., Ravussin E., DeLany J., De Jonge L., Nguyen T., Martin C. K., Most M. M., Greenway F. L., York-Crow E., Anton S., Champagne C., Dahmer B., Deutsch A., Geiselman P., Howard J., Ihrig J., Marquis D., Murla C., Owens S., Stewart A., Tarver V., Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function Obesity 2008 16 6 1355 1362 (Pubitemid 351770499)
82. Krakoff J., Clark J. M., Crandall J. P., Wilson C., Molitch M. E., Brancati F. L., Edelstein S. L., Knowler W. C., Effects of metformin and weight loss on serum alanine aminotransferase activity in the diabetes prevention program Obesity 2010 18 9 1762 1767
83. Knowler W. C., Barrett-Connor E., Fowler S. E., Hamman R. F., Lachin J. M., Walker E. A., Nathan D. M., Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin The New England Journal of Medicine 2002 346 6 393 403 (Pubitemid 34437694)
84. Diamanti-Kandarakis E., Polycystic ovarian syndrome: pathophysiology, molecular aspects and clinical implications Expert Reviews in Molecular Medicine 2008 10 3 1 21 (Pubitemid 351338213)
85. Gutierrez-Grobe Y., Ponciano-Rodrguez G., Ramos M. H., Uribe M., Méndez-Snchez N., Prevalence of non alcoholic fatty liver disease in premenopausal, posmenopausal and polycystic ovary syndrome women. The role of estrogens Annals of Hepatology 2010 9 4 402 409
86. Chodick G., Heymann A. D., Rosenmann L., Green M. S., Flash S., Porath A., Kokia E., Shalev V., Diabetes and risk of incident cancer: a large population-based cohort study in Israel Cancer Causes and Control 2010 21 6 879 887
87. Vigneri P., Frasca F., Sciacca L., Frittitta L., Vigneri R., Obesity and cancer Nutrition, Metabolism and Cardiovascular Diseases 2006 16 1 1 7
88. Strickler H. D., Wylie-Rosett J., Rohan T., Hoover D. R., Smoller S., Burk R. D., Yu H., The relation of type 2 diabetes and cancer Diabetes Technology and Therapeutics 2001 3 2 263 274 (Pubitemid 32651962)
89. Coughlin S. S., Calle E. E., Teras L. R., Petrelli J., Thun M. J., Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults American Journal of Epidemiology 2004 159 12 1160 1167 (Pubitemid 38747263)
90. Renehan A. G., Tyson M., Egger M., Heller R. F., Zwahlen M., Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies The Lancet 2008 371 9612 569 578 (Pubitemid 351232031)
91. Cantrell L. A., Zhou C., Mendivil A., Malloy K. M., Gehrig P. A., Bae-Jump V. L., Metformin is a potent inhibitor of endometrial cancer cell proliferation-implications for a novel treatment strategy Gynecologic Oncology 2010 116 1 92 98
92. Vainio H., Kaaks R., Bianchini F., Weight control and physical activity in cancer prevention: international evaluation of the evidence European Journal of Cancer Prevention 2002 11 supplement 2 S94 S100
93. Belfiore A., Frasca F., IGF and insulin receptor signaling in breast cancer Journal of Mammary Gland Biology and Neoplasia 2008 13 4 381 406
94. Siegel A. B., Zhu A. X., Metabolic syndrome and hepatocellular carcinoma: two growing epidemics with a potential link Cancer 2009 115 24 5651 5661
95. Guzman G., Brunt E. M., Petrovic L. M., Chejfec G., Layden T. J., Cotler S. J., Does nonalcoholic fatty liver disease predispose patients to hepatocellular carcinoma in the absence of cirrhosis? Archives of Pathology and Laboratory Medicine 2008 132 11 1761 1766
96. Zakikhani M., Dowling R., Fantus I. G., Sonenberg N., Pollak M., Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells Cancer Research 2006 66 21 10269 10273 (Pubitemid 44799743)
97. Evans J. M. M., Donnelly L. A., Emslie-Smith A. M., Alessi D. R., Morris A. D., Metformin and reduced risk of cancer in diabetic patients British Medical Journal 2005 330 7503 1304 1305 (Pubitemid 40813563)
98. Bowker S. L., Majumdar S. R., Veugelers P., Johnson J. A., Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin Diabetes Care 2006 29 2 254 258 (Pubitemid 44106500)
99. Zhuang Y., Miskimins W. K., Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1 Journal of Molecular Signaling 2008 3, article 18
100. Donadon V., Balbi M., Ghersetti M., Grazioli S., Perciaccante A., Della Valentina G., Gardenal R., Dal Mas M., Casarin P., Zanette G., Miranda C., Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease World Journal of Gastroenterology 2009 15 20 2506 2511
101. Verlato G., Zoppini G., Bonora E., Muggeo M., Mortality from site-specific malignancies in type 2 diabetic patients from Verona Diabetes Care 2003 26 4 1047 1051 (Pubitemid 36929246)
102. Balkau B., Kahn H. S., Courbon D., Eschwge E., Ducimetire P., Hyperinsulinemia predicts fatal liver cancer but is inversely associated with fatal cancer at some other sites: the Paris Prospective Study Diabetes Care 2001 24 5 843 849 (Pubitemid 33636056)
103. Gaidos J. K. J., Hillner B. E., Sanyal A. J., A decision analysis study of the value of a liver biopsy in nonalcoholic steatohepatitis Liver International 2008 28 5 650 658 (Pubitemid 351541097)
104. Jin X., Ye Y. F., Chen S. H., Yu C. H., Liu J., Li Y. M., MicroRNA expression pattern in different stages of nonalcoholic fatty liver disease Digestive and Liver Disease 2009 41 4 289 297
105. Cheung O., Puri P., Eicken C., Contos M. J., Mirshahi F., Maher J. W., Kellum J. M., Min H., Luketic V. A., Sanyal A. J., Nonalcoholic steatohepatitis is associated with altered hepatic MicroRNA expression Hepatology 2008 48 6 1810 1820
106. Musso G., Gambino R., Cassader M., Emerging molecular targets for the treatment of nonalcoholic fatty liver disease Annual Review of Medicine 2010 61 375 392
107. Krtzfeldt J., Rajewsky N., Braich R., Rajeev K. G., Tuschl T., Manoharan M., Stoffel M., Silencing of microRNAs in vivo with antagomirs Nature 2005 438 7068 685 689
108. Elmén J., Lindow M., Schtz S., Lawrence M., Petri A., Obad S., Lindholm M., Hedtjrn M., Hansen H. F., Berger U., Gullans S., Kearney P., Sarnow P., Straarup E. M., Kauppinen S., LNA-mediated microRNA silencing in non-human primates Nature 2008 452 7189 896 899 (Pubitemid 351550859)
109. Bergeron R., Previs S. F., Cline G. W., Perret P., Russell R. R., Young L. H., Shulman G. I., Effect of 5-aminoimidazole-4-carboxamide-1- -d -ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese zucker rats Diabetes 2001 50 5 1076 1082 (Pubitemid 32374538)
110. Park K. G., Min A. K., Koh E. H., Kim H. S., Kim M. O., Park H. S., Kim Y. D., Yoo T. S., Jang B. K., Hwang J. S., Kim J. B., Choi H. S., Park J. Y., Lee I. K., Lee K. U., Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways Hepatology 2008 48 5 1477 1486
111. Lewis J. R., Mohanty S. R., Nonalcoholic fatty liver disease: a review and update Digestive Diseases and Sciences 2010 55 3 560 578
112. Ding X., Saxena N. K., Lin S., Gupta N., Anania F. A., Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic steatosis in ob/ob mice Hepatology 2006 43 1 173 181 (Pubitemid 43733604)
113. Tushuizen M. E., Bunck M. C., Pouwels P. J., van Waesberghe J. H. T., Diamant M., Heine R. J., Incretin mimetics as a novel therapeutic option for hepatic steatosis Liver International 2006 26 8 1015 1017 (Pubitemid 44323421)