Improvement of nonalcoholic fatty liver disease with carnitine-orotate complex in type 2 diabetes (CORONA): A randomized controlled trial

Diabetes Care

Volumn 38, Issue 7, 2015, Pages 1245-1252

  Bae, Ji Cheol ^a   Lee, Won Young ^b   Yoon, Kun Ho ^c   Park, Joong Yeol ^d   Son, Hyun Sik ^e   Han, Kyung Ah ^f   Lee, Kwan Woo ^g   Woo, Jeong Taek ^h   Ju, Young Cheol ⁱ   Lee, Won Jae ^a   Cho, Yoon Young ^a   Lee, Moon Kyu ^a  

^a Sungkyunkwan University School of Medicine   (South Korea)

^b Sungkyunkwan University School of Medicine   (South Korea)

^c The Catholic University of Korea   (South Korea)

^d University of Ulsan College of Medicine   (South Korea)

^e Uijeongbu St Mary's Hospital   (South Korea)

^f Eulji General Hospital   (South Korea)

^g Ajou University School of Medicine   (South Korea)

^h Kyung Hee University Hospital   (South Korea)

ⁱ Celltrion Pharma   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ANTIDIABETIC AGENT; CARNITINE OROTATE COMPLEX; HEMOGLOBIN A1C; PLACEBO; UNCLASSIFIED DRUG; CARNITINE; DRUG COMBINATION; GLUCOSE BLOOD LEVEL; GLYCOSYLATED HEMOGLOBIN; MICROCAPSULE; VITAMIN;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; COMPUTER ASSISTED TOMOGRAPHY; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; FATTY LIVER; FEMALE; GLYCEMIC CONTROL; HUMAN; LIVER FUNCTION; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; ANTHROPOMETRY; BLOOD; CLINICAL TRIAL; COMPLICATION; DRUG ADMINISTRATION; DRUG COMBINATION; GLUCOSE BLOOD LEVEL; METABOLISM; MICROCAPSULE; MIDDLE AGED; NON-ALCOHOLIC FATTY LIVER DISEASE; SOUTH KOREA;

ALANINE TRANSAMINASE; ANTHROPOMETRY; BLOOD GLUCOSE; CAPSULES; CARNITINE; DIABETES MELLITUS, TYPE 2; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; DRUG COMBINATIONS; FEMALE; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; MALE; MIDDLE AGED; NON-ALCOHOLIC FATTY LIVER DISEASE; REPUBLIC OF KOREA; TOMOGRAPHY, X-RAY COMPUTED; VITAMINS;

EID: 84947560173     PISSN: 01495992     EISSN: 19355548     Source Type: Journal    
DOI: 10.2337/dc14-2852     Document Type: Article

References (40)

1. Lim S. Ectopic fat assessment focusing on cardiometabolic and renal risk. Endocrinol Metab (Seoul) 2014;29:1-4
2. Rector RS, Thyfault JP, Wei Y, Ibdah JA. Non-alcoholic fatty liver disease and the metabolic syndrome: an update. World J Gastroenterol 2008;14:185-192
3. Bae JC, Cho YK, Lee WY, et al. Impact of nonalcoholic fatty liver disease on insulin resistance in relation to HbA1c levels in nondiabetic subjects. Am J Gastroenterol 2010;105:2389-2395
4. Bae JC, Rhee EJ, Lee WY, et al. Combined effect of nonalcoholic fatty liver disease and impaired fasting glucose on the development of type 2 diabetes: a 4-year retrospective longitudinal study. Diabetes Care 2011;34:727-729
5. Chang Y, Jung HS, Yun KE, Cho J, Cho YK, Ryu S. Cohort study of non-alcoholic fatty liver disease, NAFLD fibrosis score, and the risk of incident diabetes in a Korean population. Am J Gastroenterol 2013;108:1861-1868
6. Kim D, Choi SY, Park EH, et al. Nonalcoholic fatty liver disease is associated with coronary artery calcification. Hepatology 2012;56:605-613
7. Shibata M, Kihara Y, Taguchi M, Tashiro M, Otsuki M. Nonalcoholic fatty liver disease is a risk factor for type 2 diabetes in middle-aged Japanese men. Diabetes Care 2007;30:2940-2944
8. Targher G, Bertolini L, Padovani R, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007;30:1212-1218
9. Musso G, Gambino R, Cassader M, Pagano G. A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease. Hepatology 2010;52:79-104
10. Wei Y, Rector RS, Thyfault JP, Ibdah JA. Nonalcoholic fatty liver disease and mitochondrial dysfunction. World J Gastroenterol 2008;14:193-199
11. Murosaki S, Lee TR, Muroyama K, et al. A combination of caffeine, arginine, soy isoflavones, and L-carnitine enhances both lipolysis and fatty acid oxidation in 3T3-L1 and HepG2 cells in vitro and in KK mice in vivo. J Nutr 2007;137:2252-2257
12. Noland RC, Koves TR, Seiler SE, et al. Carnitine insufficiency caused by aging and overnutrition compromises mitochondrial performance and metabolic control. J Biol Chem 2009;284:22840-22852
13. Li JL, Wang QY, Luan HY, Kang ZC, Wang CB. Effects of L-carnitine against oxidative stress in human hepatocytes: involvement of peroxisome proliferator-activated receptor alpha. J Biomed Sci 2012;19:32
14. Jun DW, Cho WK, Jun JH, et al. Prevention of free fatty acid-induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction. Liver Int 2011;31:1315-1324
15. Dobrzyńska I, Szachowicz-Petelska B, Skrzydlewska E, Figaszewski Z. Effect of L-carnitine on liver cell membranes in ethanol-intoxicated rats. Chem Biol Interact 2010;188:44-51
16. Malaguarnera M, Gargante MP, Russo C, et al. L-carnitine supplementation to diet: a new tool in treatment of nonalcoholic steatohepatitis - a randomized and controlled clinical trial. Am J Gastroenterol 2010;105:1338-1345
17. Power RA, Hulver MW, Zhang JY, et al. Carnitine revisited: potential use as adjunctive treatment in diabetes. Diabetologia 2007;50:824-832
18. Ringseis R, Keller J, Eder K. Role of carnitine in the regulation of glucose homeostasis and insulin sensitivity: evidence from in vivo and in vitro studies with carnitine supplementation and carnitine deficiency. Eur J Nutr 2012;51:1-18
19. Wong VW, Vergniol J, Wong GL, et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 2010;51:454-462
20. Kodama Y, Ng CS, Wu TT, et al. Comparison of CT methods for determining the fat content of the liver. AJR Am J Roentgenol 2007;188:1307-1312
21. Limanond P, Raman SS, Lassman C, et al. Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings. Radiology 2004;230:276-280
22. Jacobs JE, Birnbaum BA, Shapiro MA, et al. Diagnostic criteria for fatty infiltration of the liver on contrast-enhanced helical CT. AJR Am J Roentgenol 1998;171:659-664
23. Caldwell SH, Swerdlow RH, Khan EM, et al. Mitochondrial abnormalities in non-alcoholic steatohepatitis. J Hepatol 1999;31:430-434
24. Sobaniec-Lotowska ME, Lebensztejn DM. Ultrastructure of hepatocyte mitochondria in nonalcoholic steatohepatitis in pediatric patients: usefulness of electron microscopy in the diagnosis of the disease. Am J Gastroenterol 2003;98:1664-1665
25. Ibdah JA, Perlegas P, Zhao Y, et al. Mice heterozygous for a defect in mitochondrial trifunctional protein develop hepatic steatosis and insulin resistance. Gastroenterology 2005;128:1381-1390
26. Begriche K, Igoudjil A, Pessayre D, Fromenty B. Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it. Mitochondrion 2006;6:1-28
27. Begriche K, Massart J, Robin MA, Bonnet F, Fromenty B. Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease. Hepatology 2013;58:1497-1507
28. Winter SC, Simon M, Zorn EM, et al. Relative carnitine insufficiency in children with type I diabetes mellitus. Am J Dis Child 1989;143:1337-1339
29. Poorabbas A, Fallah F, Bagdadchi J, et al. Determination of free L-carnitine levels in type II diabetic women with and without complications. Eur J Clin Nutr 2007;61:892-895
30. Victor VM, Apostolova N, Herance R, Hernandez-Mijares A, Rocha M. Oxidative stress and mitochondrial dysfunction in atherosclerosis: mitochondria-targeted antioxidants as potential therapy. Curr Med Chem 2009;16:4654-4667
31. Victor VM, Rocha M, Herance R, Hernandez-Mijares A. Oxidative stress and mitochondrial dysfunction in type 2 diabetes. Curr Pharm Des 2011;17:3947-3958
32. Petersen KF, Befroy D, Dufour S, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 2003;300:1140-1142
33. Hong ES, Kim EK, Kang SM, et al. Effect of carnitine-orotate complex on glucose metabolism and fatty liver: a double-blind, placebo-controlled study. J Gastroenterol Hepatol 2014;29:1449-1457
34. Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 2003;37:1286-1292
35. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 2003;46:3-19
36. Pôrto LC, de Castro CH, Savergnini SS, et al. Improvement of the energy supply and contractile function in normal and ischemic rat hearts by dietary orotic acid. Life Sci 2012;90:476-483
37. Roldan-Valadez E, Favila R, Martínez-López M, Uribe M, Méndez-Sánchez N. Imaging techniques for assessing hepatic fat content in nonalcoholic fatty liver disease. Ann Hepatol 2008;7:212-220
38. Loomba R, Sirlin CB, Ang B, et al. Ezetimibe for the treatment of nonalcoholic steatohepatitis: Assessment by novel magnetic resonance imaging and magnetic resonance elastography in a randomized trial (MOZART trial). Hepatology 2015;61:1239-1250
39. Noureddin M, Lam J, Peterson MR, et al. Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials. Hepatology 2013;58:1930-1940
40. Le TA, Chen J, Changchien C, et al, .; San Diego Integrated NAFLD Research Consortium (SINC). Effect of colesevelam on liver fat quantified by magnetic resonance in nonalcoholic steatohepatitis: a randomized controlled trial. Hepatology 2012;56:922-932