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
Open accessAbstract
Both rosiglitazone and metformin increase hepatic insulin sensitivity, but their mechanism of action has not been compared in humans. The objective of this study was to compare the effects of rosiglitazone and metformin treatment on liver fat content, hepatic insulin sensitivity, insulin clearance, and gene expression in adipose tissue and serum adiponectin concentrations in type 2 diabetes. A total of 20 drug-naive patients with type 2 diabetes (age 48 +/- 3 years, fasting plasma glucose 152 +/- 9 mg/dl, BMI 30.6 +/- 0.8 kg/m2) were treated in a double-blind randomized fashion with either 8 mg rosiglitazone or 2 g metformin for 16 weeks. Both drugs similarly decreased HbA1c, insulin, and free fatty acid concentrations. Body weight decreased in the metformin (84 +/- 4 vs. 82 +/- 4 kg, P < 0.05) but not the rosiglitazone group. Liver fat (proton spectroscopy) was decreased with rosiglitazone by 51% (15 +/- 3 vs. 7 +/- 1%, 0 vs. 16 weeks, P = 0.003) but not by metformin (13 +/- 3 to 14 +/- 3%, NS). Rosiglitazone (16 +/- 2 vs. 20 +/- 1 ml.kg(-1).min(-1), P = 0.02) but not metformin increased insulin clearance by 20%. Hepatic insulin sensitivity in the basal state increased similarly in both groups. Insulin-stimulated glucose uptake increased significantly with rosiglitazone but not with metformin. Serum adiponectin concentrations increased by 123% with rosiglitazone but remained unchanged during metformin treatment. The decrease of serum adiponectin concentrations correlated with the decrease in liver fat (r = -0.74, P < 0.001). Rosiglitazone but not metformin significantly increased expression of peroxisome proliferator-activated receptor-gamma, adiponectin, and lipoprotein lipase in adipose tissue. In conclusion, rosiglitazone but not metformin decreases liver fat and increases insulin clearance. The decrease in liver fat by rosiglitazone is associated with an increase in serum adiponectin concentrations. Both agents increase hepatic insulin sensitivity, but only rosiglitazone increases peripheral glucose uptake.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Reductions in hepatic steatosis with both pioglitazone and rosiglitazone ameliorate hepatic insulin resistance.
“Reductions in hepatic steatosis with both pioglitazone and rosig litazone ameliorate hepatic insulin resistance.134,135”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [135]
Metformin does not change liver fat content.
“We have previously shown that metformin does not change liver fat content.35”
From Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes. (2008) · cites this paper as [35]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425 · see citing works
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652 · see citing works
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621 · see citing works
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915 · see citing works
Maeda, N., Takahashi, M., Funahashi, T., Kihara, S., Nishizawa, H., Kishida, K., Nagaretani, H., Matsuda, M., Komuro, R., Ouchi, N., et al. (2001) · Diabetes · doi:10.2337/diabetes.50.9.2094 · Cited by 1,659 · see citing works
Metabolic effects of metformin in non-insulin-dependent diabetes mellitus
Stumvoll, M., Nurjhan, N., Perriello, G., Dailey, G., & Gerich, J. E. (1995) · New England Journal of Medicine · doi:10.1056/nejm199508313330903 · Cited by 1,148 · see citing works
Mechanism by which metformin reduces glucose production in type 2 diabetes.
Hundal, R. S., Krssak, M., Dufour, S., Laurent, D., Lebon, V, Chandramouli, V, Inzucchi, S. E., Schumann, W. C., Petersen, K. F., Landau, B. R., et al. (2000) · Diabetes · doi:10.2337/diabetes.49.12.2063 · Cited by 1,052 · see citing works
Endogenous glucose production is inhibited by the adipose-derived protein Acrp30
Combs, T. P., Berg, A. H., Obici, S., Scherer, P. E., & Rossetti, L. (2001) · Journal of Clinical Investigation · doi:10.1172/jci14120 · Cited by 935 · see citing works
Minimization: A new method of assigning patients to treatment and control groups
Taves, D. R. (1974) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt1974155443 · Cited by 891 · see citing works
Efficacy and Metabolic Effects of Metformin and Troglitazone in Type II Diabetes Mellitus
Inzucchi, S. E., Maggs, D. G., Spollett, G. R., Page, S. L., Rife, F. S., Walton, V., & Shulman, G. I. (1998) · New England Journal of Medicine · doi:10.1056/nejm199803263381303 · Cited by 794 · see citing works
Vidal‐Puig, A., Considine, R. V., Jimenez‐Liñan, M., Werman, A., Pories, W. J., Caro, J. F., & Flier, J. S. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119424 · Cited by 785 · see citing works
Gavrilova, O., Haluzı́k, M., Matsusue, K., Cutson, J. J., Johnson, L. K., Dietz, K. R., Nicol, C. J. B., Vinson, C., Gonzalez, F. J., & Reitman, M. L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300043200 · Cited by 759 · see citing works
Iwaki, M., Matsuda, M., Maeda, N., Funahashi, T., Matsuzawa, Y., Makishima, M., & Shimomura, I. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1655 · Cited by 740 · see citing works
Miyazaki, Y., Mahankali, A., Matsuda, M., Mahankali, S., Hardies, J., Cusi, K., Mandarino, L. J., & DeFronzo, R. A. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.6.8567 · Cited by 726 · see citing works
Auboeuf, D., Rieusset, J., Lluis Fajas, A., Vallier, P., Fréring, V., Riou, J. P., Staels, B., Auwerx, J. H., Laville, M., & Vidal, H. (1997) · Diabetes · doi:10.2337/diab.46.8.1319 · Cited by 699 · see citing works
Hawley, S. A., Gadalla, A. E., Olsen, G. S., & Hardie, D. G. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2420 · Cited by 696 · see citing works
Metformin in non-alcoholic steatohepatitis.
Marchesini, G., Bianchi, G., Tomassetti, S., Zoli, M., & Melchionda, N. (2001) · The Lancet · doi:10.1016/s0140-6736(01)06042-1 · Cited by 682 · see citing works
Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice
Gavrilova, O., Marcus-Samuels, B., Graham, D., Kim, J. K., Shulman, G. I., Castle, A. L., Vinson, C., Eckhaus, M., & Reitman, M. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci7901 · Cited by 676 · see citing works
Metformin reverses fatty liver disease in obese, leptin-deficient mice.
Lin, H. Z., Yang, S. Q., Chuckaree, C., Kuhajda, F., Ronnet, G., & Diehl, A. M. (2000) · Nature Medicine · doi:10.1038/79697 · Cited by 673 · see citing works
Mayerson, A. B., Hundal, R. S., Dufour, S., Lebon, V., Befroy, D., Cline, G. W., Enocksson, S., Inzucchi, S. E., Shulman, G. I., & Petersen, K. F. (2002) · Diabetes · doi:10.2337/diabetes.51.3.797 · Cited by 647 · see citing works
Combs, T. P., Wagner, J. A., Berger, J. P., Doebber, T. W., Wang, W., Zhang, B. B., Tanen, M. R. L., Berg, A. H., O’Rahilly, S., Savage, D. B., et al. (2002) · Endocrinology · doi:10.1210/endo.143.3.8662 · Cited by 565 · see citing works
Cusi, K. J., Consoli, A., & DeFronzo, R. A. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.11.8923861 · Cited by 456 · see citing works
Ryysy, L., Häkkinen, A. M., Goto, T., Vehkavaara, S., Westerbacka, J., Halavaara, J., & Yki-Järvinen, H. (2000) · Diabetes · doi:10.2337/diabetes.49.5.749 · Cited by 431 · see citing works
Self-citationChao, L. C., Marcus‐Samuels, B., Mason, M. M., Moitra, J., Vinson, C., Arioǧlu, E., Gavrilova, O., & Reitman, M. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci11245 · Cited by 356 · see citing works
Bajaj, M., Suraamornkul, S., Pratipanawatr, T., Hardies, L. J., Pratipanawatr, W., Glass, L. C., Cersósimo, E., Miyazaki, Y., & DeFronzo, R. A. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1364 · Cited by 291 · see citing works
Miyazaki, Y., Glass, L. C., Triplitt, C. L., Matsuda, M., Cusi, K. J., Mahankali, A., Mahankali, S., Mandarino, L. J., & DeFronzo, R. A. (2001) · Diabetologia · doi:10.1007/s001250100031 · Cited by 274 · see citing works
Lipid metabolome-wide effects of the PPARγ agonist rosiglitazone
Watkins, S. M., Reifsnyder, P. C., Pan, H.-J., German, J. B., & Leiter, E. H. (2002) · Journal of Lipid Research · doi:10.1194/jlr.m200169-jlr200 · Cited by 274 · see citing works
Kinetics of glucose disposal in whole body and across the forearm in man.
Yki‐Järvinen, H., Young, A. A., Lamkin, C., & Foley, J. E. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113011 · Cited by 265 · see citing works
Modulation of Circulating and Adipose Tissue Adiponectin Levels by Antidiabetic Therapy
Phillips, S. A., Ciaraldi, T. P., Kong, A. P. S., Bandukwala, R., Aroda, V. R., Carter, L., Baxi, S. C., Mudaliar, S. R. D., & Henry, R. R. (2003) · Diabetes · doi:10.2337/diabetes.52.3.667 · Cited by 227 · see citing works
Effect of Rosiglitazone on Insulin Sensitivity and Body Composition in Type 2 Diabetic Patients
Carey, D., Cowin, G., Galloway, G. J., Jones, N. P., Richards, J. C., Biswas, N., & Doddrell, D. M. (2002) · Obesity Research · doi:10.1038/oby.2002.137 · Cited by 210 · see citing works
Sutinen, J., Häkkinen, A., Westerbacka, J., Seppälä‐Lindroos, A., Vehkavaara, S., Halavaara, J. T., Järvinen, A., Ristola, M. A., & Yki‐Järvinen, H. (2003) · Antiviral Therapy · doi:10.1177/135965350300800303 · Cited by 189 · see citing works
Sutinen, J., Häkkinen, A.-M., Westerbacka, J., Seppälä-Lindroos, A., Vehkavaara, S., Halavaara, J., Järvinen, A., Ristola, M., & Yki-Järvinen, H. (2002) · AIDS · doi:10.1097/00002030-200211080-00011 · Cited by 184 · see citing works
Seppala-Lindroos, A. (2002) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.7.3023 · Cited by 168 · see citing works
Self-citationHällsten, K., Virtanen, K. A., Lönnqvist, F., Sipilä, H. T., Oksanen, A., Viljanen, T., Rönnemaa, T., Viikari, J. S. A., Knuuti, J. M., & Nuutila, P. (2002) · Diabetes · doi:10.2337/diabetes.51.12.3479 · Cited by 165 · see citing works
Liver‐Fat Accumulation and Insulin Resistance in Obese Women with Previous Gestational Diabetes
Tiikkainen, M., Tamminen, M., Häkkinen, A., Bergholm, R., Vehkavaara, S., Halavaara, J. T., Teramo, K., Rissanen, A., & Yki‐Järvinen, H. (2002) · Obesity Research · doi:10.1038/oby.2002.118 · Cited by 161 · see citing works
Goto, T., Onuma, T., Takebe, K., & Kral, J. G. (1995) · PubMed · Cited by 145 · see citing works
Rosiglitazone Improves Downstream Insulin Receptor Signaling in Type 2 Diabetic Patients
Miyazaki, Y., He, H., Mandarino, L. J., & DeFronzo, R. A. (2003) · Diabetes · doi:10.2337/diabetes.52.8.1943 · Cited by 136 · see citing works
Reduced hepatic insulin clearance in rats with dietary-induced obesity.
Strömblad, G., & Björntorp, P. (1986) · Metabolism: Clinical and Experimental · doi:10.1016/0026-0495(86)90148-4 · Cited by 126 · see citing works
Edvardsson, U., Bergström, M. F., Alexandersson, M., Bamberg, K., Ljung, B., & Dahllöf, B. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)33479-9 · Cited by 125 · see citing works
Fatty acids in the portal vein of the rat regulate hepatic insulin clearance.
Svedberg, J., Strömblad, G., Wirth, A. G., Smith, U., & Björntorp, P. A. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115534 · Cited by 121 · see citing works
Gustafson, B., Jack, M. M., Cushman, S. W., & Smith, U. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01518-3 · Cited by 120 · see citing works
Neuschwander‐Tetri, B. A., Brunt, E. M., Wehmeier, K. R., Sponseller, C. A., Hampton, K., & Bacon, B. R. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(03)00027-8 · Cited by 119 · see citing works
Kannisto, K., Sutinen, J., Korsheninnikova, E., Fisher, R. M., Ehrenborg, E., Gertow, K., Virkamäki, A., Nyman, T., Vidal, H., Hamsten, A., et al. (2003) · AIDS · doi:10.1097/00002030-200308150-00004 · Cited by 117 · see citing works
Tiikkainen, M., Bergholm, R., Rissanen, A., Aro, A., Salminen, I., Tamminen, M., Teramo, K., & Yki‐Järvinen, H. (2004) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/79.1.22 · Cited by 88 · see citing works
Kim, J. K., Fillmore, J. J., Gavrilova, O., Chao, L. C., Higashimori, T., Choi, H., Kim, H., Yu, C., Chen, Y., Qu, X., et al. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1311 · Cited by 88 · see citing works
Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man
Henriksen, J. H., Tronier, B., & Bülow, J. (1987) · Metabolism · doi:10.1016/0026-0495(87)90044-8 · Cited by 81 · see citing works
Strang, B. D., Bertics, S. J., Grummer, R. R., & Armentano, L. E. (1998) · Journal of Dairy Science · doi:10.3168/jds.s0022-0302(98)75630-9 · Cited by 64 · see citing works
Assay of glucose transport in human fat cells obtained by needle biopsy
Yki-J�rvinen, H., Nikkil�, E. A., Kubo, K., & Foley, J. E. (1986) · Diabetologia · doi:10.1007/bf00452064 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease
(2016) · Journal of Hepatology · doi:10.1016/j.jhep.2015.11.004 · Cited by 4,836 · see citing works
(1998) · PubMed · Cited by 2,737 · see citing works
A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis
Belfort, R., Harrison, S. A., Brown, K., Darland, C., Finch, J., Hardies, J., Balas, B., Gastaldelli, A., Tio, F., Pulcini, J., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa060326 · Cited by 1,827 · see citing works
Yki-Järvinen, H. (2004) · New England Journal of Medicine · doi:10.1056/nejmra041001 · Cited by 1,830 · see citing works
Obesity and the role of adipose tissue in inflammation and metabolism
Greenberg, A. S., & Obin, M. S. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.2.461s · Cited by 1,271 · see citing works
Postic, C., & Girard, J. R. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34275 · Cited by 1,200 · see citing works
Lipid-induced insulin resistance: unravelling the mechanism
Samuel, V. T., Petersen, K. F., & Shulman, G. I. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60408-4 · Cited by 1,189 · see citing works
A position statement on NAFLD/NASH based on the EASL 2009 special conference
Ratziu, V., Bellentani, S., Cortez‐Pinto, H., Day, C., & Marchesini, G. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.04.008 · Cited by 1,058 · see citing works
Targher, G., Bertolini, L., Padovani, R., Rodella, S., Tessari, R., Zenari, L., Day, C. P., & Arcaro, G. (2007) · Diabetes Care · doi:10.2337/dc06-2247 · Cited by 990 · see citing works
Insulin resistance: a metabolic pathway to chronic liver disease
Bugianesi, E., McCullough, A. J., & Marchesini, G. (2005) · Hepatology · doi:10.1002/hep.20920 · Cited by 900 · see citing works
The Role of Insulin Resistance in Nonalcoholic Fatty Liver Disease
Utzschneider, K. M., & Kahn, S. E. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0587 · Cited by 858 · see citing works
Prediction of Non-Alcoholic Fatty Liver Disease and Liver Fat Using Metabolic and Genetic Factors
Kotronen, A., Peltonen, M., Hakkarainen, A., Sevastianova, K., Bergholm, R., Johansson, L., Lundbom, N. M. I., Rissanen, A., Ridderstråle, M., Groop, L., et al. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.06.005 · Cited by 803 · see citing works
Kotronen, A., & Yki‐Järvinen, H. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.147538 · Cited by 793 · see citing works
Mitochondrial dysfunction in Nash: causes, consequences and possible means to prevent it
Begriche, K., Igoudjil, A., Pessayre, D., & Fromenty, B. (2006) · Mitochondrion · doi:10.1016/j.mito.2005.10.004 · Cited by 753 · see citing works
Schwenzer, N. F., Springer, F., Schraml, C., Stefan, N., Machann, J., & Schick, F. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.05.023 · Cited by 751 · see citing works
Kolluru, G. K., Bir, S. C., & Kevil, C. G. (2012) · International Journal of Vascular Medicine · doi:10.1155/2012/918267 · Cited by 728 · see citing works
Bugianesi, E., Gentilcore, E., Manini, R., Natale, S., Vanni, E., Villanova, N., David, E., Rizzetto, M., & Marchesini, G. (2005) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2005.41583.x · Cited by 683 · see citing works
EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease
European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), & European Association for the Study of Obesity (EASO) (2016) · Diabetologia · doi:10.1007/s00125-016-3902-y · Cited by 685 · see citing works
Adiponectin – a key adipokine in the metabolic syndrome
Whitehead, J. P., Richards, A. A., Hickman, I. J., Macdonald, G. A., & Prins, J. B. (2005) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2005.00510.x · Cited by 640 · see citing works
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus
Salpeter, S. R., Greyber, E., Pasternak, G. A., & Salpeter (posthumous), E. E. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002967.pub4 · Cited by 893 · see citing works
Ratziu, V., Giral, P., Jacqueminet, S., Charlotte, F., Hartemann–Heurtier, A., Serfaty, L., Podevin, P., Lacorte, J., Bernhardt, C., Bruckert, E., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.078 · Cited by 625 · see citing works
Musso, G., Cassader, M., Rosina, F., & Gambino, R. (2012) · Diabetologia · doi:10.1007/s00125-011-2446-4 · Cited by 661 · see citing works
A Meta-Analysis of Randomized Trials for the Treatment of Nonalcoholic Fatty Liver Disease
Musso, G., Gambino, R., Cassader, M., & Pagano, G. (2010) · Hepatology · doi:10.1002/hep.23623 · Cited by 561 · see citing works
Systematic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis
Argo, C. K., Northup, P. G., Al‐Osaimi, A. M. S., & Caldwell, S. H. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.03.019 · Cited by 551 · see citing works
Metformin and Its Benefits for Various Diseases
Lv, Z., & Guo, Y. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00191 · Cited by 544 · see citing works
Causes and Metabolic Consequences of Fatty Liver
Stefan, N., Kantartzis, K., & Häring, H. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0009 · Cited by 527 · see citing works
Non-alcoholic fatty liver disease and diabetes
Hazlehurst, J., Woods, C. P., Marjot, T., Cobbold, J., & Tomlinson, J. (2016) · Metabolism · doi:10.1016/j.metabol.2016.01.001 · Cited by 531 · see citing works
Tolman, K. G., Fonseca, V. A., Dalpiaz, A. S., & Tan, M. H. (2007) · Diabetes Care · doi:10.2337/dc06-1539 · Cited by 527 · see citing works
EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease
European Association for the Study of the Liver (EASL), E. A. F. T. S. O. D. (. (2016) · Obesity Facts · doi:10.1159/000443344 · Cited by 522 · see citing works
Sharma, A. M., & Staels, B. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1268 · Cited by 477 · see citing works
Liver Fat in the Metabolic Syndrome
Kotronen, A., Westerbacka, J., Bergholm, R., Pietiläinen, K. H., & Yki‐Järvinen, H. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0482 · Cited by 452 · see citing works
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus
Salpeter, S. R., Greyber, E., Pasternak, G. A., & Salpeter, E. E. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002967.pub3 · Cited by 435 · see citing works
Functions of AMP‐activated protein kinase in adipose tissue
Daval, M., Foufelle, F., & Ferré, P. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.111484 · Cited by 417 · see citing works
The role of leptin/adiponectin ratio in metabolic syndrome and diabetes
López-Jaramillo, P., Gómez-Arbeláez, D., López-López, J., López-López, C., Martínez-Ortega, J., Gómez-Rodríguez, A., & Triana-Cubillos, S. (2014) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2013-0053 · Cited by 405 · see citing works
Mechanisms of Disease: hepatic steatosis in type 2 diabetes—pathogenesis and clinical relevance
Roden, M. (2006) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0190 · Cited by 404 · see citing works
Thiazolidinediones and PPARγ agonists: time for a reassessment
Cariou, B., Charbonnel, B. H., & Staels, B. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.03.001 · Cited by 391 · see citing works
Dietary fat content modifies liver fat in overweight nondiabetic subjects
Westerbacka, J., Lammi, K., Häkkinen, A.-M., Rissanen, A., Salminen, I., Aro, A., & Yki-Järvinen, H. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1983 · Cited by 379 · see citing works
Schindhelm, R. K., Diamant, M., Dekker, J. M., Tushuizen, M. E., Teerlink, T., & Heine, R. J. (2006) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.666 · Cited by 374 · see citing works
Diagnosis and Therapy of Nonalcoholic Steatohepatitis
Torres, D. M., & Harrison, S. A. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.02.077 · Cited by 354 · see citing works
Abnormal Lipid and Glucose Metabolism in Obesity: Implications for Nonalcoholic Fatty Liver Disease
Parekh, S., & Anania, F. A. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.055 · Cited by 340 · see citing works
Kotronen, A., Juurinen, L., Tiikkainen, M., Vehkavaara, S., & Yki–Järvinen, H. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.021 · Cited by 339 · see citing works
Self-citationRisérus, U., Sprecher, D. L., Johnson, T., Olson, E., Hirschberg, S., Liu, A., Fang, Z., Hegde, P. S., Richards, D. B., Sarov-Blat, L., et al. (2007) · Diabetes · doi:10.2337/db07-1318 · Cited by 326 · see citing works
Metformin in patients with non-alcoholic fatty liver disease: A randomized, controlled trial
Haukeland, J. W., Konopski, Z., Eggesbø, H. B., von Volkmann, H. L., Raschpichler, G., Bjøro, K., Haaland, T., Løberg, E. M., & Birkeland, K. (2009) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520902845268 · Cited by 323 · see citing works
Metformin therapy and clinical uses
Scarpello, J. H., & Howlett, H. C. (2008) · Diabetes and Vascular Disease Research · doi:10.3132/dvdr.2008.027 · Cited by 318 · see citing works
Pathogenesis and Prevention of Hepatic Steatosis.
Nassir, F., Rector, R. S., Hammoud, G. M., & Ibdah, J. A. (2015) · PubMed Central · Cited by 321 · see citing works
Diacylglycerol Activation of Protein Kinase Cε and Hepatic Insulin Resistance
Jornayvaz, F. R., & Shulman, G. I. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.005 · Cited by 315 · see citing works
Pathophysiology of nonalcoholic steatohepatitis.
McCullough, A. J. (2006) · PubMed · doi:10.1097/01.mcg.0000168645.86658.22 · Cited by 317 · see citing works
Fatty acid metabolism in adipose tissue, muscle and liver in health and disease
Frayn, K. N., Arner, P., & Yki‐Järvinen, H. (2006) · Essays in Biochemistry · doi:10.1042/bse0420089 · Cited by 316 · see citing works
Janssen, J. A. M. J. L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22157797 · Cited by 296 · see citing works
Gastaldelli, A., Harrison, S. A., Belfort-Aguilar, R., Hardies, L. J., Balas, B., Schenker, S., & Cusi, K. (2009) · Hepatology · doi:10.1002/hep.23116 · Cited by 285 · see citing works
Adiponectin in health and disease
Oh, D. K., Ciaraldi, T. P., & Henry, R. R. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2006.00610.x · Cited by 290 · see citing works
The role of the lipogenic pathway in the development of hepatic steatosis
Postic, C., & Girard, J. R. (2008) · Diabetes & Metabolism · doi:10.1016/s1262-3636(08)74599-3 · Cited by 287 · see citing works
The role of adiponectin in the pathogenesis and treatment of non‐alcoholic fatty liver disease
Pοlyzos, S. A., Kountouras, J., Zavos, C., & Tsiaousi, E. (2009) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2009.01176.x · Cited by 277 · see citing works
Fat in the liver and insulin resistance
Yki‐Järvinen, H. (2005) · Annals of Medicine · doi:10.1080/07853890510037383 · Cited by 267 · see citing works
Role of Insulin Resistance and Lipotoxicity in Non-Alcoholic Steatohepatitis
Cusi, K. J. (2009) · Clinics in Liver Disease · doi:10.1016/j.cld.2009.07.009 · Cited by 263 · see citing works
Current efforts and trends in the treatment of NASH
Ratziu, V., Goodman, Z. D., & Sanyal, A. J. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.041 · Cited by 263 · see citing works
Non-invasive means of measuring hepatic fat content
Mehta, S. R., Thomas, E. L., Bell, J. D., Johnston, D. G., & Taylor-Robinson, S. D. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.3476 · Cited by 256 · see citing works
Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus
Dharmalingam, M., & Yamasandhi, P. (2018) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_585_17 · Cited by 239 · see citing works
Diamanti‐Kandarakis, E., Christakou, C. D., Kandaraki, E., & Economou, F. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0733 · Cited by 246 · see citing works
Schwimmer, J. B., Middleton, M. S., Deutsch, R., & Lavine, J. E. (2005) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2005.02420.x · Cited by 242 · see citing works
Schäffler, A., Schölmerich, J., & Büchler, C. (2005) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep0186 · Cited by 240 · see citing works
Increased Risk of CKD among Type 2 Diabetics with Nonalcoholic Fatty Liver Disease
Targher, G., Chonchol, M., Bertolini, L., Rodella, S., Zenari, L., Lippi, G., Franchini, M., Zoppini, G., & Muggeo, M. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007101155 · Cited by 233 · see citing works
Cuthbertson, D. J., Irwin, A., Gardner, C. J., Daousi, C., Purewal, T., Furlong, N., Goenka, N., Thomas, E. L., Adams, V. L., Pushpakom, S. P., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050117 · Cited by 226 · see citing works
Adiponectin and Cardiovascular Disease
Shibata, R., Ouchi, N., & Murohara, T. (2009) · Circulation Journal · doi:10.1253/circj.cj-09-0057 · Cited by 214 · see citing works
Cariou, B., Hanf, R., Lambert-Porcheron, S., Zaïr, Y., Sauvinet, V., Noël, B., Flet, L., Vidal, H., Staels, B., & Laville, M. (2013) · Diabetes Care · doi:10.2337/dc12-2012 · Cited by 216 · see citing works
Effect of liver fat on insulin clearance
Kotronen, A., Vehkavaara, S., Seppälä-Lindroos, A., Bergholm, R., & Yki-Järvinen, H. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00444.2007 · Cited by 202 · see citing works
Kotronen, A., Juurinen, L., Hakkarainen, A., Westerbacka, J., Cornér, A., Bergholm, R., & Yki-Järvinen, H. (2008) · Diabetes Care · doi:10.2337/dc07-1463 · Cited by 196 · see citing works
Nonalcoholic Steatohepatitis and the Metabolic Syndrome
Neuschwander‐Tetri, B. A. (2005) · The American Journal of the Medical Sciences · doi:10.1097/00000441-200512000-00011 · Cited by 197 · see citing works
Non‐alcoholic fatty liver disease from pathogenesis to management: an update
Musso, G., Gambino, R., & Cassader, M. (2009) · Obesity Reviews · doi:10.1111/j.1467-789x.2009.00657.x · Cited by 197 · see citing works
Pathogenesis of Non-alcoholic Steatohepatitis: Human Data
Edmison, J. M., & McCullough, A. J. (2007) · Clinics in Liver Disease · doi:10.1016/j.cld.2007.02.011 · Cited by 193 · see citing works
Musso, G., Gambino, R., Biroli, G., Carello, M., Fagà, E., Pacini, G., Michieli, F. D., Cassader, M., Durazzo, M., Rizzetto, M., et al. (2005) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2005.00297.x · Cited by 191 · see citing works
The Role of Metformin in the Management of NAFLD
Mazza, A., Fruci, B., Garinis, G. A., Giuliano, S., Malaguarnera, R., & Belfiore, A. (2011) · Experimental Diabetes Research · doi:10.1155/2012/716404 · Cited by 184 · see citing works
Nonalcoholic fatty liver disease in type 2 diabetes mellitus
Cusi, K. J. (2009) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0b013e3283293015 · Cited by 185 · see citing works
Ranganathan, G., Ünal, R., Pokrovskaya, I. D., Yao‐Borengasser, A., Phanavanh, B., Lecka‐Czernik, B., Rasouli, N., & Kern, P. A. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m600248-jlr200 · Cited by 179 · see citing works
Luo, T., Nocon, A., Fry, J., Sherban, A., Rui, X., Jiang, B., Xu, X. J., Han, J., Yan, Y., Yang, Q., et al. (2016) · Diabetes · doi:10.2337/db15-1122 · Cited by 172 · see citing works
Targher, G., Bertolini, L., Rodella, S., Zoppini, G., Scala, L., Zenari, L., & Falezza, G. (2006) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2006.02527.x · Cited by 172 · see citing works
Scheen, A. J., & Paquot, N. (2013) · Diabetes & Metabolism · doi:10.1016/j.diabet.2013.02.006 · Cited by 171 · see citing works
Hepatitis C virus, steatosis and lipid abnormalities: clinical and pathogenic data
Negro, F., & Sanyal, A. J. (2009) · Liver International · doi:10.1111/j.1478-3231.2008.01950.x · Cited by 169 · see citing works
Hutchins, A. M., Brown, B. D., Cunnane, S. C., Domitrovich, S. G., Adams, E. R., & Bobowiec, C. E. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.02.012 · Cited by 166 · see citing works
Feng, W., Gao, C., Bi, Y., Wu, M., Li, P., Shen, S., Chen, W., Yin, T., & Zhu, D. (2017) · Journal of Diabetes · doi:10.1111/1753-0407.12555 · Cited by 165 · see citing works
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus
Salpeter, S. R., Greyber, E., Pasternak, G. A., & Salpeter, E. E. (2006) · The Cochrane Database of Systematic Reviews (Complete Reviews) · doi:10.1002/14651858.cd002967.pub2 · Cited by 163 · see citing works
Viollet, B., Mounier, R., Leclerc, J., Yazigi, A., Foretz, M., & Andréelli, F. (2007) · Diabetes & Metabolism · doi:10.1016/j.diabet.2007.10.004 · Cited by 165 · see citing works
Ectopic fat accumulation and metabolic syndrome
Rasouli, N., Molavi, B., Elbein, S. C., & Kern, P. A. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2006.00590.x · Cited by 164 · see citing works
Reingold, J. S., McGavock, J., Kaka, S., Tillery, T., Victor, R. G., & Szczepaniak, L. S. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00095.2005 · Cited by 154 · see citing works
Wang, Z., Yao, T., Pini, M., Zhou, Z., Fantuzzi, G., & Song, Z. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00249.2009 · Cited by 153 · see citing works
NHG-Standaard Diabetes mellitus type 2
Rutten, G. E. H. M., de Grauw, W. J. C., Nijpels, G., Goudswaard, A. N., Uitewaal, P. J. M., Does, F. E. E. V. D., Heine, R. J., van Ballegooie, E., Verduijn, M., & Bouma, M. (2009) · Bohn Stafleu van Loghum eBooks · doi:10.1007/978-90-313-6614-9_8 · Cited by 150 · see citing works
Peroxisome Proliferator Activated Receptors and Lipoprotein Metabolism
Kersten, S. (2007) · PPAR Research · doi:10.1155/2008/132960 · Cited by 147 · see citing works
Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?
Firneisz, G. (2014) · PubMed Central · doi:10.3748/wjg.v20.i27.9072 · Cited by 147 · see citing works
Barshop, N. J., Sirlin, C. B., Schwimmer, J. B., & Lavine, J. E. (2008) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2008.03703.x · Cited by 145 · see citing works
Juurinen, L., Tiikkainen, M., Häkkinen, A.-M., Hakkarainen, A., & Yki-Järvinen, H. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00133.2006 · Cited by 141 · see citing works
Adiponectin translation is increased by the PPARγ agonists pioglitazone and ω-3 fatty acids
Banga, A., Ünal, R., Tripathi, P., Pokrovskaya, I. D., Owens, R. J., Kern, P. A., & Ranganathan, G. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90892.2008 · Cited by 140 · see citing works
Bajaj, M., Suraamornkul, S., Hardies, L. J., Glass, L. C., Musi, N., & DeFronzo, R. A. (2007) · Diabetologia · doi:10.1007/s00125-007-0698-9 · Cited by 138 · see citing works
The Future of Thiazolidinedione Therapy in the Management of Type 2 Diabetes Mellitus
Yau, H., Rivera, K., Lomonaco, R., & Cusi, K. J. (2013) · Current Diabetes Reports · doi:10.1007/s11892-013-0378-8 · Cited by 139 · see citing works
Insulin resistance and steatosis in humans
Capeau, J. (2008) · Diabetes & Metabolism · doi:10.1016/s1262-3636(08)74600-7 · Cited by 131 · see citing works
Silymarin in non alcoholic fatty liver disease
Cacciapuoti, F. (2013) · World Journal of Hepatology · doi:10.4254/wjh.v5.i3.109 · Cited by 131 · see citing works
Samaha, F. F., Szapary, P. O., Iqbal, N., Williams, M. M., Bloedon, L. T., Kochar, A., Wolfe, M. L., & Rader, D. J. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000200136.56716.30 · Cited by 129 · see citing works
Effect of Vildagliptin on Hepatic Steatosis
Macauley, M., Hollingsworth, K. G., Smith, F. E., Thelwall, P. E., Al-Mrabeh, A. H., Schweizer, A., Foley, J. E., & Taylor, R. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-3794 · Cited by 126 · see citing works
Effect of canagliflozin on liver function tests in patients with type 2 diabetes
Leiter, L. A., Forst, T. M., Polidori, D., Balis, D. A., Xie, J., & Sha, S. (2015) · Diabetes & Metabolism · doi:10.1016/j.diabet.2015.10.003 · Cited by 127 · see citing works
Effects of combined exenatide and pioglitazone therapy on hepatic fat content in type 2 diabetes
Sathyanarayana, P., Jogi, M., Muthupillai, R., Krishnamurthy, R., Samson, S. L., & Bajaj, M. (2011) · Obesity · doi:10.1038/oby.2011.152 · Cited by 124 · see citing works
Liver Fat in the Pathogenesis of Insulin Resistance and Type 2 Diabetes
Yki‐Järvinen, H. (2010) · Digestive Diseases · doi:10.1159/000282087 · Cited by 126 · see citing works
- Authors
- Tiikkainen, M., Häkkinen, A.-M., Korsheninnikova, E., Nyman, T., Mäkimattila, S., & Yki-Järvinen, H.
- Affiliations
- University of Helsinki (FI)
- Department of Medicine, Division of Oncology, University of Helsinki, Helsinki, Finland
- Minerva Foundation (FI)
- Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2004-08-01
- Volume
- 53
- Issue
- 8
- Pages
- 2169-2176
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2107068945
- Cited by
- 524
- References
- 48
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 14 · 2020: 16 · 2019: 6 · 2018: 15 · 2017: 12 · 2016: 18 · 2015: 19 · 2014: 24 · 2013: 26 · 2012: 15
- FWCI
- 34.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Suomen Lääketieteen Säätiö
- Biomedicum Helsinki-säätiö
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- rosiglitazone, metformin, type 2 diabetes, hepatic insulin resistance, hepatic insulin sensitivity, liver fat, insulin clearance, adiponectin, adipose tissue gene expression, PPARγ, lipoprotein lipase, insulin-stimulated glucose uptake, 1H NMR, drug comparison, weight loss, HbA1c
- MeSH terms
- Rosiglitazone, Adipose Tissue, Cholesterol, Diabetes Mellitus, Type 2, Female, Gene Expression Regulation, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Liver, Male, Metformin, Middle Aged, Triglycerides, Thiazolidinediones, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
