Dapagliflozin significantly reduced liver fat accumulation associated with a decrease in abdominal subcutaneous fat in patients with inadequately controlled type 2 diabetes mellitus

Diabetes Research and Clinical Practice

Volumn 142, Issue , 2018, Pages 254-263

  Kurinami, Noboru ^a   Sugiyama, Seigo ^a   Yoshida, Akira ^a   Hieshima, Kunio ^a   Miyamoto, Fumio ^a   Kajiwara, Keizo ^a   Jinnouch, Katsunori ^a,b   Jinnouchi, Tomio ^a   Jinnouchi, Hideaki ^a,b  

^a Jinnouchi Hospital   (Japan)

^b KUMAMOTO UNIVERSITY HOSPITAL   (Japan)

Author keywords

Abdominal fat; Computed tomography; Diabetes mellitus; Ectopic fat; Liver fat accumulation; Liver to spleen attenuation ratio; Sodium glucose cotransporter 2 inhibitors

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; C PEPTIDE; DAPAGLIFLOZIN; FATTY ACID; GAMMA GLUTAMYLTRANSFERASE; HEMOGLOBIN A1C; 2-(3-(4-ETHOXYBENZYL)-4-CHLOROPHENYL)-6-HYDROXYMETHYLTETRAHYDRO-2H-PYRAN-3,4,5-TRIOL; ANTIDIABETIC AGENT; BENZHYDRYL DERIVATIVE; GLUCOSIDE;

ABDOMINAL SUBCUTANEOUS FAT; ADULT; ARTICLE; BODY COMPOSITION; BODY WEIGHT CHANGE; COMPUTER ASSISTED TOMOGRAPHY; DRUG EFFECT; FAT MASS; FATTY LIVER; FEMALE; HUMAN; INTRA-ABDOMINAL FAT; JAPANESE (PEOPLE); LIPID STORAGE; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; NON INSULIN DEPENDENT DIABETES MELLITUS; PLATELET COUNT; PROSPECTIVE STUDY; TREATMENT OUTCOME; BLOOD; GLUCOSE BLOOD LEVEL; METABOLISM;

BENZHYDRYL COMPOUNDS; BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; FATTY LIVER; FEMALE; GLUCOSIDES; HUMANS; HYPOGLYCEMIC AGENTS; MALE; MIDDLE AGED; PROSPECTIVE STUDIES; SUBCUTANEOUS FAT, ABDOMINAL; TREATMENT OUTCOME;

EID: 85048597520     PISSN: 01688227     EISSN: 18728227     Source Type: Journal    
DOI: 10.1016/j.diabres.2018.05.017     Document Type: Article

References (41)

1. Vernon, G., Baranova, A., Younossi, Z.M., Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34 (2011), 274–285.
2. Suzuki, K., Kirikoshi, H., Yoneda, M., Mawatari, H., Fujita, K., Nozaki, Y., et al. Measurement of spleen volume is useful for distinguishing between simple steatosis and early-stage non-alcoholic steatohepatitis. Hepatol Res 40:7 (2010), 693–700.
3. Sakurai, M., Takamura, T., Ota, T., Ando, H., Akahori, H., Kaji, K., et al. Liver steatosis, but not fibrosis, is associated with insulin resistance in nonalcoholic fatty liver disease. J Gastroenterol 42 (2007), 312–317.
4. Kurinami, N., Sugiyama, S., Yoshida, A., Hieshima, K., Miyamoto, F., Kajiwara, K., et al. Correlation of body muscle/fat ratio with insulin sensitivity using hyperinsulinemic-euglycemic clamp in treatment-naïve type 2 diabetes mellitus. Diabetes Res Clin Pract 120 (2016), 65–72.
5. Kurinami, N., Sugiyama, S., Ayami, M., Yoshida, A., Hieshima, K., Miyamoto, F., et al. Ratio of muscle mass to fat mass assessed by bioelectrical impedance analysis is significantly correlated with liver fat accumulation in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract, 2018, 10.1016/j.diabres.2018.02.009.
6. Leite, N.C., Salles, G.F., Araujo, A.L., Villela-Nogueira, C.A., Cardoso, C.R., Prevalence and associated factors of non-alcoholic fatty liver disease in patients with type-2 diabetes mellitus. Liver Int 29:1 (2009), 113–119.
7. Reid, A.E., Nonalcoholic steatohepatitis. Gastoroenterology 121:3 (2001), 710–723.
8. Bril, F., Cusi, K., Management of nonalcoholic fatty liver disease in patients with type 2 diabetes: a call to action. Diabetes Care 40:3 (2017), 419–430.
9. Kurinami, N., Sugiyama, S., Nishimura, H., et al. Clinical factors associated with initial decrease in body-fat percentage induced by add-on sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes mellitus. Clin Drug Invest 38:1 (2018), 19–27.
10. Seko, Y., Sumida, Y., Tanaka, S., Mori, K., Taketani, H., Ishiba, H., et al. Effect of sodium glucose cotransporter 2 inhibitor on liver function tests in Japanese patients with non-alcoholic fatty liver disease and type 2 diabetes mellitus. Hepatol Res 47:10 (2017), 1072–1078.
11. Armstrong, M.J., Gaunt, P., Aithal, G.P., Barton, D., Hull, D., Parker, R., et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study. Lancet 387:10019 (2016), 679–690.
12. Ito, D., Shimizu, S., Inoue, K., Saito, D., Yanagisawa, M., Inukai, K., et al. Comparison of ipragliflozin and pioglitazone effects on nonalcoholic fatty liver disease in patients with type 2 diabetes: a randomized, 24-week, open-label, active-controlled trial. Diabetes Care 40:10 (2017), 1364–1372.
13. Shibuya, T., Fushimi, N., Kawai, M., Yoshida, Y., Hachiya, H., Ito, S., et al. Luseogliflozin improves liver fat deposition compared with metformin in type 2 diabetes patients with non-alcoholic fatty liver disease: a prospective randomized controlled pilot study. Diabetes Obes Metab 20:2 (2018), 438–442.
14. Sugiyama, S., Jinnouchi, H., Kurinami, N., Hieshima, K., Yoshida, A., Jinnouchi, K., et al. Dapagliflozin reduces fat mass without affecting muscle mass in type 2 diabetes. J Atheroscler Thromb, 2017, 10.5551/jat.40873.
15. Kan, H., Kimura, Y., Hyogo, H., Fukuhara, T., Fujino, H., Naeshiro, N., et al. Non-invasive assessment of liver steatosis in non-alcoholic fatty liver disease. Hepatol Res 44 (2014), E420–E427.
16. Cha, K., Chertow, G.M., Gonzalez, J., Lazarus, J.M., Wilmore, D.W., Multifrequency bioelectrical impedance estimates the distribution of body water. J Appl Physiol 79:4 (1995), 1316–1319.
17. Cha, K., Shin, S., Shon, C., Choi, S., Wilmore, D.W., Evaluation of segmental bioelectrical impedance analysis (SIBA) for measuring muscle distribution. J ICHPER SD-ASIA, 1997, 11–14.
18. Iwasaki, M., Takada, Y., Hayashi, M., Minamiguchi, S., Haga, H., Maetani, Y., et al. Noninvasive evaluation of graft steatosis in living donor liver transplantation. Transplantation 78:10 (2004), 1501–1505.
19. Sanyal, A.J., Chalasani, N., Kowdley, K.V., McCullough, A., Diehl, A.M., Bass, N.M., et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 362 (2010), 1675–1685.
20. Liu, J., Wang, G., Jia, Y., Xu, Y., GLP-1 receptor agonists: effects on the progression of non-alcoholic fatty liver disease. Diabetes Metab Res Rev 31:4 (2015 May), 329–335.
21. Giorgino, F., Laviola, L., Eriksson, J.W., Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies. Acta Physiol Scand 183 (2005), 13–32.
22. Park, B.J., Kim, Y.J., Kim, D.H., Kim, W., Jung, Y.J., Yoon, J.H., et al. Visceral adipose tissue area is an independent risk factor for hepatic steatosis. J Gastroenterol Hepatol 23:6 (2008), 900–907.
23. Eguchi, Y., Eguchi, T., Mizuta, T., Ide, Y., Yasutake, T., Iwakiri, R., et al. Visceral fat accumulation and insulin resistance are important factors in nonalcoholic fatty liver disease. J Gastroenterol 41:5 (2006), 462–469.
24. Harrison, S.A., Kadakia, S., Lang, K.A., Schenker, S., Nonalcoholic steatohepatitis: what we know in the new millennium. Am J Gastroenterol 97:11 (2002), 2714–2724.
25. Donnelly, K.L., Smith, C.I., Schwarzenberg, S.J., Jessurun, J., Boldt, M.D., Parks, E.J., Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115:5 (2005), 1343–1351.
26. Williams, B., Insulin resistance: the shape of things to come. Lancet 344 (1994), 521–524.
27. Shi, H., Kokoeva, M.V., Inouye, K., Tzameli, I., Yin, H., Flier, J.S., TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116:11 (2006), 3015–3025.
28. Poggi, M., Bastelica, D., Gual, P., Iglesias, M.A., Gremeaux, T., Knauf, C., et al. C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet. Diabetologia 50:6 (2007), 1267–1276.
29. Suganami, T., Mieda, T., Itoh, M., Shimoda, Y., Kamei, Y., Ogawa, Y., Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation. Biochem Biophys Res Commun 354:1 (2007), 45–49.
30. Akuta, N., Watanabe, C., Kawamura, Y., Arase, Y., Saitoh, S., Fujiyama, S., et al. Effects of a sodium–glucose cotransporter 2 inhibitor in nonalcoholic fatty liver disease complicated by diabetes mellitus: preliminary prospective study based on serial liver biopsies. Hepatol Commun 1:1 (2017), 46–52.
31. Dulai, P.S., Singh, S., Patel, J., Soni, M., Prokop, L.J., Younossi, Z., et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology 65:5 (2017), 1557–1565.
32. Portillo-Sanchez, P., Cusi, K., Treatment of NAFLD in patients with type 2 diabetes mellitus. Clin Diabetes Endocrinol, 12(2), 2016, 9.
33. Komiya, C., Tsuchiya, K., Shiba, K., Miyachi, Y., Furuke, S., Shimazu, N., et al. Ipragliflozin improves hepatic steatosis in obese mice and liver dysfunction in type 2 diabetic patients irrespective of body weight reduction. PLoS One, 11(3), 2016, e0151511.
34. Honda, Y., Imajo, K., Kato, T., Kessoku, T., Ogawa, Y., Tomeno, W., et al. The selective SGLT2 inhibitor ipragliflozin has a therapeutic effect on nonalcoholic steatohepatitis in mice. PLoS One, 11(1), 2016, e0146337.
35. Nakano, S., Katsuno, K., Isaji, M., Nagasawa, T., Buehrer, B., Walker, S., et al. Remogliflozin etabonate improves fatty liver disease in diet-induced obese male mice. J Clin Exp Hepatol 5:3 (2015), 190–198.
36. Jojima, T., Tomotsune, T., Iijima, T., Akimoto, K., Suzuki, K., Aso, Y., Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes. Diabetol Metab Syndr, 8, 2016, 45.
37. Inokuchi, T., Watanabe, K., Kameyama, H., Orita, M., Altered basal C-peptide/insulin molar ratios in obese patients with fatty liver. Jpn J Med 27:3 (1988), 272–276.
38. Bril, F., Lomonaco, R., Orsak, B., Ortiz-Lopez, C., Webb, A., Tio, F., et al. Relationship between disease severity, hyperinsulinemia, and impaired insulin clearance in patients with nonalcoholic steatohepatitis. Hepatology 59:6 (2014), 2178–2187.
39. Ekholm, E., Hansen, L., Johnsson, E., Iqbal, N., Carlsson, B., Chen, H., et al. Combined treatment with saxagliptin plus dapafliflozin reduces insulin levels by increased insulin clearance and improves β-cell function. Endo Pract 23:3 (2017), 258–265.
40. Suzuki, M., Takeda, M., Kito, A., Fukazawa, M., Yata, T., Yamamoto, M., et al. Tofogliflozin, a sodium/glucose cotransporter 2 inhibitor, attenuates body weight gain and fat accumulation in diabetic and obese animal models. Nutr Diabetes, 4, 2014, e125.
41. Obara, K., Shirakami, Y., Maruta, A., Ideta, T., Miyazaki, T., Kochi, T., et al. Preventive effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on diethylnitrosamine-induced liver tumorigenesis in obese and diabetic mice. Oncotarget 8:35 (2017), 58353–58363.