Effects of a multifactorial ecosustainable isocaloric diet on liver fat in patients with type 2 diabetes: randomized clinical trial

Giuseppe Della Pepa, Claudia Vetrani, Valentina Brancato, Marilena Vitale, Serena Monti, Giovanni Annuzzi, Gianluca Lombardi, Anna Izzo, Marianna Tommasone, Paola Cipriano, Gennaro Clemente, Peppino Mirabelli, Marcello Mancini, Marco Salvatore, Gabriele Riccardi, Angela Albarosa Rivellese, Lutgarda Bozzetto, Giuseppe Della Pepa, Claudia Vetrani, Valentina Brancato, Marilena Vitale, Serena Monti, Giovanni Annuzzi, Gianluca Lombardi, Anna Izzo, Marianna Tommasone, Paola Cipriano, Gennaro Clemente, Peppino Mirabelli, Marcello Mancini, Marco Salvatore, Gabriele Riccardi, Angela Albarosa Rivellese, Lutgarda Bozzetto

Abstract

Introduction: Treatment options for non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) are still a matter of debate. We compared the effects of a diet including different components versus a proven beneficial diet rich in monounsaturated fatty acids (MUFAs) on liver fat in T2D.

Research design and methods: According to a parallel design, 49 individuals with T2D, overweight/obese, with high waist circumference, 35-75 years-old, in satisfactory blood glucose control with diet or drugs not affecting liver fat content, were randomly assigned to an 8-week isocaloric intervention with a MUFA diet (n=26) or a multifactorial diet rich in fiber, MUFA, n-6 and n-3 polyunsaturated fatty acids, polyphenols, and vitamins D, E, and C (n=23). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS complete data were available for n=21 (MUFA diet) and n=18 (multifactorial diet) participants.

Results: Adherence to dietary interventions was optimal. No significant differences between groups in body weight reduction, plasma glycated hemoglobin, insulin, glucose, lipids and liver enzymes were observed. Liver fat significantly decreased after both the multifactorial diet (9.18%±7.78% vs 5.22%±4.80%, p=0.003) and the MUFA diet (9.47%±8.89% vs 8.07%±8.52%, p=0.027) with a statistically significant difference between changes either in absolute terms (-4.0%±4.5% vs -1.4%±2.7%, p=0.035) or percent (-40%±33% vs -19%±25%, p=0.030).

Conclusions: An isocaloric multifactorial diet including several beneficial dietary components induced a clinically relevant reduction of liver fat in patients with T2D, more pronounced than that induced by simply replacing saturated fat with MUFA. This suggests that the 'optimal diet' for NAFLD treatment in T2D should be based on synergic actions of different dietary components on multiple pathophysiological pathways.

Trial registration number: NCT03380416.

Keywords: dietary intervention; liver fat; type 2 diabetes.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Absolute individual changes (A) and percent changes (B) in liver fat content measured by 1H-MRS after the 8-week intervention with MUFA diet or multifactorial diet. Dotted lines indicate individual values; solid lines denote mean values. Data are expressed as mean±SE. 1H-MRS, magnetic resonance spectroscopy; MUFA, monounsaturated fatty acid.
Figure 2
Figure 2
Spearman correlations between absolute changes after intervention in liver fat and γ-GT (A), fasting plasma glucose (B), and HbA1c (C) levels. ○, MUFA diet; ●, multifactorial diet; γ-GT, gamma-glutamyl transpeptidase; HbA1c, haemoglobin A1c; MUFA, monounsaturated fatty acid.

References

    1. Stefan N, Häring H-U, Cusi K. Non-Alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies. Lancet Diabetes Endocrinol 2019;7:313–24. 10.1016/S2213-8587(18)30154-2
    1. Bril F, Cusi K. Management of nonalcoholic fatty liver disease in patients with type 2 diabetes: a call to action. Diabetes Care 2017;40:419–30. 10.2337/dc16-1787
    1. Promrat K, Kleiner DE, Niemeier HM, et al. . Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010;51:121–9. 10.1002/hep.23276
    1. Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. . Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology 2015;149:367–78. 10.1053/j.gastro.2015.04.005
    1. Della Pepa G, Vetrani C, Lombardi G, et al. . Isocaloric dietary changes and non-alcoholic fatty liver disease in high cardiometabolic risk individuals. Nutrients 2017;9. 10.3390/nu9101065. [Epub ahead of print: 26 Sep 2017].
    1. Westerbacka J, Lammi K, Häkkinen A-M, et al. . Dietary fat content modifies liver fat in overweight nondiabetic subjects. J Clin Endocrinol Metab 2005;90:2804–9. 10.1210/jc.2004-1983
    1. Yki-Järvinen H. Nutritional modulation of non-alcoholic fatty liver disease and insulin resistance. Nutrients 2015;7:9127–38. 10.3390/nu7115454
    1. Meisinger C, Rospleszcz S, Wintermeyer E, et al. . Isocaloric substitution of dietary carbohydrate intake with fat intake and mri-determined total volumes of visceral, subcutaneous and hepatic fat content in middle-aged adults. Nutrients 2019;11. 10.3390/nu11051151. [Epub ahead of print: 23 May 2019].
    1. Bozzetto L, Prinster A, Annuzzi G, et al. . Liver fat is reduced by an isoenergetic MUFA diet in a controlled randomized study in type 2 diabetic patients. Diabetes Care 2012;35:1429–35. 10.2337/dc12-0033
    1. Errazuriz I, Dube S, Slama M, et al. . Randomized controlled trial of a MUFA or Fiber-Rich diet on hepatic fat in prediabetes. J Clin Endocrinol Metab 2017;102:1765–74. 10.1210/jc.2016-3722
    1. Bjermo H, Iggman D, Kullberg J, et al. . Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial. Am J Clin Nutr 2012;95:1003–12. 10.3945/ajcn.111.030114
    1. Schwimmer JB, Ugalde-Nicalo P, Welsh JA, et al. . Effect of a low free sugar diet vs usual diet on nonalcoholic fatty liver disease in adolescent boys: a randomized clinical trial. JAMA 2019;321:256–65. 10.1001/jama.2018.20579
    1. Taskinen M-R, Söderlund S, Bogl LH, et al. . Adverse effects of fructose on cardiometabolic risk factors and hepatic lipid metabolism in subjects with abdominal obesity. J Intern Med 2017;282:187–201. 10.1111/joim.12632
    1. Valtueña S, Pellegrini N, Ardigò D, et al. . Dietary glycemic index and liver steatosis. Am J Clin Nutr 2006;84:136–42. 10.1093/ajcn/84.1.136
    1. Cortez-Pinto H, Jesus L, Barros H, et al. . How different is the dietary pattern in non-alcoholic steatohepatitis patients? Clin Nutr 2006;25:816–23. 10.1016/j.clnu.2006.01.027
    1. Rahman I, Biswas SK, Kirkham PA. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol 2006;72:1439–52. 10.1016/j.bcp.2006.07.004
    1. Annuzzi G, Bozzetto L, Costabile G, et al. . Diets naturally rich in polyphenols improve fasting and postprandial dyslipidemia and reduce oxidative stress: a randomized controlled trial. Am J Clin Nutr 2014;99:463–71. 10.3945/ajcn.113.073445
    1. Bozzetto L, Annuzzi G, Pacini G, et al. . Polyphenol-Rich diets improve glucose metabolism in people at high cardiometabolic risk: a controlled randomised intervention trial. Diabetologia 2015;58:1551–60. 10.1007/s00125-015-3592-x
    1. Zelber-Sagi S, Salomone F, Mlynarsky L. The Mediterranean dietary pattern as the diet of choice for non-alcoholic fatty liver disease: evidence and plausible mechanisms. Liver Int 2017;37:936–49. 10.1111/liv.13435
    1. Ryan MC, Itsiopoulos C, Thodis T, et al. . The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol 2013;59:138–43. 10.1016/j.jhep.2013.02.012
    1. Properzi C, O'Sullivan TA, Sherriff JL, et al. . Ad libitum Mediterranean and low-fat diets both significantly reduce hepatic steatosis: a randomized controlled trial. Hepatology 2018;68:1741–54. 10.1002/hep.30076
    1. Vitale M, Masulli M, Cocozza S, et al. . Sex differences in food choices, adherence to dietary recommendations and plasma lipid profile in type 2 diabetes - The study. Nutr Metab Cardiovasc Dis 2016;26:879–85. 10.1016/j.numecd.2016.04.006
    1. Lohman TM, Roche AF, Martorell R. Anthropometric standardization reference manual. Champaign, IL: Human Kinetics, 1988.
    1. Weis J, Kullberg J, Ahlström H. Multiple breath-hold proton spectroscopy of human liver at 3T: relaxation times and concentrations of glycogen, choline, and lipids. J Magn Reson Imaging 2018;47:410–7. 10.1002/jmri.25734
    1. Mancini M, Salomone Megna A, Ragucci M, et al. . Reproducibility of shear wave elastography (swe) in patients with chronic liver disease. PLoS One 2017;12:e0185391–12. 10.1371/journal.pone.0185391
    1. Ferraioli G, Maiocchi L, Lissandrin R, et al. . Accuracy of the ElastoPq Technique for the assessment of liver fibrosis in patients with chronic hepatitis C: a “real life” single center study. J Gastrointestinal Liver Dis 2016;25:333–5.
    1. Prati D, Taioli E, Zanella A, et al. . Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002;137:1–10. 10.7326/0003-4819-137-1-200207020-00006
    1. Mardinoglu A, Wu H, Bjornson E, et al. . An integrated understanding of the rapid metabolic benefits of a Carbohydrate-Restricted diet on hepatic steatosis in humans. Cell Metab 2018;27:559–71. 10.1016/j.cmet.2018.01.005
    1. Gepner Y, Shelef I, Komy O, et al. . The beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content. J Hepatol 2019;71:379–88. 10.1016/j.jhep.2019.04.013
    1. Most J, Timmers S, Warnke I, et al. . Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial. Am J Clin Nutr 2016;104:215–27. 10.3945/ajcn.115.122937
    1. Bozzetto L, Costabile G, Luongo D, et al. . Reduction in liver fat by dietary MUFA in type 2 diabetes is helped by enhanced hepatic fat oxidation. Diabetologia 2016;59:2697–701. 10.1007/s00125-016-4110-5
    1. Hodson L, Gunn PJ. The regulation of hepatic fatty acid synthesis and partitioning: the effect of nutritional state. Nat Rev Endocrinol 2019;15:689–700. 10.1038/s41574-019-0256-9
    1. Traber MG, Buettner GR, Bruno RS. The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome. Redox Biol 2019;21:101091. 10.1016/j.redox.2018.101091
    1. Ferraioli G, Wong VW-S, Castera L, et al. . Liver ultrasound elastography: an update to the world Federation for ultrasound in medicine and biology guidelines and recommendations. Ultrasound Med Biol 2018;44:2419–40. 10.1016/j.ultrasmedbio.2018.07.008
    1. Vincent MA, Montagnani M, Quon MJ. Molecular and physiologic actions of insulin related to production of nitric oxide in vascular endothelium. Curr Diab Rep 2003;3:279–88. 10.1007/s11892-003-0018-9
    1. Willett W, Rockström J, Loken B, et al. . Food in the Anthropocene: the EAT-Lancet Commission on healthy diets from sustainable food systems. Lancet 2019;393:447–92. 10.1016/S0140-6736(18)31788-4

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