Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes

Mariana Lazo, Steven F Solga, Alena Horska, Susanne Bonekamp, Anna Mae Diehl, Frederick L Brancati, Lynne E Wagenknecht, F Xavier Pi-Sunyer, Steven E Kahn, Jeanne M Clark, Fatty Liver Subgroup of the Look AHEAD Research Group, Mariana Lazo, Steven F Solga, Alena Horska, Susanne Bonekamp, Anna Mae Diehl, Frederick L Brancati, Lynne E Wagenknecht, F Xavier Pi-Sunyer, Steven E Kahn, Jeanne M Clark, Fatty Liver Subgroup of the Look AHEAD Research Group

Abstract

Objective: Weight loss through lifestyle changes is recommended for nonalcoholic fatty liver disease (NAFLD). However, its efficacy in patients with type 2 diabetes is unproven.

Research design and methods: Look AHEAD (Action for Health in Diabetes) is a 16-center clinical trial with 5,145 overweight or obese adults with type 2 diabetes, who were randomly assigned to an intensive lifestyle intervention (ILI) to induce a minimum weight loss of 7% or a control group who received diabetes support and education (DSE). In the Fatty Liver Ancillary Study, 96 participants completed proton magnetic resonance spectroscopy to quantify hepatic steatosis and tests to exclude other causes of liver disease at baseline and 12 months. We defined steatosis >5.5% as NAFLD.

Results: Participants were 49% women and 68% white. The mean age was 61 years, mean BMI was 35 kg/m(2), mean steatosis was 8.0%, and mean aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 20.5 and 24.2 units/l, respectively. After 12 months, participants assigned to ILI (n = 46) lost more weight (-8.5 vs. -0.05%; P < 0.01) than those assigned to DSE and had a greater decline in steatosis (-50.8 vs. -22.8%; P = 0.04) and in A1C (-0.7 vs. -0.2%; P = 0.04). There were no significant 12-month changes in AST or ALT levels. At 12 months, 26% of DSE participants and 3% (1 of 31) of ILI participants without NAFLD at baseline developed NAFLD (P < 0.05).

Conclusions: A 12-month intensive lifestyle intervention in patients with type 2 diabetes reduces steatosis and incident NAFLD.

Figures

Figure 1
Figure 1
Median percent change in hepatic steatosis by percent weight change.

References

    1. Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, Day C, Arcaro G: Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 2007;30:1212–1218
    1. Neuschwander-Tetri BA, Caldwell SH: Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37:1202–1219
    1. 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;37:917–923
    1. American Gastroenterological Association Medical Position Statement: nonalcoholic fatty liver disease. Gastroenterology 2002;123:1702–1704
    1. Ryan DH, Espeland MA, Foster GD, Haffner SM, Hubbard VS, Johnson KC, Kahn SE, Knowler WC, Yanovski SZ: Look AHEAD (Action for Health in Diabetes): design and methods for a clinical trial of weight loss for the prevention of cardiovascular disease in type 2 diabetes. Control Clin Trials 2003;24:610–628
    1. Skinner HA, Sheu WJ: Reliability of alcohol use indices. The Lifetime Drinking History and the MAST. J Stud Alcohol 1982;43:1157–1170
    1. Bonekamp S, Ghosh P, Crawford S, Solga SF, Horska A, Brancati FL, Diehl AM, Smith S, Clark JM: Quantitative comparison and evaluation of software packages for assessment of abdominal adipose tissue distribution by magnetic resonance imaging. Int J Obes (Lond) 2008;32:100–111
    1. Wadden TA, West DS, Delahanty L, Jakicic J, Rejeski J, Williamson D, Berkowitz RI, Kelley DE, Tomchee C, Hill JO, Kumanyika S: The Look AHEAD study: a description of the lifestyle intervention and the evidence supporting it. Obesity (Silver Spring) 2006;14:737–752
    1. Pi-Sunyer X, Blackburn G, Brancati FL, Bray GA, Bright R, Clark JM, Curtis JM, Espeland MA, Foreyt JP, Graves K, Haffner SM, Harrison B, Hill JO, Horton ES, Jakicic J, Jeffery RW, Johnson KC, Kahn S, Kelley DE, Kitabchi AE, Knowler WC, Lewis CE, Maschak-Carey BJ, Montgomery B, Nathan DM, Patricio J, Peters A, Redmon JB, Reeves RS, Ryan DH, Safford M, Van Dorsten B, Wadden TA, Wagenknecht L, Wesche-Thobaben J, Wing RR, Yanovski SZ: Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 2007;30:1374–1383
    1. Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P: The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005;129:113–121
    1. Adams LA, Sanderson S, Lindor KD, Angulo P: The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005;42:132–138
    1. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P, Capussotti L, Salizzoni M, Rizzetto M: Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002;123:134–140
    1. Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ: Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology 1999;29:664–669
    1. Cowin GJ, Jonsson JR, Bauer JD, Ash S, Ali A, Osland EJ, Purdie DM, Clouston AD, Powell EE, Galloway GJ: Magnetic resonance imaging and spectroscopy for monitoring liver steatosis. J Magn Reson Imaging 2008;28:937–945
    1. Larson-Meyer DE, Heilbronn LK, Redman LM, Newcomer BR, Frisard MI, Anton S, Smith SR, Alfonso A, Ravussin E: Effect of calorie restriction with or without exercise on insulin sensitivity, β-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care 2006;29:1337–1344
    1. Larson-Meyer DE, Newcomer BR, Heilbronn LK, Volaufova J, Smith SR, Alfonso AJ, Lefevre M, Rood JC, Williamson DA, Ravussin E: Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function. Obesity 2008;16:1355–1362
    1. Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI: Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 2005;54:603–608
    1. Tamura Y, Tanaka Y, Sato F, Choi JB, Watada H, Niwa M, Kinoshita J, Ooka A, Kumashiro N, Igarashi Y, Kyogoku S, Maehara T, Kawasumi M, Hirose T, Kawamori R: Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2005;90:3191–3196
    1. Thamer C, Machann J, Stefan N, Haap M, Schafer S, Brenner S, Kantartzis K, Claussen C, Schick F, Haring H, Fritsche A: High visceral fat mass and high liver fat are associated with resistance to lifestyle intervention. Obesity (Silver Spring) 2007;15:531–538
    1. Thomas EL, Brynes AE, Hamilton G, Patel N, Spong A, Goldin RD, Frost G, Bell JD, Taylor-Robinson SD: Effect of nutritional counselling on hepatic, muscle and adipose tissue fat content and distribution in non-alcoholic fatty liver disease. World J Gastroenterol 2006;12:5813–5819
    1. Tiikkainen M, Bergholm R, Vehkavaara S, Rissanen A, Häkkinen AM, Tamminen M, Teramo K, Yki-Järvinen H: Effects of identical weight loss on body composition and features of insulin resistance in obese women with high and low liver fat content. Diabetes 2003;52:701–707
    1. Viljanen AP, Iozzo P, Borra R, Kankaanpää M, Karmi A, Lautamäki R, Järvisalo M, Parkkola R, Rönnemaa T, Guiducci L, Lehtimäki T, Raitakari OT, Mari A, Nuutila P: Effect of weight loss on liver free fatty acid uptake and hepatic insulin resistance. J Clin Endocrinol Metab 2009;94:50–55
    1. Standards of medical care in diabetes—2010. Diabetes Care 2010;33(Suppl. 1):S11–S61
    1. Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, Fava JL, Wing RR: Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010;51:121–129

Source: PubMed

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