Effect of a 12-Month Intensive Lifestyle Intervention on Hepatic Steatosis in Adults With Type 2 Diabetes

Abstract

OBJECTIVEWeight 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 METHODSLook 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.RESULTSParticipants were 49% women and 68% white. The mean age was 61 years, mean BMI was 35 kg/m2, 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).CONCLUSIONSA 12-month intensive lifestyle intervention in patients with type 2 diabetes reduces steatosis and incident NAFLD.

Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

“…Two RCTs also showed an improvement in plasma adiponectin [8,12]. Among drugs inducing weight loss, orlistat was safe, well-tolerated with minor adverse gastrointestinal complaints not requiring discontinuation of therapy, but conferred no additional cardio-metabolic or histological benefit over lifestyle intervention alone [7,12].…”

“…Weight loss is safe and may benefit both liver and cardio-metabolic disease in NAFLD: although a ≥5% weight loss improves steatosis and cardio-metabolic variables, a ≥7% weight loss improves also histological disease activity in NASH; however, the latter goal was achieved by <50% individuals even in RCTs adopting intensive multidisciplinary lifestyle interventions, making patient compliance a concern [8,10].…”

“…1); fibrosis was unchanged (not shown). The threshold of 7% weight loss was achieved by <50% of patients, even with intensive multidisciplinary lifestyle intervention [8,10]. Two RCTs suggested no additional NAS improvement with >10% weight loss, but the existence of a lower and an upper threshold weight loss for improving histological disease activity needs further confirmation (Fig.…”

“…Eight RCTs (373 participants, 39% diabetic; six RCTs with a low risk of bias, four RCTs with post-treatment histology) assessed the effect of lifestyle-or drug-induced weight loss in NAFLD [6][7][8][9][10][11][12][13] (ESM Table 1). …”

The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

“…The results from these studies using a variety of interventions, either by diet alone 81,83,84,89,92,93 or in combination with different exercise prescriptions, 82,[85][86][87][88]92,94 have consistently reported a significant reduction in liver fat by an average of $40% (ranging from 20% to 81%). The degree of hepatic fat reduction was proportional to the intensity of the lifestyle intervention and generally required a body weight loss between $5 to 10%.…”