The physical activity intervention relied heavily on unsupervised exercise, because

that has been more effective for long-term adherence than supervised exercise.25 The program focused on moderate-intensity activities, with particular emphasis on walking. All participants were given pedometers and encouraged to gradually Selleck AZD6244 increase their walking until reaching 10,000 steps per day. Other activities such as bicycling, aerobic dance, and strength training were also encouraged. Participants were instructed to gradually progress to a goal of 200 minutes per week of moderate-intensity physical activity (achieving this goal by the end of the first 6 months). The 200-minute goal is selected in preference to a 150-minute or 175-minute goal because greater amounts of activity have been associated with better long-term weight loss results.26 To improve adherence to exercise, participants were encouraged to accumulate exercise through multiple selleck inhibitor short bouts of exercise (at least 10 minutes in duration). Behavioral strategies were used to produce and maintain changes in diet and activity. All participants were encouraged to self-monitor their eating and exercise (recording all foods eaten and calories and fat grams in their foods and minutes of activity) daily throughout the entire weight loss program. Self-monitoring records were reviewed weekly by the therapist in collaboration with the participant to identify

areas of progress and areas in which further change would be advantageous. Other key behavioral strategies such as stimulus control techniques, problem solving,27 and relapse prevention28 were taught in the weekly group sessions. Participants set individual behavioral goals with the case manager and brainstormed solutions heptaminol to any barriers to achieving the weight loss, activity, or dietary goals. Clinical trials suggest that insulin-sensitizing agents (thiazolidinediones and metformin) may have biochemical and histological effects on NASH. To avoid the potential confounding effects from these medications, participants

were not allowed to start on any of these medications during the entire study period. Participants were allowed to start a new medication for management of hyperglycemia if medically necessary. Sulfonylureas, meglitinides, and insulin were available options. Participants who were already taking thiazolidinediones or metformin had to be on a stable regimen for at least 6 months before study enrollment and initial liver biopsy. The dose of these medications had to remain stable during the study. The rationale was that patients who have been on these medications and continue to have active NASH should be allowed to participate in the study to maximize generalizability. These medications should have minimal or no effect on hepatic histology during the study period. Exercise and reduced caloric consumption can produce hypoglycemia in patients with type 2 diabetes who are on insulin or sulfonylureas.