Effects of a low-glycemic, moderately-carbohydrate restricted diet on hepatic lipid content and insulin sensitivity in adolescents with MASLD: protocol of a 6-month family-based, randomized controlled trial

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most prevalent liver disease among children and is closely associated with insulin resistance and increased risk of developing type 2 diabetes (T2D). Early intervention in children with MASLD is essential to prevent progression to advanced liver disease and other metabolic disorders. The goal of this ongoing trial is to determine the effect of a weight-maintaining low glycemic, moderately carbohydrate-restricted diet (CRD) vs. fat-restricted diet (FRD) on changes in hepatic lipid content, insulin sensitivity, and metabolomic profile over a 6-month period in adolescents with MASLD. Eligible participants will be children ages 10-17 with a BMI > 75 th percentile and a clinical diagnosis of MASLD. This randomized control trial (RCT) consists of two 12-week phases: a controlled feeding phase, during which food will be provided to the family, and a free-living phase. The CRD has a macronutrient composition of < 25% CHO: 25% Protein: > 50% fat, while the FRD is composed of 55% CHO: 25% Protein: 20% fat. Primary outcomes include change in hepatic lipid measured by MRI and MRS, and insulin sensitivity measured via euglycemic clamp and metabolomic profiling measured from fasting blood. Diet tolerance, body weight, and compliance were measured weekly by a Registered Dietitian (RD) during the controlled feeding phase, and then monthly in the free-living phase. Changes in study endpoints will be assessed between intervention groups and across study time points, assessing for effects by group, time, and the group-by-time interaction.