Abstract 4367950: Intensive lifestyle intervention, MASLD, and cardiovascular outcomes in type 2 diabetes and overweight or obesity: the Look Action for Health in Diabetes (Look AHEAD) trial Liver Ancillary Study

Introduction: Lifestyle modification with weight loss is recommended in type 2 diabetes (T2D) with metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effects of an intensive lifestyle intervention (ILI) targeting weight loss on MASLD in T2D has not been fully characterized. Furthermore, the associations of baseline and longitudinal changes in MASLD with risk of atherosclerotic cardiovascular disease (ASCVD) in T2D is not well-established. Methods: Look AHEAD (Action for Health in Diabetes) trial participants with T2D and overweight or obesity were included. AST, ALT, and GGT were measured at baseline and 1-year follow-up. The probability of MASLD was calculated using the Dallas Steatosis Index (DSI) and the Framingham Steatosis Index (FSI) which were compared with proton magnetic resonance spectroscopy ( 1 H MRS) in a subset of participants with 244 studies. MASLD was defined as hepatic steatosis ≥5.5%. The effect of the ILI versus diabetes support and education (DSE) on measures of MASLD were assessed using least-square means. Adjusted Cox models were created to evaluate the associations of baseline and 1-year longitudinal changes in probability of MASLD with risk of ASCVD (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina). Results: The present study included 3,938 participants with AST, ALT, and GGT data. Among 244 1 H MRS studies, DSI demonstrated fair performance for predicting MASLD (C-statistic: 0.693) and was similar for the FSI at 0.688. The probability of MASLD was estimated in all study participants using the DSI. At 1-year of follow-up, the ILI (versus DSE) reduced the probability of MASLD by 10.3% ( Figure 1A ), decreased the proportion of participants with high probability of MASLD (≥70%) ( Figure 1B ), and reduced AST, ALT, and GGT ( Figure 1C ). In adjusted analyses, higher baseline probability of MASLD was significantly associated with higher risk of ASCVD ( Figure 1D ). Increase in probability of MASLD over 1-year follow-up was significantly associated with higher risk of ASCVD. Conclusions: Among adults with T2D and overweight or obesity, an ILI targeting weight loss reduced the probability of MASLD as well as AST, ALT, and GGT. Higher baseline and longitudinal increases in the probability of MASLD were associated with ASCVD.