Spotlight on NAFLD

Several recent studies focused on the intersection of diabetes and nonalcoholic fatty liver disease (NAFLD), also known as metabolic dysfunction-associated steatotic liver disease (MASLD).

First, a cohort study in Korea, published by The BMJ on Feb. 13, categorized more than 7 million patients as having no NAFLD (fatty liver index <30), grade 1 NAFLD (fatty liver index 30 to 60), or grade 2 NAFLD (fatty liver index ≥60). Overall, 6.49% had type 2 diabetes, and they had higher rates of NAFLD than patients without diabetes (34.06% vs. 21.20% for grade 1 and 26.73% vs. 10.02% for grade 2, respectively). The incidence of cardiovascular disease and all-cause death was higher with increasing grade of NAFLD and higher in patients with diabetes than without. Increasing degree of NAFLD was associated with a greater increase in adverse outcomes in diabetes patients. "This study suggests that NAFLD screening and prevention are required to reduce the risk of cardiovascular disease and all cause death in patients with [type 2 diabetes]," the study authors said.

An accompanying editorial noted that the terms NAFLD and nonalcoholic steatohepatitis were updated in June 2023 "to recognise metabolic dysfunction as the underlying cause of both and to remove the term fatty, which is considered stigmatising." The editorial also noted that type 2 diabetes is an important risk factor for MASLD and seems to accelerate the progression of poor liver and cardiovascular outcomes in patients with MASLD. The editorial also reported that the fatty liver index is not typically used in other countries, limiting generalizability, but that the findings may be "especially relevant to people from Asian ethnic groups, since this particular cohort was from South Korea, and may have implications for other high risk groups such as people with severe obesity."

A second study, also from Korea and published by JAMA Internal Medicine on Feb. 12, looked at which diabetes drugs were associated with the best outcomes in patients with NAFLD and type 2 diabetes. This retrospective study compared 80,178 patients who took sodium-glucose cotransporter-2 (SGLT-2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas as second-line therapy. Overall, 4,102 patients had regression of NAFLD. All three of the newer classes were associated with greater likelihood of regression than sulfonylureas, and SGLT-2 inhibitors were associated with a higher likelihood of NAFLD regression than thiazolidinediones (hazard ratio [HR], 1.40; 95% CI, 1.12 to 1.75) and DPP-4 inhibitors (HR, 1.45; 95% CI, 1.30 to 1.62). "The results of this cohort study demonstrated that SGLT2 inhibitors might have potential benefits for patients with both NAFLD and [type 2 diabetes], compared with other [oral antidiabetic] classes," said the study authors, who cautioned that the results were limited by the observational study design.

A third study, published by the Journal of Clinical Endocrinology & Metabolism on Feb. 8, used machine learning to predict risk of MASLD in patients with diabetes. Using data from 2,000 patients, eight parameters were identified as discriminative: age, body mass index, type of diabetes, alanine aminotransferase level, aspartate aminotransferase level, platelet count, hyperuricemia, and treatment with metformin. Data from 1,735 patients showed that 75.08% of patients with MASLD were correctly identified, as were 78.76% without (sensitivity, 0.75; specificity, 0.79). Results from 265 test patients confirmed the model's generalizability (sensitivity, 0.80; specificity, 0.74). "The potential clinical utility of our approach lies in the independent role of MASLD as predictor of [cardiovascular disease], which is distinct and additive to the risks associated with [diabetes] and can help with "tailoring preventive and therapeutic strategies," the study authors said.

Finally, the winter issue of Diabetes Spectrum focused several articles on NAFLD, analyzing the role of insulin resistance in the condition, summarizing relevant guidelines, and offering lifestyle and pharmacological management strategies for clinicians.