Steatotic Liver Disease Subtypes and Advanced Fibrosis as Independent Predictors of Ischemic Stroke in Type 2 Diabetes Mellitus

Background: Although type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) are associated with an increased risk of ischemic stroke, the extent to which steatotic liver disease (SLD) subtypes and advanced liver fibrosis confer additional risk in individuals with T2DM remains unclear. We aimed to investigate the association of SLD categories and/or advanced liver fibrosis with ischemic stroke risk among patients with T2DM. Methods: A total of 2,220,249 patients with T2DM were classified into five groups: no steatosis, MASLD, MASLD with other combined disease, metabolic dysfunction and alcohol-related steatotic liver disease (MetALD), and alcohol-related liver disease (ALD) with metabolic dysfunction (MD). SLD was defined using a fatty liver index (FLI) of ≥30, and advanced fibrosis was defined by a BARD score of ≥2. Results: Over a median follow-up of 11 years, 135,482 ischemic strokes (6.10%) occurred. Compared with no steatosis, adjusted hazard ratios (aHRs) for stroke were higher in MASLD (aHR, 1.10; 95% confidence interval [CI], 1.08 to 1.11), MASLD with combined disease (aHR, 1.14; 95% CI, 1.12 to 1.17), MetALD (aHR, 1.13; 95% CI, 1.11 to 1.16), and ALD with MD (aHR, 1.32; 95% CI, 1.27 to 1.37). Advanced fibrosis progressively increased stroke risk compared with non-SLD and non-fibrotic SLD. Compared with the FLI <30 group, those with FLI 30-60 and ≥60 showed increased aHRs for stroke. Very heavy drinking was associated with a further increase in risk compared with non-drinking. Conclusion: In patients with T2DM, all SLD categories and advanced liver fibrosis were associated with an increased risk of ischemic stroke. Very heavy alcohol consumption was generally associated with a higher stroke risk across FLI categories.