Metabolic Syndrome Traits Increase the Risk of Major Adverse Liver Outcomes in Type 2 Diabetes

Objective: Type 2 diabetes (T2D) increases the risk for major adverse liver outcomes (MALO), including cirrhosis and its complications. Patients with T2D frequently have other traits of the metabolic syndrome (MetS). It remains uncertain whether there is synergistic effect of accumulating MetS traits on future MALO risk.

Research Design and Methods: Patients with T2D without a history of liver disease were identified from national registers in Sweden from 1998 to 2021. MetS traits included hypertension, low HDL level, hypertriglyceridemia, obesity, and albuminuria, in addition to T2D. MALO events were identified based on administrative coding from national registers until Oct 31, 2022. Data were analyzed using Cox regression models.

Results: In total 230,992 patients were identified (median age: 64; 58% male), of which 3,215 (1.39%) developed MALO over a median follow-up of 9.9 years. Compared to patients with one MetS trait (only T2D) at baseline, those with more than one MetS trait had a higher rate of MALO (aHR=2.33, 95% CI=1.53-3.54). The rate of MALO increased progressively with increasing numbers of MetS traits at baseline (aHR=1.28 per added trait, 95% CI=1.23-1.33). During follow-up, patients that acquired additional MetS traits had progressively higher rate of MALO. The MetS trait with the largest association with incident MALO was hypertension (aHR=2.06, 95% CI=1.57-2.71).

Conclusion: Having or acquiring additional traits of the metabolic syndrome increase the rate of progression to major adverse liver outcomes in patients with type 2 diabetes. These results could be used to inform screening initiatives for liver disease.