Association of Metabolic Dysfunction-Associated Steatotic Liver Disease Onset Age With Risk of Incident Type 2...

Metabolic dysfunction-associated steatotic liver disease is a known risk factor for type 2 diabetes. However, whether metabolic dysfunction-associated steatotic liver disease onset age modifies type 2 diabetes risk remains poorly understood. We aimed to determine the association of metabolic dysfunction-associated steatotic liver disease onset age and risk of incident type 2 diabetes in a large prospective cohort.

A total of 58,814 metabolic dysfunction-associated steatotic liver disease- and type 2 diabetes-free participants at the first health examination (2006-2007) in the Kailuan Study were included. By December 31, 2015, 29,016 new-onset metabolic dysfunction-associated steatotic liver disease cases were identified. Each metabolic dysfunction-associated steatotic liver disease case was randomly matched to a metabolic dysfunction-associated steatotic liver disease-free control by age (±1 year) and sex. After excluding participants who developed type 2 diabetes within the first 2 years of follow-up, 19,378 metabolic dysfunction-associated steatotic liver disease cases and 19,483 controls were included. All participants were followed for incident type 2 diabetes until December 31, 2020. Cox proportional hazards models estimated hazard ratios and 95% confidence intervals.

During a median follow-up of 11.8 years, 2301 incident type 2 diabetes cases were documented. Compared with non-metabolic dysfunction-associated steatotic liver disease, patients with metabolic dysfunction-associated steatotic liver disease with onset age <40 years had the highest risk of type 2 diabetes (hazard ratio, 6.18; 95% confidence interval, 4.28-8.93), followed by gradually attenuated elevated risks in older onset age groups: 40 to <50 years (hazard ratio, 3.29; 95% confidence interval, 2.70-4.00), 50 to <60 years (hazard ratio, 3.14; 95% confidence interval, 2.69-3.66), 60 to <70 years (hazard ratio, 2.94; 95% confidence interval, 2.39-3.62), and ≥70 years (hazard ratio, 2.17; 95% confidence interval, 1.56-3.01).

Metabolic dysfunction-associated steatotic liver disease onset at any age is associated with increased risk of type 2 diabetes, with earlier onset conferring progressively greater risk. This highlights the importance of preventing, or at least delaying, metabolic dysfunction-associated steatotic liver disease onset, particularly in young adults.