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BACKGROUND: Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels. It is associated with fatty liver disease and elevated liver function tests (LFT) in cross-sectional studies, but data from cohort studies are scarce.

AIM: To investigate the association between insulin and pathological LFT, liver disease, and cirrhosis in a population-based retrospective cohort study.

METHODS: Anthropometric and cardiometabolic factors of 857 men and 1228 women from prospective cohort studies were used. LFT were obtained at two time points 8 years to 24 years after baseline. Liver disease diagnoses were obtained from nationwide registries. The association between insulin levels and the development of elevated LFT or liver disease and cirrhosis was analyzed.

RESULTS: Total follow-up was 54054 person-years for women and 27556 person-years for men. Insulin levels were positively correlated with elevated LFT during follow-up, whereas physical activity and coffee consumption were negatively correlated. Individuals with both insulin levels in the upper tertile and alcohol consumption above MASLD thresholds had an increased risk for both liver disease, adjusted hazard ratio (aHR) of 4.3 (95%CI: 1.6-14.6) and cirrhosis (aHR = 4.8, 95%CI: 1.6-14.6).

CONCLUSION: This population-based study provides evidence that high insulin levels are a risk factor for development of elevated liver enzymes and clinically manifest liver disease. The results support the concept of metabolic dysfunction associated liver disease.