Type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) are closely-linked disorders that bidirectionally increase the risk of one another. The prevalence of MASLD in patients with T2DM is more than twice that in the non-diabetic population [1]. The presence of MASLD has reportedly increases the risk of incident T2DM by 1.1- to 2.1-fold [2,3]. In South Korea, the prevalence of MASLD among young adults aged 20 to 39 years has risen rapidly, raising concern about the growing incidence of T2DM in this population [4]. The presence and progression of MASLD, estimated using the fatty liver index (FLI), in young adults is associated with an increased risk of developing T2DM [5]. However, the components of FLI—body mass index (BMI), waist circumference, triglycerides, and γ-glutamyl transferase (GGT)—can be influenced by alcohol consumption. The association between FLI and incident T2DM was investigated in young adults stratified by alcohol consumption status.

Using the Korean National Health Information Database (KNHID), 6,412,270 nondiabetic individuals aged 20 to 39 years, who underwent health examinations between 2009 and 2012, were identified. FLI was calculated and categorized into three groups: <30, 30–60, and ≥60 years. Alcohol consumption was classified as none, mild (<30 g/day) or heavy (≥30 g/day). The operational definition of T2DM diagnosis was consistent with that used in a previous study [6]. The risk of incident T2DM according to FLI and its components was estimated using multivariable Cox proportional hazards models, adjusting for potential confounders including age, sex, smoking, exercise, BMI, GGT, waist circumference, triglycerides, hypertension, dyslipidemia, and fasting glucose. Subgroup analyses based on FLI components were also conducted.

During follow-up, 190,662 participants (3.0%) developed diabetes. The risk of diabetes increased stepwise, with a higher FLI across all alcohol consumption groups (Fig. 1A). Of participants with FLI ≥60, the adjusted hazard ratios for diabetes were 13.66 (95% confidence interval [CI], 13.38 to 13.94) in non-drinkers, 10.41 (95% CI, 10.23 to 10.59) in mild drinkers, and 8.76 (95% CI, 8.37 to 9.16) in heavy drinkers, compared to those with FLI <30. The association between FLI and diabetes risk was stronger in nondrinkers than in drinkers (P for interaction <0.0001). In the subgroup analyses, elevated FLI components were associated with a higher risk of diabetes, regardless of alcohol consumption (Fig. 1B). Among heavy drinkers, participants with triglycerides ≥150 mg/dL or on lipid-lowering therapy had a 1.42-fold higher risk (95% CI, 1.38 to 1.47) compared to those with triglycerides <150 mg/dL. Those with high waist circumference (≥90 cm in men, ≥85 cm in women) had a 1.42-fold higher risk (95% CI, 1.37 to 1.48) compared to those with a normal waist circumference. Participants in the highest GGT quartile had a 2.40-fold higher risk (95% CI, 2.15 to 2.68) compared to those in the lowest quartile. Heavy drinkers with BMI ≥30 kg/m² had a 5.75-fold higher risk (95% CI, 5.37 to 6.17) compared to those in the normal BMI range (18.5 to 23 kg/m²). Taken together, these findings suggest that FLI is a robust predictor of diabetes risk in young adults, independent of alcohol consumption status. Although its predictive performance is the strongest in non-drinkers, FLI remains a useful indicator, even among mild or heavy drinkers.

This study has several important implications. The results highlight the potential of FLI as a non-invasive and useful tool for identifying young individuals at elevated risk of T2DM, even in populations with high rates of alcohol consumption. Identifying at-risk young adults is particularly important, as early onset T2DM is associated with more aggressive disease progression, earlier onset of complications, and increased lifetime healthcare burden compared to later-onset diabetes [6]. The observation of a stronger association between nondrinkers and drinkers may suggest a relative attenuation of predictive accuracy in individuals with alcohol exposure. This could be due to alcohol-related modulation of GGT or lipid metabolism, which may partially mask the underlying contribution of fatty liver to the development of diabetes. Nevertheless, the persistence of a robust association, even in heavy drinkers, indicates that the pathophysiological link between fatty liver and diabetes remains strong. Mechanistically, MASLD contributes to insulin resistance, systemic inflammation, and β-cell dysfunction [7]. Alcohol-related metabolic changes may affect these pathways.

From a public health perspective, these results emphasize the need for early lifestyle interventions in young adults with a high FLI, regardless of their drinking habits. Considering the increasing prevalence of MASLD and T2DM among young adults in South Korea and globally, adopting proactive approaches is essential to mitigate future cardiovascular and renal complications. The large number of participants is a strength of this study. A sample size of over six million young adults offers strong statistical power and generalizability. The longitudinal design with comprehensive adjustment for confounders enhanced the robustness of the observed associations.

Nonetheless, limitations of this study should be acknowledged. Alcohol consumption was self-reported, raising the possibility of underestimation or misclassification of intake. Residual confounding factors cannot be entirely excluded, despite adjustment for multiple metabolic variables. Patients with alcoholic liver disease (ALD) or metabolic dysfunction-associated alcoholic liver disease (MetALD) were not differentiated in the study. In this study, heavy alcohol consumption was defined as ≥30 g/day. In prior research, ALD has been defined as alcohol consumption ≥60 g/day and MetALD as FLI ≥60 with alcohol consumption ≥60 g/day [8]. Accordingly, by our definition, some patients with MetALD may have been included in the heavy drinker group with FLI ≥60. Nevertheless, the findings support the use of FLI as a valuable tool for identifying individuals at high risk of diabetes, regardless of alcohol consumption status.

In conclusion, FLI is a robust predictor of incident T2DM in young adults, independent of alcohol consumption status. These findings support the use of FLI in large-scale screening and prevention programs aimed at screening for early onset diabetes. Incorporating FLI into routine health assessments could facilitate timely identification and intervention for high-risk individuals, ultimately reducing the burden of diabetes and its complications.