Spatiotemporal burden, risk factors, and genetic causality of non‐alcoholic fatty liver disease and type 2 diabetes mellitus comorbidity in Europe: A multi‐database analysis

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are two core diseases in metabolic syndrome, with a notable rise in their global prevalence, especially in Europe. Despite differences in clinical presentation, both share common pathogenic mechanisms and often occur comorbidly. Understanding the epidemiological patterns of NAFLD and T2DM at different socio-economic levels, as well as the causal relationships between key risk factors, is crucial for developing effective public health intervention strategies. METHODS: This study, based on the Global Burden of Disease (GBD) 2023, integrates the MG randomisation (MR) approach to systematically assess the epidemiological characteristics, spatiotemporal trends, and their relationship with socio-demographic index (SDI) in the European region from 1990 to 2023. Risk factor attribution analysis was conducted using the GBD model, while MR analysis employed the two-sample MR method to explore the causal effects of key metabolic and behavioural factors. RESULTS: The results revealed a significant spatial congruence in the distribution of NAFLD and T2DM across Europe. Joinpoint regression analysis indicated that both diseases followed similar temporal trajectories, characterised by a sustained increase in disease burden within Central and Eastern Europe since 1990. Age-decomposition analysis demonstrated that although the predominant burden remains concentrated among middle-aged and elderly populations, there is a discernible trend towards younger onset for both conditions. Furthermore, the distribution of NAFLD and T2DM across different SDI levels exhibited analogous patterns, revealing an inverted U-shaped association where the highest disease burdens were observed not in the most developed nations, but in high-middle SDI countries currently undergoing rapid nutritional and lifestyle transitions. Risk factor attribution analysis identified high body mass index (BMI), elevated fasting plasma glucose, and smoking as the primary modifiable risk factors for both diseases. MR analysis further confirmed that waist circumference acts as a pivotal shared causal determinant, yielding odds ratios of 2.02 and 3.76, respectively, which were significantly higher than those of other variables. CONCLUSION: This study represents the inaugural integration of GBD 2023 database with MR analysis, systematically elucidating the disease burden trends of NAFLD and T2DM in Europe. The findings precisely characterise the co-morbidity patterns of these two metabolic diseases, highlighting a synergistic effect on disease burden in Central and Eastern Europe that is highly correlated with the region's rapid socio-economic transition. Epidemiological evidence further indicates an accelerating upward trend in the incidence of these diseases among younger populations. Crucially, MR analysis identifies abdominal obesity, quantified by waist circumference, as the dominant causal link between NAFLD and T2DM. Notably, its effect magnitude significantly exceeds that of general BMI or genetic susceptibility. Based on these findings, the study emphasises an urgent need for public health and clinical practice to transition from single-disease management models to integrated metabolic care strategies. Specifically, priority should be given to interventions focused on reducing abdominal fat and implementing early screening among high-risk young populations. This strategy holds promise for effectively curbing the spread of metabolic diseases in Europe and alleviating future public health burdens.