Impact of insulin resistance on mild cognitive impairment in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease

Abstract Aims Insulin resistance (IR) is a pivotal factor in the pathogenesis of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Nevertheless, the impact of IR on cognitive dysfunction in T2DM patients with NAFLD remains inadequately understood. We aim to investigate the effect of IR on mild cognitive impairment (MCI) in T2DM individuals with NAFLD. Materials and methods 143 T2DM individuals were categorized into Non-MCI and MCI groups, as well as Non-NAFLD and NAFLD groups. Clinical parameters and cognitive preference test outcomes were compared. Correlation and regression analyses were executed to explore the interconnections between IR and cognitive details across all T2DM patients, as well as within the subgroup of individuals with NAFLD. Results In comparison to the Non-MCI group, the MCI group displayed elevated HOMA-IR levels. Similarly, the NAFLD group exhibited higher HOMA-IR levels compared to the Non-NAFLD group. Additionally, a higher prevalence of MCI was observed in the NAFLD group as opposed to the Non-NAFLD group. Notably, HOMA-IR levels were correlated with Verbal Fluency Test (VFT) and Trail Making Test-B (TMTB) scores, both related to executive functions. Elevated HOMA-IR emerged as a risk factor for MCI in the all patients. Intriguingly, increased HOMA-IR not only correlated with TMTB scores but also demonstrated an influence on TMTA scores, reflecting information processing speed function in patients with NAFLD. Conclusion IR emerges as a contributory factor to cognitive dysfunction in T2DM patients. Furthermore, it appears to underlie impaired executive function and information processing speed function in T2DM individuals with NAFLD.