Objective <p>T2DM (type 2 diabetes mellitus) is a chronic metabolic disease that seriously affects human health. Abnormal expression of microRNAs has been reported to play an important role in disease diagnosis. This study aimed to investigate the predictive value of miR-4454 for T2DM and possible risk factors for comorbidity and complications (CC) of T2DM.</p> Methods <p>Baseline information was collected from a total of 206 subjects including 109 T2DM patients (T2DM group) and 97 healthy individuals (healthy control group), and miR-4454 expression levels were assessed by qRT-PCR. A chi-squared test and a t-test were used to assess the difference in miR-4454 expression of T2DM and healthy subjects. The predictive value of miR-4454 on T2DM was evaluated by receiver operating characteristic (ROC). Potential risk factors for CC of T2DM were predicted by multivariate logistic regression analysis.</p> Results <p>Significant downregulation of miR-4454 was observed in the T2DM group. The predictive value of miR-4454 for T2DM was verified by the ROC curve. MiR-4454 expression in the T2DM group was negatively correlated with fasting blood glucose (FBG), glycated hemoglobin (HbA1c), homeostasis model-insulin resistance index (HOMA-IR), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and positively correlated with the levels of adiponectin (ADI) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Multivariate logistic regression analysis suggested that miR-4454, FBG, HbA1c, HOMA-IR, TC, TG, and LDL-C could be considered risk factors for CC of T2DM.</p> Conclusions <p>The expression level of miR-4454 showed a diagnostic value for T2DM and could serve as a risk factor for the occurrence of CC in T2DM.</p> Clinical trial number <p>Not applicable.</p>