Interference of Type 2 Diabetes Mellitus in the Early Diagnosis of Sepsis: Clinical Challenges and Biomarkers

Background/Objectives: Type 2 diabetes mellitus (T2DM) increases the risk of infection and sepsis while modifying host immune responses, clinical presentation, and biomarker performance. This review summarizes the mechanisms through which T2DM interferes with early sepsis recognition and evaluates conventional and emerging biomarkers in this population. Methods: A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science, complemented by Google Scholar. Original studies, systematic reviews, meta-analyses, and international guidelines addressing T2DM, sepsis, immune dysfunction, and sepsis biomarkers were critically analyzed. Results: Chronic hyperglycemia induces immune dysregulation, endothelial dysfunction, and low-grade inflammation, resulting in atypical infection presentations. However, evidence that T2DM reduces the diagnostic performance of clinical screening tools remains limited. Baseline elevations and altered kinetics of C-reactive protein, procalcitonin, interleukin-6, and other inflammatory biomarkers may reduce diagnostic specificity, although diabetes-specific accuracy data are scarce. Lactate retains prognostic value but requires cautious interpretation in diabetic ketoacidosis and metabolic disturbances, which may increase levels independently of sepsis. Emerging biomarkers, including presepsin, pro-adrenomedullin, soluble urokinase plasminogen activator receptor, cell-free DNA, and 16S rRNA, show potential, although evidence in diabetic populations remains limited. Conclusions: T2DM represents a context in sepsis that requires biomarker interpretation. Biomarkers should be interpreted alongside clinical and metabolic findings and according to their intended purpose, distinguishing infection assessment from organ dysfunction and prognostic evaluation. Multimarker strategies integrating clinical, metabolic, and laboratory data may improve early sepsis recognition; however, validation studies involving patients with T2DM are needed.