The Diabetes-Viral Respiratory Syndemic: Pathophysiological Insights and Precision Management: A Scoping Review.

Background/

Objectives

Viral respiratory tract infections (VRTIs) in patients with diabetes mellitus (DM) are characterized by a severity gap rather than an infection gap. This review synthesizes evidence from the 2023-2026 respiratory seasons to provide a post-pandemic framework for managing the synergistic metabolic and viral threats in this population. Materials and

Methods

A scoping review of literature from PubMed, Scopus, and Embase (2023-2026) was conducted, focusing on clinical outcomes and mechanistic interactions between DM and emerging respiratory pathogens.

Results

Recent data identify human Metapneumovirus (hMPV) and adenovirus as significant threats to diabetic hosts, with mortality risks equivalent to seasonal influenza (HR 1.00 for hMPV vs. influenza). The two-hit model combines a baseline of innate immune paralysis, characterized by impaired neutrophil chemo-taxis and mechanical SP-D dysfunction, with a cellular signaling environment primed for cytokine overreaction by epigenetic metabolic memory. The stress hyperglycemia ratio (SHR) has emerged as a promising predictor of mortality compared to absolute glucose or HbA1c, with a proposed threshold of ≥1.14 identifying patients at 3.5-fold increased risk for mechanical ventilation. Precision management should consider the prudent suspension of SGLT2 inhibitors to mitigate euglycemic DKA risks and considering the early use of GLP-1 receptor agonists for their hypothesized pulmonary anti-inflammatory properties.

Conclusions

Closing the mortality gap may require a shift from generic viral care to a precision model that treats metabolic susceptibility with high clinical priority alongside the treatment of the viral pathogen.