# Transcending risk factors: the implications of redefining diabetes as an immunometabolic disease for infectious disease studies

**Authors:** Xiujun Zhang, Fan Zhang, Wenjian Li

PMC · DOI: 10.3389/fimmu.2026.1794628 · Frontiers in Immunology · 2026-03-13

## TL;DR

This paper argues that diabetes should be redefined as an immunometabolic disease to better understand its impact on infectious diseases and improve treatment strategies.

## Contribution

The paper proposes a new paradigm redefining diabetes as an immunometabolic disorder to explain its effects on immune dysfunction and infection vulnerability.

## Key findings

- Individuals with diabetes have 2- to 4-fold higher hospitalization risk for infections.
- Hyperglycemia and lipotoxicity contribute to chronic inflammation and immune dysfunction in diabetes.
- A comprehensive management approach is needed to restore immune-metabolic homeostasis.

## Abstract

This review methodically argues for a theoretical paradigm shift. The text redefines diabetes as an “immunometabolic disorder” and explores its profound implications. Conventional wisdom has long regarded diabetes as a risk factor for infectious disease comorbidity. Nevertheless, this perspective lacks the depth necessary to elucidate the underlying mechanisms involved. Preliminary clinical research suggests that individuals with diabetes have a 2- to 4-fold higher probability of requiring hospitalization due to infections in comparison with individuals who do not have diabetes. During the pandemic, there was a notable surge in severe illness and mortality rates. These findings suggest limitations in the traditional explanatory framework centered solely on glycemic control. The new paradigm focuses on the co-dysregulation of immunity and metabolism, elucidating how factors such as hyperglycemia and lipotoxicity interact to ultimately drive chronic inflammation and immune dysfunction. This framework elucidates the underlying mechanisms that render individuals with diabetes more vulnerable to various pathogens, expedite disease progression following infection, and manifest diminished therapeutic and vaccine responses. The review further posits that this understanding should inform clinical practice. Rather than prioritizing solely glycemic control, a comprehensive approach to management should encompass metabolic regulation, immune assessment, and infection prevention. Public health policies must explicitly categorize diabetic patients as a priority group for protection. Despite the challenges associated with precise subtyping and the development of targeted interventions, the potential benefits of interdisciplinary efforts and precision medicine strategies are noteworthy. A critical imperative for diabetes management is a transition from a blood glucose control-centric approach to a comprehensive intervention strategy aimed at restoring immune-metabolic homeostasis.

## Linked entities

- **Diseases:** diabetes (MONDO:0005015), infectious disease (MONDO:0005550)

## Full-text entities

- **Diseases:** immunometabolic disease (MESH:D004194), dysregulation (MESH:D021081), infection (MESH:D007239), diabetes (MESH:D003920), immune dysfunction (MESH:D007154), chronic (MESH:D002908), immunometabolic disorder (MESH:D009358), inflammation (MESH:D007249), hyperglycemia (MESH:D006943), infectious disease (MESH:D003141)
- **Chemicals:** blood glucose (MESH:D001786)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13021671/full.md

## References

79 references — full list in the complete paper: https://tomesphere.com/paper/PMC13021671/full.md

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Source: https://tomesphere.com/paper/PMC13021671