Diabetes Mellitus and Infection Susceptibility: An Immunometabolic Interface

  1. Faissal Al Zeir
  2. May Hamdi
  3. Renad Dawoud
  4. Ahmed Arabi
  5. Kais Nasib Al Shibli
  6. Awab Al-Ani
  7. Alaa Abdelhamid
  8. Hamad Abdel Hadi
  9. Mohammed Seed Ahmed

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Abstract

Diabetes mellitus (DM) is a rapidly growing global health burden and a major driver of infection-related morbidity and mortality. Chronic hyperglycemia disrupts both innate and adaptive immunity through impaired complement activity, dysfunctional dendritic cells and natural killer cells, altered macrophage polarization and efferocytosis, and neutrophil defects including reduced chemotaxis, impaired phagocytosis, and dysregulated NETosis. These immune abnormalities, compounded by endothelial dysfunction and microvascular disease, increase susceptibility to severe and recurrent infections such as urinary tract infections, tuberculosis, pneumonia, skin and soft tissue infections, and invasive fungal diseases. Emerging evidence also supports a bidirectional relationship in which infections may precipitate or aggravate DM via mechanisms including molecular mimicry, β-cell injury, chronic inflammation, and gut microbiota dysbiosis, contributing to insulin resistance and β-cell dysfunction. Recurrent infections and frequent exposure to broad-spectrum antibiotics, together with altered pharmacokinetics, chronic wounds with biofilm formation, and prolonged healthcare exposure, create strong selective pressure for antimicrobial resistance (AMR) in diabetic populations. Using clinical and scientific based evidence, this review explores mechanisms linking DM, infection risk, and AMR, highlighting implications for the diagnosis, therapy, stewardship, and vaccination, as well as outlines key research gaps including improved AMR surveillances stratified by diabetes status and integrated predictive models incorporating glycemic control, host factors, and microbial genomics.

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  1. Version published to 10.3390/microorganisms14112530
  2. PREreview

    This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/21324396.

    Does the introduction explain the objective of the research presented in the preprint? Partly The introduction partly states the study aim but does not explicitly state the specific objectives or research question(s).
    Are the methods well-suited for this research? Somewhat inappropriate The authors do not clearly state the type of the review that was done; even this lacks in the study title. Yet, it is the review that defines the aim/objective(s), scope, and methodology. Therefore, there's limited methodological transparency.
    Are the conclusions supported by the data? Somewhat unsupported The results section is not explicit. Therefore, it is difficult for the readers to know where the conclusions are coming from. Although the authors seem to present rich scientific data on the topic, it is imperative that they provide a clear results section describing the articles that were included and the data of interest therein.
    Are the data presentations, including visualizations, well-suited to represent the data? Somewhat inappropriate or unclear Some figures, such as the first one, are not captioned. The lack of a designated results section makes it difficult for the reader to know which gap the data addresses. For example, the reader cannot is left to assume that table 1 presents part of the review findings, yet it does not indicate the papers from which the presented data was obtained.
    How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Neither clearly nor unclearly The lack of clarity on the type of review that was done and study objectives or research question(s) makes it difficult to judge the quality of the discussion.
    Is the preprint likely to advance academic knowledge? Moderately likely The preprint presents credible medical scientific information that could contribute to the advancement of knowledge. However, it is not well conceptualized, synthesized and presented.
    Would it benefit from language editing? No
    Would you recommend this preprint to others? Yes, but it needs to be improved
    Is it ready for attention from an editor, publisher or broader audience? No, it needs a major revision Please refer to the previous comments.

    Competing interests

    The authors declare that they have no competing interests.

    Use of Artificial Intelligence (AI)

    The authors declare that they did not use generative AI to come up with new ideas for their review.

  3. Version published to 10.20944/preprints202603.2266.v1