# Community-Acquired Pneumonia in Patients With Diabetes: Narrative Review

**Authors:** Yun Xie, Ao Zhang, Ying Wang, Ruilan Wang

PMC · DOI: 10.2196/82215 · 2026-03-10

## TL;DR

People with diabetes are more likely to get severe pneumonia, and this review explores why and how to better treat it.

## Contribution

This paper provides a comprehensive narrative review of CAP in diabetes, highlighting metabolic-immune interactions and novel therapeutic strategies.

## Key findings

- Diabetes increases CAP risk, hospitalization, and mortality due to immune dysfunction and pathogen shifts.
- Moderate glycemic control and targeted therapies improve outcomes in diabetic CAP patients.
- Preventive measures like vaccination reduce CAP admissions by about 45% in this population.

## Abstract

Patients with diabetes carry a 1.5- to 2-fold higher risk of community-acquired pneumonia (CAP) and experience more severe outcomes, yet the mechanisms that integrate metabolic dysregulation, pathogen shifts, and novel cell death pathways remain fragmented.

This study aimed to synthesize current evidence on epidemiology, pathophysiology, causative pathogens, clinical outcomes, and management of CAP in adults with diabetes and to identify research gaps for future trials.

A narrative review (1999 to August 2025) of PubMed, EMBASE, the Cochrane Library, and Web of Science was conducted. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to rate evidence from 81 selected English-language studies (randomized controlled trials, cohorts, and meta-analyses).

Diabetes increases CAP incidence (relative risk 1.73, 95% CI 1.46‐2.04), hospitalization (+30%‐50%), and 30-day mortality (odds ratio 1.67, 95 % CI 1.45-1.92). Key drivers include hyperglycemia-induced immune paralysis, pulmonary microangiopathy, ferroptosis, glycation and methylation changes, and gut-lung dysbiosis that collectively favor multidrug-resistant Gram-negative bacilli (Klebsiella and Pseudomonas) and severe viral and fungal coinfections. Host-targeted therapy with moderate glycemic control (5‐10 mmol/L), continued metformin, and pathogen-directed antibiotics improves survival, whereas single-dose PCV20 and annual influenza vaccination prevents approximately 45% of CAP admissions. Emerging strategies (nanozymes, ferroptosis inhibitors, probiotics, and proteolysis-targeting chimeras) are still preclinical.

CAP in patients with diabetes is a distinct, more severe entity mediated by metabolic-immune crosstalk. Multicenter randomized controlled trials integrating tight glucose monitoring, novel host-directed agents, and microbiome modulation are warranted to translate mechanistic insights into better outcomes.

## Linked entities

- **Chemicals:** metformin (PubChem CID 4091)
- **Diseases:** diabetes (MONDO:0005015)

## Full-text entities

- **Genes:** IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, ZEB1-AS1 (ZEB1 antisense RNA 1) [NCBI Gene 220930], SLC2A4 (solute carrier family 2 member 4) [NCBI Gene 6517] {aka GLUT4}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, HAMP (hepcidin antimicrobial peptide) [NCBI Gene 57817] {aka HEPC, HFE2B, LEAP1, PLTR}, IKBKB (inhibitor of nuclear factor kappa B kinase subunit beta) [NCBI Gene 3551] {aka IKK-2, IKK-beta, IKK2, IKKB, IMD15, IMD15A}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, ACE2 (angiotensin converting enzyme 2) [NCBI Gene 59272] {aka ACEH}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}
- **Diseases:** microvascular damage (MESH:D017566), pneumococcal (MESH:D011008), IPD (MESH:C564352), sputum production (MESH:D007787), gut (MESH:C536735), hypoglycemia (MESH:D007003), infection (MESH:D007239), cardiovascular complications (MESH:D002318), COVID-19 (MESH:D000086382), immune dysfunction (MESH:D007154), cough (MESH:D003371), mucormycosis (MESH:D009091), insulin resistance (MESH:D007333), T2D (MESH:D003924), M. salivarium empyema (MESH:C566367), bacterial infections (MESH:D001424), heart failure (MESH:D006333), invasive pulmonary aspergillosis (MESH:D055744), nephropathy (MESH:D007674), IPA (OMIM:300337), immune dysregulation (OMIM:614878), fungal (MESH:D009181), CAP (MESH:D003147), sepsis (MESH:D018805), post-COVID (MESH:D000094024), Comorbidity (MESH:D004194), injury (MESH:D014947), respiratory infection (MESH:D012141), inflammation (MESH:D007249), Pneumocystis jirovecii (MESH:D011020), critically ill (MESH:D016638), Chronic hyperglycemia (MESH:D006943), Influenza (MESH:D007251), dyslipidemia (MESH:D050171), pulmonary aspergillosis (MESH:D055732), MDR (MESH:D018088), DM (MESH:D003920), CRKP (MESH:D007710), Pulmonary Microangiopathy (MESH:D008171), lung dysbiosis (MESH:D064806), prediabetes (MESH:D011236), lung injury (MESH:D055370), respiratory failure (MESH:D012131), pleural effusion (MESH:D010996), obesity (MESH:D009765), fatigue (MESH:D005221), paralysis (MESH:D010243), Bacterial Pneumonia (MESH:D018410), retinopathy (MESH:D058437), pneumococcal pneumonia (MESH:D011018), K pneumoniae infection (MESH:D011014), Noncommunicable Chronic Diseases (MESH:D000073296), ventilator (MESH:D053717), metabolic (MESH:D008659), ARDS (MESH:D012128), fever (MESH:D005334), hypoglycemic (MESH:C000721848), complement dysfunction (MESH:D000081207), Iron (MESH:D000090463)
- **Chemicals:** BiPt@HMVs (-), baloxavir (MESH:C000628402), amphotericin B. (MESH:D000666), ceftriaxone (MESH:D002443), indomethacin (MESH:D007213), macrolide (MESH:D018942), phenylalanine (MESH:D010649), oseltamivir (MESH:D053139), linezolid (MESH:D000069349), Fluconazole (MESH:D015725), prebiotics (MESH:D056692), beta-lactam (MESH:D047090), glucose (MESH:D005947), 5-azacytidine (MESH:D001374), ferrostatin-1 (MESH:C573944), aminoguanidine (MESH:C004479), azithromycin (MESH:D017963), glycans (MESH:D011134), galactomannan (MESH:C012990), amoxicillin-clavulanate (MESH:D019980), aldosterone (MESH:D000450), tigecycline (MESH:D000078304), remdesivir (MESH:C000606551), methylprednisolone (MESH:D008775), Metformin (MESH:D008687), vancomycin (MESH:D014640), carbapenem (MESH:D015780), iron (MESH:D007501), silver (MESH:D012834), methicillin (MESH:D008712), voriconazole (MESH:D065819), blood glucose (MESH:D001786)
- **Species:** Burkholderia pseudomallei (species) [taxon 28450], Staphylococcus aureus (species) [taxon 1280], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Haemophilus influenzae (species) [taxon 727], Candida [taxon 1535326], Homo sapiens (human, species) [taxon 9606], Enterobacteriaceae (enterobacteria, family) [taxon 543], Pseudomonas (RNA similarity group I, genus) [taxon 286], Legionella pneumophila (species) [taxon 446], gut metagenome (species) [taxon 749906], Aspergillus (genus) [taxon 5052], Escherichia coli (E. coli, species) [taxon 562], Mus musculus (house mouse, species) [taxon 10090], Pseudomonas aeruginosa (species) [taxon 287], Klebsiella pneumoniae (species) [taxon 573], Lacticaseibacillus rhamnosus GG (strain) [taxon 568703], Metamycoplasma salivarium (species) [taxon 2124], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Klebsiella (genus) [taxon 570], Streptococcus pneumoniae (species) [taxon 1313], Enterobacterales (order) [taxon 91347]
- **Cell lines:** BEAS-2B — Homo sapiens (Human), Transformed cell line (CVCL_0168)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12975005/full.md

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Source: https://tomesphere.com/paper/PMC12975005