The overlooked triad: interrelationship between diabetes mellitus, diabetic foot, and acute diarrhoea. A systematic review of clinical and pathophysiological correlates.

Abstract

Background:

Diabetes mellitus (DM) and its complications, particularly diabetic foot disease (DFD), substantially increase morbidity through vascular, immune, and microbiome dysfunction. Acute diarrhoeal illnesses, including Clostridioides difficile infection (CDI), antibiotic-associated diarrhoea (AAD), and cholera, can further destabilize metabolic and infectious trajectories in diabetic patients. Despite this overlap, integrated evidence on their interrelationship remains limited.

Objective:

To systematically evaluate current evidence on (1) the role of diabetes as a risk factor for CDI and other diarrhoeal diseases; (2) the impact of antibiotic exposure and metabolic instability on outcomes; (3) the potential protective effect of metformin therapy; and (4) the broader clinical implications for diabetic foot and inpatient management.

Methods:

Following PRISMA-2020 guidelines, open-access observational studies were identified in PubMed, DOAJ, PMC, Google Scholar, and OpenAIRE up to July 2025. Eligible studies included adults (≥18 years) with DM experiencing diarrhoeal illness. Outcomes analyzed were CDI incidence or recurrence, AAD occurrence, in-hospital mortality, and length of stay (LOS). Quality was assessed using the Newcastle–Ottawa Scale (NOS).

Results:

Six studies (2011–2024) met the inclusion criteria. Diabetes independently increased CDI risk and recurrence (OR ≈ 2.0–2.5), with antibiotic and PPI exposure as key cofactors. “4C” antibiotic use in diabetic foot ulcer patients quintupled CDI risk. Metabolic decompensation, such as diabetic ketoacidosis (DKA), significantly elevated mortality (5.8 % vs 2.7 %) and LOS. Conversely, metformin therapy reduced CDI odds by ~42 %, likely through gut-microbiota modulation. Diabetic patients with cholera showed prolonged hospitalization (IRR ≈ 2.0) without excess mortality. NOS scores (6–8/9) indicated moderate–high methodological quality.

Conclusion:

Diabetes amplifies susceptibility and worsens outcomes of CDI and related enteric infections, while metformin may offer partial protection. Incorporating glycaemic optimization, antibiotic stewardship, and microbiome-preserving strategies into diabetic care could mitigate infection-related morbidity and healthcare burden.