Periodontitis as a potential amplifier of diabetes-related genitourinary complications: evidence gradients and mechanistic insights into the inflammation–microvascular injury axis

Periodontitis is increasingly recognized as a chronic systemic inflammatory burden that may be associated with greater vulnerability to selected diabetes-related genitourinary complications through overlapping inflammatory and microvascular pathways. This review integrates current epidemiological, mechanistic, and clinical evidence and proposes a conceptual "oral-metabolic-genitourinary axis" to describe potential links between periodontal inflammation and diabetic kidney disease (DKD), diabetes-related erectile dysfunction (ED), and recurrent urinary tract infections (UTIs). Available evidence is strongest for renal endpoints: observational studies and recent cohort data suggest associations between periodontitis and albuminuria, renal function decline, or dialysis risk in patients with type 2 diabetes. In contrast, evidence for ED and recurrent UTIs remains limited, with much of the support derived from mechanistic inference and indirect clinical observations. The proposed biologically plausible pathways include amplification of chronic low-grade systemic inflammation, endothelial and microvascular dysfunction, oxidative stress, advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling, and microbiome interactions involving the oral-gut-genitourinary axis. These proposed associations and pathways may be modified or intensified by poor glycemic control, obesity, smoking, vitamin D deficiency, and gut dysbiosis. Clinically, periodontal therapy has been associated with improved glycemic control and may improve selected inflammatory or renal-related surrogate indicators, suggesting that oral health management could be considered a supportive component of multidisciplinary diabetes care. Overall, periodontitis is best viewed at present as a plausible amplifying factor rather than a confirmed independent cause of these outcomes, and this hypothesis requires confirmation in large prospective cohorts, randomized trials, and multi-omics studies.