Periodontitis as a promoting factor of T2D: current evidence and mechanisms

Abstract

Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response. Epidemiologically, periodontitis is closely related to the occurrence, development, and poor prognosis of T2D and is recognized as a potential risk factor for T2D. In recent years, increasing attention has been given to the role of the virulence factors produced by disorders of the subgingival microbiota in the pathological mechanism of T2D, including islet β-cell dysfunction and insulin resistance (IR). However, the related mechanisms have not been well summarized. This review highlights periodontitis-derived virulence factors, reviews how these stimuli directly or indirectly regulate islet β-cell dysfunction. The mechanisms by which IR is induced in insulin-targeting tissues (the liver, visceral adipose tissue, and skeletal muscle) are explained, clarifying the influence of periodontitis on the occurrence and development of T2D. In addition, the positive effects of periodontal therapy on T2D are overviewed. Finally, the limitations and prospects of the current research are discussed. In summary, periodontitis is worthy of attention as a promoting factor of T2D. Understanding on the effect of disseminated periodontitis-derived virulence factors on the T2D-related tissues and cells may provide new treatment options for reducing the risk of T2D associated with periodontitis.

Current scientific evidence for why periodontitis should be included in diabetes management

“…The chronic, repetitious discharge of periodontal microbes and their byproducts into the bloodstream causes inflammatory markers to circulate and hence create or exacerbate insulin resistance ( 87 – 91 ) and DM complications ( 92 , 93 ).…”

“…Periodontal treatment decreases levels of several inflammatory biomarkers, many of which in turn are risk factors for DM complications like atherosclerosis and myocardial infarction, such as c-reactive protein ( 134 ) interleukin-(IL)-1beta ( 91 ), IL-6 ( 91 ), tumor necrosis factor-alpha (TNF-alpha) ( 91 ). Statistically significant decreases in the concentration of the active inflammatory marker, c-reactive protein, from baseline to each 3-monthly visit up to 1 year upon extraction of terminally periodontally diseased teeth and scaling and root planing the remaining dentition are reported ( 134 ).…”

Contribution of individual and cumulative social determinants of health underlying gender disparities in periodontitis in a representative US population: A cross‐sectional NHANES study

“…Approximately 10% of adults worldwide were affected in its severe form (Bernabe et al, 2020), and there were over 42 million individuals affected by severe periodontitis in the United States in 2019 compared with 28.3 million in 1990 (Chen et al, 2021). Periodontal disease is a risk factor for systemic diseases such as diabetes, cardiovascular diseases and cancer (Nwizu et al, 2020;Sanz et al, 2020;Su et al, 2023). In 2018, periodontal disease caused an estimated loss of $154.06 billion in the United States, imposing a heavy medical burden (Botelho et al, 2022).…”

Chronic periodontitis induces the proliferation of pancreatic β‐cells to cause hyperinsulinemia in a rat model

“…Epidemiological investigations have revealed that systemically healthy subjects with CP often show altered parameters related to β‐cell function, such as elevated homeostasis model assessment (HOMA) β index (HOMA‐β) values 6 and hyperinsulinemia 7 . Data from animal experiments have shown that periodontitis‐derived toxic products can interfere with β‐cell function 5 and have adverse effects on the metabolism of peripheral insulin‐targeting tissues, such as visceral adipose tissue, liver, and skeletal muscle, 4,8–10 which is an important cause of hyperinsulinemia or/and insulin resistance (IR). Recent study has demonstrated that the toxic product lipopolysaccharide (LPS) secreted by periodontal pathogens, Porphyromonas gingivalis ( P. gingivalis ), can cause endotoxemia and promote insulin secretion, which leads to hyperinsulinemia, 11 but the precise mechanism remains unclear.…”