Exposure to Porphyromonas gingivalis and Modifiable Risk Factors Modulate Risk for Early Diabetic Retinopathy

Abstract

Purpose: We hypothesized that exposure to Porphyromonas gingivalis (Pg) increases the risk for early diabetic retinopathy (DR) and that the risk can be modulated.

Methods: We identified 116 early DR cases, and 116 non-DR controls were selected randomly by frequency matching for age, sex, race, and education from the US Third National Health and Nutrition Examination Survey. DR was assessed using non-mydriatic fundus photographs and graded by trained graders using the Modified Airlie House Classification scheme and the Early Treatment for Diabetic Retinopathy Study severity scale. Serum Pg immunoglobulin G (IgG) antibody (Ab) was measured in enzyme-linked immunosorbent assay units. Logistic regression was used to relate serum Pg IgG Ab levels to the risk for early DR.

Results: Per tenfold increase in Pg IgG Ab levels, there was an over 60% increased risk for early DR (odds ratio = 1.64; 95% confidence interval, 1.36-1.97), and a linear trend was noted for the estimated probabilities of early DR at various Pg IgG Ab levels (P for trend = 0.0053). The analysis also suggested that moderate alcohol consumption (less than 12 drinks in the past 12 months; P for interaction = 0.0003) and maintaining a normal serum glycated hemoglobulin level (HbA1c ≤ 5.7%; P for interaction < 0.0001) helped reduce the Pg-related DR risk.

Conclusions: The increased Pg-related DR risk could be alleviated by managing alcohol consumption and maintaining a normal blood glucose level.

Translational relevance: Findings from this study provide new directions for developing novel therapeutics and prevention strategies for DR.

Figure 1.

Logistic regression was used to calculate estimated probabilities for early DR at various Pg IgG Ab levels. The model was adjusted for age, sex, race, education, BMI, smoking history, alcohol drinking status, serum CRP and HbA1c levels, hypertension, mBOP, and mCAL. Forty-one non-drinkers were excluded from the analysis. The Pg IgG Ab levels were log₁₀ transformed. The estimated probabilities for early DR at various Pg IgG Ab levels and the fitted linear regression line are shown (regression coefficient β = 0.06192; P for trend = 0.0053).

Figure 2.

Pg-related early DR risk significantly varied by the four combinations of alcohol drinking status (moderate or excessive drinking) and serum HbA1c status (high, HbA1c > 5.7 DCCT%; normal, HbA1c ≤ 5.7 DCCT%) (interaction β = 0.27; P for interaction < 0.0001). Shown are the estimated probabilities and fitted linear regression lines for (A) excessive drinking and high HbA1c (β = 0.11882; P for trend < 0.0001) vs. (B) excessive drinking and normal HbA1c (β = 0.00985; P for trend < 0.0001) vs. (C) moderate drinking and high HbA1c (β = 0.03317; P for trend < 0.0001) vs. (D) moderate drinking and normal HbA1c (β = 0.04695; P for trend < 0.0001). PGMX, a mixed suspension of Pg ATCC strains 33277 and 53978.