Plasma Trimethylamine-N-oxide and impaired glucose regulation: Results from The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS)

Microbial communities along mucosal surfaces throughout the digestive tract are hypothesized as risk factors for impaired glucose regulation and the development of clinical cardiometabolic disease. We investigated whether baseline measures of subgingival microbiota predicted fasting plasma glucose (FPG) longitudinally. The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 230 diabetes-free adults (77% female) aged 20 to 55 y (mean ± SD, 34 ± 10 y) from whom baseline subgingival plaque and longitudinal FPG were measured. DNA was extracted from subgingival plaque, and V3 to V4 regions of the 16S rRNA gene were sequenced. FPG was measured at baseline and again at 2 y; glucose change was defined as follow-up minus baseline. Multivariable linear models regressed 2-y glucose change onto baseline measures of community diversity and abundances of 369 individual taxa. A microbial dysbiosis index (MDI) summarizing top individual taxa associated with glucose change was calculated and used in regression models. Models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and baseline glucose levels. Statistical significance was based on the false discovery rate (FDR; <0.05) or a Bonferroni-corrected P value of 1 × 10-4, derived from the initial 369 hypothesis tests for specific taxa. Mean 2-y FPG change was 1.5 ± 8 mg/dL. Baseline levels of 9 taxa predicted FPG change (all FDR <0.05), among which Stomatobaculum sp oral taxon 097 and Atopobium spp predicted greater FPG change, while Leptotrichia sp oral taxon 498 predicted lesser FPG change (all 3 P values, Bonferroni significant). The MDI explained 6% of variation in longitudinal glucose change ( P < 0.001), and baseline glucose levels explained 10% of variation ( P < 0.0001). FPG change values ± SE in the third versus first tertile of the MDI were 4.5 ± 0.9 versus 1.6 ± 0.9 ( P < 1 × 10-4). Subgingival microbiota predict 2-y glucose change among diabetes-free men and women.

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Abstract P342: Periodontal Bacteria, Prevalent Prediabetes and Plasma Glucose Progression: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS)

Circulation ◽

10.1161/circ.131.suppl_1.p342 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Ryan T Demmer ◽

David R Jacobs ◽

Richa Singh ◽

Aleksandra Zuk ◽

Michael Rosenbaum ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Intolerance ◽

Plasma Glucose ◽

Cardiometabolic Risk ◽

Bacterial Species ◽

Early Diabetes ◽

Oral Infections ◽

Actinomyces Naeslundii ◽

Longitudinal Plasma

Introduction: Periodontal infections have been hypothesized as a cardiometabolic risk factor. The relationship between periodontal microbiota and early diabetes risk has not been studied. Hypothesis: We hypothesized that periodontopathic bacteria would be associated with both prevalent pre diabetes and accelerated longitudinal plasma glucose progression among diabetes-free adults. Methods: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 300 diabetes-free adults (77% female) aged 20-55 years (mean=34±10). Prevalent prediabetes was defined as: i) 5.6%<HbA1C<6.5%; or ii) 99 mg/dL<fasting plasma glucose (FPG)<126 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species including Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Treponema denticola (Td), Tannerella forsythia (Tf) and Actinomyces naeslundii (An) were assessed at baseline. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Risk ratios (RR), 95% confidence intervals (CI) for 3rd vs. 1st tertile are presented. Follow-up is ongoing but longitudinal FPG was available for interim analysis among the first n=100 recall-eligible participants (mean follow-up time=2±0.3 years). Mixed-effects regressions evaluated FPG time trends across baseline bacterial levels. All analyses were adjusted for cardiometabolic risk factors. Results: Prediabetes prevalence was 18% (54 of 300). RRs(95%CI) summarizing associations between bacteria and pre diabetes were as follows: Aa=2.48[1.34,4.58], p=0.004; Pg=3.41[1.78,6.58], p=0.0003; Td=1.99[0.992,4.00], p=0.052 and Tf=1.95[1.0,3.84], p=0.05; An=0.46[0.25,0.85], p=0.01. Among participants with high baseline values of Pg or Tf, FPG increased by ~2.5 mg/dl during follow-up (all p-values<0.05) while no FPG progression was observed among participants with low baseline bacterial levels. Conclusion: Periodontopathic microbiota are associated with both prevalent prediabetes and longitudinal plasma glucose increase among diabetes-free adults.

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