The subgingival microbiome, systemic inflammation and insulin resistance: The Oral Infections, Glucose Intolerance and Insulin Resistance Study

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 P046: The Subgingival Microbiome, Systemic Inflammation and Insulin Resistance

Circulation ◽

10.1161/circ.133.suppl_1.p046 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Ryan T Demmer ◽

Alexander Breskin ◽

Michael Rosenbaum ◽

Aleksandra Zuk ◽

Charles LeDuc ◽

...

Keyword(s):

Insulin Resistance ◽

Systemic Inflammation ◽

Venous Blood ◽

Linear Regression Models ◽

P Values ◽

Oral Infections ◽

Mediation Analyses ◽

Inflammatory Score ◽

Inflammatory Phenotype ◽

Factor Α

Introduction: Chronic inflammation is hypothesized as a mechanism linking microbial exposures to insulin resistance. We investigated the association between periodontal microbiota, systemic inflammation and insulin resistance among diabetes-free adults. Hypotheses: We hypothesized that subgingival microbial signatures would be related to both inflammatory phenotype and measures of insulin resistance and that there would be evidence of mediation by inflammatory markers. Methods: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 152 diabetes-free adults (77% female) aged 20-55 years (mean=34±10). 304 subgingival plaque samples (2 per participant) were analyzed using the Human Oral Microbe Identification Microarray (HOMIM) to measure the relative abundances of 379 taxa from eight different phyla. C-reactive protein, interleukin-6, tumor necrosis factor-α and adiponectin were assessed from venous blood and their z-scores were summed to create an inflammatory score (IS). Fasting glucose and insulin levels defined insulin resistance via the HOMA-IR. Associations between the subgingival microbiota and both inflammation and insulin resistance were explored using multivariable linear regression models adjusted for cardiometabolic risk factors; mediation analyses assessed the proportion of the association explained by inflammation. Results: The IS was inversely associated with the relative abundance of Actinobacteria and Proteobacteria and positively associated with Firmicutes and TM7 (all p-values<0.05). The IS was positively associated with glucose, insulin and HOMA-IR (all p<0.05). Proteobacteria levels were associated with insulin resistance (p<0.05). Inflammation explained 30%-98% of the observed associations between levels of Actinobacteria, Proteobacteria or Firmicutes and insulin resistance (p-values<0.05). 18 individual taxa were associated with inflammation (p<0.05) and 22 with insulin resistance (p<0.05). Conclusion: Subgingival microbial community structure and membership were related to systemic inflammation and insulin resistance in a sample of diabetes-free adults.

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

PLoS ONE ◽

10.1371/journal.pone.0227482 ◽

2020 ◽

Vol 15 (1) ◽

pp. e0227482 ◽

Cited By ~ 1

Author(s):

Sumith Roy ◽

Melana Yuzefpolskaya ◽

Renu Nandakumar ◽

Paolo C. Colombo ◽

Ryan T. Demmer

Keyword(s):

Insulin Resistance ◽

Glucose Intolerance ◽

Glucose Regulation ◽

Impaired Glucose Regulation ◽

Oral Infections

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Differential Roles of Water–Insoluble and –Soluble Fractions of Diesel Exhaust Particles in the Development of Adverse Health Effects due to Chronic Instillation of Diesel Exhaust Particles

10.21203/rs.3.rs-527024/v1 ◽

2021 ◽

Author(s):

Yanyi Xu ◽

Zhouzhou Li ◽

Ying Liu ◽

Bin Pan ◽

Renzheng Peng ◽

...

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

Hepatic Steatosis ◽

Glucose Intolerance ◽

Systemic Inflammation ◽

Diesel Exhaust ◽

Cell Number ◽

Diesel Exhaust Particles ◽

Water Soluble ◽

Exhaust Particles

Abstract Background: Ambient fine particulate matter (PM2.5) has a marked temporospatial variation in chemical composition, but how the composition of PM2.5 influences its toxicity remains elusive. Results: To explore the individual roles of different PM2.5 components in the pathogenesis due to PM2.5 exposure, we prepared water-soluble (WS-DEP) and -insoluble (WIS-DEP) fractions of diesel exhaust particles (DEP) and assessed their effects on pulmonary and systemic inflammation, hepatic steatosis and insulin resistance, systemic glucose homeostasis, and gut microbiota using chronic intratracheal instillation mouse models. Compared to control, instillation of DEP or WIS-DEP, but not WS-DEP, significantly increased pulmonary inflammatory scores and expression of inflammatory markers, bronchoalveolar lavage fluid cell number, and circulating pro-inflammatory cytokines. Consistently, DEP or WIS-DEP-instilled but not WS-DEP-instilled mice versus control had significant hepatic steatosis and insulin resistance and systemic glucose intolerance. In contrast, instillation of WS-DEP versus instillation of WIS-DEP had more similar effects on gut microbiota to that of instillations of DEP. Conclusion: The pulmonary and systemic inflammation, hepatic steatosis and insulin resistance, and systemic glucose intolerance following chronic DEP instillation are all attributable to the water-insoluble fraction of DEP, providing a mechanistic interpretation for the apparent independency of PM2.5 exposure-induced glucose intolerance on PM2.5 composition.

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Female 5[beta]-reductase knockout mice are protected from diet induced obesity, insulin resistance and glucose intolerance

Endocrine Abstracts ◽

10.1530/endoabs.41.oc12.2 ◽

2016 ◽

Author(s):

Laura Gathercole ◽

Matthew Chapman ◽

Dean Larner ◽

Petra Klusonova ◽

Trevor Penning ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Intolerance ◽

Knockout Mice ◽

Diet Induced Obesity

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Faculty Opinions recommendation of Muscle-specific Pikfyve gene disruption causes glucose intolerance, insulin resistance, adiposity, and hyperinsulinemia but not muscle fiber-type switching.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718014202.793477662 ◽

2013 ◽

Author(s):

Alex Toker ◽

Kristin Brown

Keyword(s):

Insulin Resistance ◽

Glucose Intolerance ◽

Muscle Fiber ◽

Gene Disruption ◽

Fiber Type ◽

Muscle Fiber Type

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P1279INSULIN RESISTANCE IN HEMODIALYSIS PATIENS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1279 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Pavel Filinyuk ◽

Aleksander Rumyantsev

Keyword(s):

Insulin Resistance ◽

Systemic Inflammation ◽

Clinical Manifestations ◽

Biological Response ◽

Fold Increase ◽

Atherogenic Dyslipidemia ◽

Model Assessment ◽

Peripheral Tissues ◽

Reactive Protein ◽

Homeostatic Model Assessment

Abstract Background and Aims insulin resistance (IR) is a decrease in the biological response of sensitive tissues to insulin. IR is known as an adverse risk factor in cardiovascular disease, which largely determines the prognosis of patients receiving hemodialysis (HD). But this issue is not well understood. For the screening of IR, special indices have been developed that characterize the sensitivity of tissues to insulin. The aim of the study was to compare the methods of screening for IR in patients receiving HD in relation to the markers of systemic inflammation and atherogenic dyslipidemia (AtD). Method 124 patients receiving HD for 75.4 ± 44.5 months were examined including 66 men and 58 women aged 57.6 ± 13.6 years. For IR screening, the Homeostatic Model Assessment-1 and 2 indices (HOMA-1 and HOMA-2), the Quantitative Insulin Sensitivity Check Index (QUICKI) and triglycerides / glucose (Tri/G) were used. Patients were examined in accordance with the recommendations of KDIGO. Data analysis was carried out using “STATISTICA 10.0”. Results fasting insulin levels were elevated in 19% of patients. But, the calculated indices were consistent with the idea that IR is much more common. So, the IR index in the HOMA -1 model was increased in 47%, in the HOMA -2 model - in 33%, in the QUICKI model - in 36%, the TriH indicator - in 91%. The sensitivity of peripheral tissues in the HOMA-1 and HOMA-2 models was equally reduced by 35-40%. The results of the correlation analysis between indicators of IR and plasma concentration of C-reactive protein and lipid profile are presented in table 1. Informativeness of IR indicators depending on the presence of obesity is presented in table 2 We were also interested in whether insulin resistance affects the development of clinical manifestations of atherosclerosis, cardiac arrhythmias, and heart failure. An analysis of this relationship did not reveal. Only the IR index in the HOMA-1 model with a value of more than 2.7 units was associated with a 4.5-fold increase in the risk of developing clinical manifestations of atherosclerotic lesions (χ2 = 4.582 p = 0.032). Statistically significant it was only in men. Given our data, perhaps IR is one of the reasons for the higher morbidity and mortality of men at HD. Conclusion a comparison of IR models allows us to distinguish HOMA-2 as the most accurate index. The highest correlation with systemic inflammation and AtD was in the HOMA-1 and HOMA-2 indices.

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