scholarly journals Subgingival Microbiota and Longitudinal Glucose Change: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS)

2019 ◽  
Vol 98 (13) ◽  
pp. 1488-1496 ◽  
Author(s):  
R.T. Demmer ◽  
P. Trinh ◽  
M. Rosenbaum ◽  
G. Li ◽  
C. LeDuc ◽  
...  

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.

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Ryan T Demmer ◽  
Pauline Trinh ◽  
Michael Rosenbaum ◽  
Charles LeDuc ◽  
Rudolph Leibel ◽  
...  

Background: Microbial dysbiosis and translocation of microbial products across digestive tract mucosal surfaces are hypothesized risk factors for impaired glucose regulation. We specifically investigated whether measures of subgingival dysbiosis predicted longitudinal fasting plasma glucose (FPG) change. Methods: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 300 diabetes-free adults (77% female) aged 20-55 years (mean±SD=34±10). Subgingival plaque samples were collected and analyzed using 16S rDNA sequencing (Illumina MiSeq; NexGEN) using the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) protocol. FPG was measured at baseline and after two-years. Microbial community alpha-diversity was calculated using Simpson’s index. Multivariable linear regressions modeled 2-year glucose change on baseline relative abundance of 376 individual oral taxa (in separate models) with adjustment for age, sex, race/ethnicity, education, smoking status, BMI and baseline glucose levels. All taxa with a p-value<0.05 were used to construct a microbial dysbiosis-index (MD-index) defined as the ratio of taxa abundance in organisms positively vs. inversely associated with FPG change. The MD-index was subsequently used in regression models to predict glucose change. Statistical significance was based on a false discovery rate (FDR)<0.05 or a Bonferroni corrected p-value (1x10 -4 ). Results: Mean 2-year FPG change±SD was 1.5±8 mg/dl. Mean±SD values of MD-index were 2.2±2.4. Baseline levels of 23 taxa were associated with FPG change (p<0.05), 11 of which had inverse associations. Among these 23 taxa, Treponema HOT238, Leptotrichia HOT498 and Stomatobaculum HOT097 had an FDR<0.05. The MD-index was inversely correlated with alpha-diversity (r=-0.19, p<0.01). Mean FPG-change±SE in the 3 rd vs. 1 st tertile of MD-index were 4.5±0.9 vs. -1.6±0.9 (p<1x10 -4 ). Conclusion: Increased levels of microbial dysbiosis, reflecting decreased microbial diversity, were associated with increased 2-year glucose change among young, diabetes-free subjects.


2021 ◽  
Vol 48 (5) ◽  
pp. 638-647
Author(s):  
Francesco DeMayo ◽  
Rebecca Molinsky ◽  
Muna J. Tahir ◽  
Sumith Roy ◽  
Jeanine M. Genkinger ◽  
...  

2003 ◽  
Vol 149 (4) ◽  
pp. 331-335 ◽  
Author(s):  
JV Silha ◽  
M Krsek ◽  
JV Skrha ◽  
P Sucharda ◽  
BL Nyomba ◽  
...  

OBJECTIVE: Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. METHODS: We examined plasma levels of resistin, adiponectin and leptin in 17 lean subjects with a mean body mass index (BMI) of approximately 23 and 34 non-diabetic obese individuals with a mean BMI approximately 33. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. RESULTS: Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 35.4+/-6.5 (s.e.) vs 15.4+/-2.9 microg/L, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P<0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly lower in obese compared with lean subjects, P<0.005, and higher in women, P<0.001, but showed no significant correlation with HOMA-R. Leptin levels were significantly higher in obese subjects and women and correlated with HOMA-R and resistin. DISCUSSION: In this small group of patients we demonstrated that insulin resistance correlated most strongly with leptin levels. A significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for adiponectin, the correlation with insulin resistance did not achieve statistical significance.


Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4136-4145 ◽  
Author(s):  
Geetanjali Sharma ◽  
Chelin Hu ◽  
Jonathan L. Brigman ◽  
Gang Zhu ◽  
Helen J. Hathaway ◽  
...  

Estrogen is an important regulator of metabolic syndrome, a collection of abnormalities including obesity, insulin resistance/glucose intolerance, hypertension, dyslipidemia, and inflammation, which together lead to increased risk of cardiovascular disease and diabetes. The role of the G protein-coupled estrogen receptor (GPER/GPR30), particularly in males, in these pathologies remains unclear. We therefore sought to determine whether loss of GPER contributes to aspects of metabolic syndrome in male mice. Although 6-month-old male and female GPER knockout (KO) mice displayed increased body weight compared with wild-type littermates, only female GPER KO mice exhibited glucose intolerance at this age. Weight gain in male GPER KO mice was associated with increases in both visceral and sc fat. GPER KO mice, however, exhibited no differences in food intake or locomotor activity. One-year-old male GPER KO mice displayed an abnormal lipid profile with higher cholesterol and triglyceride levels. Fasting blood glucose levels remained normal, whereas insulin levels were elevated. Although insulin resistance was evident in GPER KO male mice from 6 months onward, glucose intolerance was pronounced only at 18 months of age. Furthermore, by 2 years of age, a proinflammatory phenotype was evident, with increases in the proinflammatory and immunomodulatory cytokines IL-1β, IL-6, IL-12, TNFα, monocyte chemotactic protein-1, interferon γ-induced protein 10, and monokine induced by interferon gamma and a concomitant decrease in the adipose-specific cytokine adiponectin. In conclusion, our study demonstrates for the first time that in male mice, GPER regulates metabolic parameters associated with obesity and diabetes.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Yoshihiro Kokubo ◽  
Makoto Watanabe ◽  
Aya Higashiyama ◽  
Yoko M Nakao ◽  
Takashi Kobayashi ◽  
...  

Introduction: Glucose intolerance and insulin resistance are known risk factors for cardiovascular disease (CVD). However, few prospective studies were reported the association between combinations of these two factors and incident CVD. We assessed the hypothesis that insulin resistance increased the association between glucose intolerance and CVD in Japanese general population. Methods: We studied 4,638 Japanese individuals (mean age 56.1 years, without CVD) who completed a baseline medical examination and a 75g oral glucose tolerance test in the Suita Study. Glucose categories were defined as follows: diabetes mellitus (DM; fasting plasma glucose levels [FPG] ≥126 mg/dL, 2 hours post-loaded glucose levels [2h-PG] ≥ 200 mg/dL, and/or DM medication); impaired glucose tolerance (IGT; FPG <126 mg/dL and 2h-PG =140-199 mg/dL); impaired fasting glucose (IFG; FPG =100-125 mg/dL and 2h-PG <140 mg/dL); and normal glucose tolerance [NGT]. Insulin resistance was the following formula: HOMA-IR = [FPG] x [fasting insulin] / 405. Insulin resistance was defined as HOMA-IR ≥2.5. Multivariable-adjusted Cox proportional hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated after adjusting for age, sex, body mass index, blood pressure category, hyperlipidemia, smoking, and drinking at the baseline. Results: During the 11.7-year follow-up, we documented 127 cerebral infarctions, 63 hemorrhagic stroke, 12 unclassified strokes, and 143 coronary heart disease events. The adjusted HRs (95% CIs) of subjects with FPG =100-125 mg/dL and ≥126 mg/dL were 1.38 (1.01-1.89) and 2.00 (1.12-3.58) for stroke and 1.47 (0.99-2.19) and 2.73 (1.43-5.22) for cerebral infarction, respectively, compared with the fasting NGT group. On the basis of the subjects with 2h-PG <140 mg/dL group, the adjusted HRs (95% CIs) of subjects with 2h-PG ≥200 mg/dL were 1.71 (1.07-2.72) for stroke and 2.06 (1.20-3.54) for cerebral infarction. Compared to the NGT group, the adjusted HRs (95% CIs) of the subjects with IFG, IGT, and DM were 1.59 (1.10-2.30), 1.34 (0.89-2.00), and 1.86 (1.16-3.00) for stroke and 1.82 (1.13-2.90), 1.55 (0.93-2.56), and 2.43 (1.39-4.26) for cerebral infarction, respectively. Compared to the subjects with HOMA-IR <1.5, the adjusted HRs (95% CIs) of CVD and stroke with HOMA-IR ≥2.5 were 1.45 (1.07-1.96) and 1.61 (1.07-2.42), respectively. Compared to the NGT group without insulin resistance, the IFG and DM groups with insulin resistance were observed the increased risks of stroke (HRs [95% CIs]; 2.05 [1.17-3.57] and 2.11 [1.17-3.83]) and cerebral infarction (HRs [95% CIs]; 2.45 [1.20-5.00] and 3.56 [1.84-6.88]), respectively. Conclusions: Fasting glucose intolerance and insulin resistance are predictive factors for the incidence of stroke and cerebral infarction. Insulin resistance increased the risks of incident stroke and cerebral infarction in general inhabitants with IFG and DM.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Ryan T Demmer ◽  
David R Jacobs ◽  
Richa Singh ◽  
Aleksandra Zuk ◽  
Michael Rosenbaum ◽  
...  

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.


2017 ◽  
Vol 44 (3) ◽  
pp. 255-265 ◽  
Author(s):  
Ryan T. Demmer ◽  
Alexander Breskin ◽  
Michael Rosenbaum ◽  
Aleksandra Zuk ◽  
Charles LeDuc ◽  
...  

PLoS ONE ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. e0227482 ◽  
Author(s):  
Sumith Roy ◽  
Melana Yuzefpolskaya ◽  
Renu Nandakumar ◽  
Paolo C. Colombo ◽  
Ryan T. Demmer

This study was designed to investigate changes in lipid profile and glucose levels in twenty albino rats fed with African walnut. The twenty albino rats were divided into four groups with five animals in each group. Group 1 were placed on normal diet, group 2,3 and 4 were given 1% cholesterol,1%cholesterol and 1% African walnut seed powder, and 1% cholesterol and 5% walnut seed powder respectively. The level of serum lipid and plasma glucose was carried out by spectrophotometric method. The results were analyzed for statistical significance using analysis of variance ANOVA, p-value < 0.05 were considered statistical significant. The level of total cholesterol increased in group 2(164.60 ± 7.09g) when compared to control (160.20±2.28g) at p<0.05.While a significant increase was seen in mean value of group 2(220.00±33.918mg/dl) and group 3(120.00±36.74mg/ dl) when compared to value of control (66.0±11.40mg/dl). Hence these observation indicate that supplementation of African walnut seed could be beneficial to patient with cardiovascular disease and diabetes.


2018 ◽  
Vol 31 (10) ◽  
pp. 1139-1146 ◽  
Author(s):  
Lakshmipathi Naik Banavath ◽  
Rakesh Kumar ◽  
Devi Dayal ◽  
Jaivinder Yadav ◽  
Naresh Sachdeva ◽  
...  

Abstract Background Cystic fibrosis-related diabetes (CFRD) is a common comorbidity reported in patients with cystic fibrosis (CF). There is a dearth of data on glucose intolerance or CFRD in children with CF from developing countries. So, we planned to study the prevalence of abnormal glucose tolerance (AGT) in children with CF and its relation with the duration and severity of CF. Methods We performed an oral glucose tolerance test (OGTT) on children (2–18 years old) having CF for at least 6 months. Two-hour plasma glucose levels on OGTT were correlated with various disease-related factors. Results Out of the 25 children enrolled, there were 18 boys and seven girls. The mean age and duration of CF were 7.9±4.3 and 3.16±2.5 years, respectively. AGT was observed in 16 (64%) children with CF including three (12%) children with CFRD. Children with a duration of CF of 3 years had significantly higher prevalence (81.8%) of AGT when compared with duration ≤3 years (p-value<0.05). Twelve out of 17 (70.6%) children were colonized with Pseudomonas and 12 out of 15 (80%) children >6 years of age had AGT. There was a positive correlation of 2-h glucose value on OGTT with duration of CF and number of hospitalizations with acute pulmonary exacerbations. Conclusions The majority of children having CF for >3 years and/or age >6 years developed AGT. In our clinical setting, an annual screening with OGTT to detect AGT may be required at an early age and duration of CF.


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