Obesity alters composition and diversity of the oral microbiota in patients with type 2 diabetes mellitus independently of glycemic control.

BACKGROUND AND OBJECTIVE: The involvement of the oral microbiota as a possible link between periodontitis, type 2 diabetes mellitus and obesity is still not well understood. The objective of the study was to investigate if glycemic control and obesity play a role in modulating the composition and diversity of the oral microbial ecology. MATERIAL AND METHODS: A cohort of patients with type 2 diabetes mellitus (n = 18) was recruited. Participants demonstrating improved glycemic control after 3 months (n = 6) were included in a second examination. A full mouth examination was performed to estimate periodontitis severity followed by sample collection (subgingival plaque and saliva). Generation of large sequence libraries was performed using the high-throughput Illumina MiSeq sequencing platform. RESULTS: The majority of participants (94.4%, n = 17) presented with moderate or severe forms of periodontitis. Differences in microbial composition and diversity between obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) groups were statistically significant. Cross-sectional and longitudinal approaches failed to reveal statistically significant associations between HbA1c level and species composition or diversity. CONCLUSIONS: Obesity was significantly associated with the oral microbial composition. The impact of glycemic control on oral microbiota, however, could not be assured statistically.

No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels.

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (ß = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (ß = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.

The pivotal role of scavenger receptor CD36 and phagocyte-derived oxidants in oxidized low density lipoprotein-induced adhesion to endothelial cells.

Adhesion of phagocytes to endothelial cells constitutes a crucial step in atherogenesis. Oxidized low density lipoproteins (LDL) are supposed to facilitate the adhesion process. We investigated the molecular mechanisms by which mildly and extensively hypochlorite-oxidized LDL force adhesion of murine macrophages and human neutrophils to human umbilical venous endothelial cells. After 1h of co-incubation of macrophages, endothelial cells, and lipoproteins adhesion significantly increased to 160+/-13% (S.E.M., n=5) in the presence of mildly oxidized lipoprotein, and 210+/-11% (S.E.M., n=5) in the presence of extensively oxidized lipoprotein. Similar results were obtained with neutrophils. CD36 antibody (FA6-152) significantly reduced adhesion to 102+/-7% (S.E.M., n=5) using mildly oxidized low density lipoprotein and to 179+/-16% (S.E.M., n=5) using extensively oxidized low density lipoprotein. Native high density lipoprotein and to a lesser extent methionine-oxidized high density lipoprotein significantly counteracted the effects of low density lipoprotein. Prior incubation of endothelial cells with modified lipoproteins followed by their removal and subsequent incubation with macrophages or neutrophils resulted in only minor changes of adhesion. This suggests that the direct contact of low density lipoprotein with phagocytes followed by activation of a respiratory burst with release of reactive oxygen species facilitates the adhesion process. Accordingly, the addition of antioxidants (superoxide dismutase and catalase) to the co-incubation medium was followed by a significant decrease in phagocyte adhesion. It is concluded that oxidized low density lipoprotein-induced respiratory burst activation of phagocytes with subsequent release of oxidants constitutes a crucial step in promoting the adhesion of phagocytes to endothelial cells.