Saliva and Plasma Reflect Metabolism Altered by Diabetes and Periodontitis

Periodontitis is an inflammatory disorder caused by disintegration of the balance between the periodontal microbiome and host response. While growing evidence suggests links between periodontitis and various metabolic disorders including type 2 diabetes (T2D), non-alcoholic liver disease, and cardiovascular disease (CVD), which often coexist in individuals with abdominal obesity, factors linking periodontal inflammation to common metabolic alterations remain to be fully elucidated. More detailed characterization of metabolomic profiles associated with multiple oral and cardiometabolic traits may provide better understanding of the complexity of oral-systemic crosstalk and its underlying mechanism. We performed comprehensive profiling of plasma and salivary metabolomes using untargeted gas chromatography/mass spectrometry to investigate multivariate covariation with clinical markers of oral and systemic health in 31 T2D patients with metabolic comorbidities and 30 control subjects. Orthogonal partial least squares (OPLS) results enabled more accurate characterization of associations among 11 oral and 25 systemic clinical outcomes, and 143 salivary and 78 plasma metabolites. In particular, metabolites that reflect cardiometabolic changes were identified in both plasma and saliva, with plasma and salivary ratios of (mannose + allose):1,5-anhydroglucitol achieving areas under the curve of 0.99 and 0.92, respectively, for T2D diagnosis. Additionally, OPLS analysis of periodontal inflamed surface area (PISA) as the numerical response variable revealed shared and unique responses of metabolomic and clinical markers to PISA between healthy and T2D groups. When combined with linear regression models, we found a significant correlation between PISA and multiple metabolites in both groups, including threonate, cadaverine and hydrocinnamate in saliva, as well as lactate and pentadecanoic acid in plasma, of which plasma lactate showed a predominant trend in the healthy group. Unique metabolites associated with PISA in the T2D group included plasma phosphate and salivary malate, while those in the healthy group included plasma gluconate and salivary adenosine. Remarkably, higher PISA was correlated with altered hepatic lipid metabolism in both groups, including higher levels of triglycerides, aspartate aminotransferase and alanine aminotransferase, leading to increased risk of cardiometabolic disease based on a score summarizing levels of CVD-related biomarkers. These findings revealed the potential utility of saliva for evaluating the risk of metabolic disorders without need for a blood test, and provide evidence that disrupted liver lipid metabolism may underlie the link between periodontitis and cardiometabolic disease.Sakanaka A., Kuboniwa M., Katakami N., et al. Saliva and Plasma Reflect Metabolism Altered by Diabetes and Periodontitis. Frontiers in Molecular Biosciences, 8, , 742002. https://doi.org/https://doi.org/10.3389/fmolb.2021.742002

Salivary metabolic signatures of carotid atherosclerosis in patients with type 2 diabetes hospitalized for treatment

Atherosclerosis is a life-threatening disease associated with morbidity and mortality in patients with type 2 diabetes (T2D). This study aimed to characterize a salivary signature of atherosclerosis based on evaluation of carotid intima-media thickness (IMT) to develop a non-invasive predictive tool for diagnosis and disease follow-up. Metabolites in saliva and plasma samples collected at admission and after treatment from 25 T2D patients hospitalized for 2 weeks to undergo medical treatment for diabetes were comprehensively profiled using metabolomic profiling with gas chromatography-mass spectrometry. Orthogonal partial least squares analysis, used to explore the relationships of IMT with clinical markers and plasma and salivary metabolites, showed that the top predictors for IMT included salivary allantoin and 1,5-anhydroglucitol (1,5-AG) at both the baseline examination at admission and after treatment. Furthermore, though treatment induced alterations in salivary levels of allantoin and 1,5-AG, it did not modify the association between IMT and these metabolites (pinteraction > 0.05), and models with these metabolites combined yielded satisfactory diagnostic accuracy for the high IMT group even after treatment (area under curve = 0.819). Collectively, this salivary metabolite combination may be useful for non-invasive identification of T2D patients with a higher atherosclerotic burden in clinical settings.Sakanaka A, Katakami N, Furuno M, Nishizawa H, Omori K, Taya N, Ishikawa A, Mayumi S, Inoue M, Tanaka Isomura E, Amano A, Shimomura I, Fukusaki E and Kuboniwa M (2022) Salivary metabolic signatures of carotid atherosclerosis in patients with type 2 diabetes hospitalized for treatment. Front. Mol. Biosci. 9:1074285. doi: 10.3389/fmolb.2022.107428

Periodontal tissue susceptibility to glycaemic control in type 2 diabetes

Inoue M., Sakanaka A., Katakami N., et al. Periodontal tissue susceptibility to glycaemic control in type 2 diabetes. Diabetes, Obesity and Metabolism 26, 4684 (2024); https://doi.org/10.1111/dom.15835.Aim: To assess the direct effect of intensive glycaemic control on periodontal tissues in patients with diabetes mellitus. Materials and Methods: Twenty-nine patients with type 2 diabetes were enrolled and hospitalized to receive a 2-week intensive glycaemic control regimen. We observed and analysed the systemic and oral disease indicators before and after treatment and clarified the indicators related to periodontal inflammation. Results: A significant reduction in glycaemic and periodontal parameters, including glycated albumin levels and periodontal inflamed surface area (PISA), was observed after treatment. The changes in PISA per tooth, indicative of periodontal healing, exhibited a bimodal distribution; the patients were divided into two groups on this basis. Correlations were observed between the changes in PISA per tooth and fasting plasma glucose, acetoacetic acid, and beta-hydroxybutyrate levels in the PISA-improved group. Significantly lower levels of C-peptide, coefficient of variation of R-R interval, and ankle-brachial pressure index were observed before treatment in the PISA non-improved group. Conclusions: Glycaemic control treatment can effectively improve periodontitis in patients with type 2 diabetes, even in the absence of specific periodontal treatments. However, the periodontal responsiveness to glycaemic control treatment depends on the systemic condition of the patient

Late-onset paradoxical reactions 10 years after treatment for tuberculous meningitis in an HIV-negative patient: a case report

Abstract Background Although paradoxical reactions (PRs) to anti-tuberculosis (anti-TB) therapy during treatment are well-established occurrences, PRs presenting as a new lesion after the completion of treatment are extremely rare, and little is known about the management of such cases, particularly of central nervous system (CNS) tuberculosis. Case presentation A 27-year-old female, with a past medical history of tuberculous meningitis 10 years ago and who completed the anti-TB treatment with asymptomatic remnant tuberculomas in the basal cistern, was admitted to our hospital because of a headache and the worsening of pre-existing visual disturbance. Contrast-enhanced T1-weighted brain magnetic resonance imaging (MRI) revealed new tuberculomas in the left sylvian fissure with a diffuse low signal around it. Because repeated polymerase chain reaction and Mycobacterium tuberculosis culture presented negative results and the patient had no laboratory data suggestive of a relapse of tuberculous meningitis, she was diagnosed with late-onset post-treatment PRs and treated with oral corticosteroids, tapered off over 1 year. Eventually, the symptoms were relieved, and the tuberculomas disappeared. Conclusions Clinicians should consider the possibility of PRs long after the completion of tuberculous meningitis treatment. Hence, a precise MRI-based examination is imperative for the follow-up of CNS tuberculosis, and the unnecessary administration of anti-TB drugs should be avoided. The use of corticosteroids as a treatment option for post-treatment PRs is seemingly safe when the isolated M. tuberculosis is sensitive to the first-line anti-TB therapy