Aims. Hashimoto’s thyroiditis (HT), a type of autoimmune disease, occurs due to genetic predisposition and environmental factors. It is well known that thyroid function may affect the gut microbiota. However, the composition of gut microbiota in HT patients with different thyroid function status has been less highlighted. Therefore, we focused on the alterations in the composition of gut microbiota in HT patients with euthyroidism and hypothyroidism. Methods. We performed a cross-sectional study, including 45 HT patients with euthyroidism, 18 HT patients with hypothyroidism, and 34 healthy controls. Fecal samples were collected, and microbiota was examined by using 16S RNA ribosomal RNA gene sequencing. Then, we analyzed the possible pathways in relation to the enriched bacteria by linear discriminant analysis (LDA) effect size (LEfSe). Results. Compared with the controls, bacterial richness and diversity were significantly lower in patients with HT, especially in hypothyroidism. Moreover, Lachnospiraceae_incertae_sedis, Lactonifactor, Alistipes, and Subdoligranulum were more enriched in HT patients with euthyroidism, while Phascolarctobacterium was more abundant in those with hypothyroidism. Further analysis suggested that Phascolarctobacterium was negatively related to several pathways, including environmental information processing and metabolism. Conclusion. In summary, our study demonstrated the altered composition of gut microbiota in HT patients with different thyroid function status. Moreover, Phascolarctobacterium may be involved in the development of HT.

Background: Although the prognosis for most patients with papillary thyroid cancer (PTC) is good, the present treatment is ineffective for 5–10% patients. Several studies found sodium–glucose cotransporter 2 (SGLT2) inhibitors may inhibit the growth of tumors. However, whether SGLT2 inhibitors have therapeutic effect on thyroid cancer remains unclear.Materials and methods: The levels of SGLT2 in PTC and normal thyroid tissue were assessed by immunohistochemistry and clinical dataset analysis. Cell growth was detected by the CCK-8 and colony formation. Glucose uptake into thyroid cancer cell was evaluated by 2-DG uptake assay. Glycolysis were analyzed by Seahorse XF Extracellular Flux Analysis. RNA-seq were used to screen differentially expressed genes of cells treated with/without canagliflozin (a SGLT2 inhibitor). Furthermore, flow cytometry, western blot, and gene set enrichment analysis were employed to elucidate cell cycle, apoptosis and the underlying mechanism of the anticancer effect of canagliflozin. The effect of canagliflozin on thyroid cancer growth was further confirmed in vivo through xenograft formation assay.Results: SGLT2 inhibition attenuated the growth of thyroid cancer cells in vitro and in vivo. Canagliflozin inhibited glucose uptake, glycolysis and AKT/mTOR signaling activation, and increased AMPK activation in thyroid cancer cell. Furthermore, canagliflozin inhibited G1/S phase transition and cyclin D1, cyclin D3, cyclin E1, cyclin E2, and E2F1 expression levels in thyroid cancer cell. In addition, canagliflozin increased apoptosis of thyroid cancer cell. Further investigation revealed that canagliflozin could increase γ-H2AX expression levels and DNA damage response signaling ATM/CHK2 activation. In thyroid cancer patients, SGLT2 was increased in thyroid cancer and positively related to cyclin D3.Conclusions: SGLT2 inhibition may limit glucose uptake resulting in energetic crisis, following oxidative stress mediated DNA damage and cell cycle arrest, which resulted to the increased cell apoptosis and decreased proliferation of thyroid cancer cells, suggesting a potential use for SGLT2 inhibitors as thyroid cancer therapeutics.

Background. Obesity has been considered as an important factor in the development and progression of chronic kidney diseases (CKD). Perirenal fat, which is surrounding the kidneys, has been reported to be unique in anatomy and biological functions. This study is aimed at assessing the relationship between perirenal fat thickness (PrFT) and estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes (T2DM).Methods. A total of 171 patients with T2DM were recruited in the study. The basic and clinical characteristics including sex, age, diabetes duration, body mass index (BMI), waist circumference (WC), visceral fat area (VFA), glycated hemoglobin (HbA1c), serum uric acid (UA), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were collected. PrFT was measured via ultrasound. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.Results. Patients were divided into three groups according to PrFT, and we found patients with higher PrFT had lower eGFR. PrFT was significantly correlated with eGFR in all patientsr=−0.181,P<0.05. Subgroup analysis by sex showed that PrFT still significantly and negatively related to eGFR in menr=−0.264,P<0.05, but not in women (r=−0.199,P=0.062). The association also existed in multivariate analysis after correction for the confounding factorsβ=−0.203,P=0.017.Conclusions. This study confirmed a negative independent relationship between PrFT and eGFR in patients with T2DM, especially in men, suggesting a possible role of perirenal fat in kidney dysfunction in T2DM patients.

As a common chronic metabolic disease, the development of diabetes mellitus (DM) may also be accompanied by liver damage and inflammatory disorders. Sitagliptin is an inhibitor of dipeptidyl peptidase-4 (DPP4, also known as CD26), which is clinically used for DM treatment. However, the mechanism of sitagliptin’s efficiency in liver diseases is largely unknown. In this study, mice suffering from streptozotocin (STZ) exhibit elevated liver DPP4 expression and activity, as well as inflammatory and chronic liver injury phenotype, whereas specifically inhibiting the activity of DPP4 in mouse liver tissues and hepatocytes by sitagliptin contributes to decreased cytokines, oxidative stress, cell apoptosis, and inflammation in STZ-induced diabetic mice. Moreover, sitagliptin reduced TNFα or LPS-induced cellular reactive oxygen species (ROS) level, cell apoptosis, and protein expression in the NFκB signaling pathway in HepG2 cells or primary mouse hepatocytes. Altogether, our study confirms that sitagliptin may protect liver tissue by alleviating ROS production and NFκB signaling activation, providing a putative mechanism for preventing the development of diabetic liver disease.

Introduction. Brachial–ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, has been demonstrated to be associated with type 2 diabetes mellitus (T2DM) and its vascular complications. This study was aimed at investigating the correlations of baPWV with both the presence and severity of diabetic retinopathy (DR) at baseline and at exploring the predictive role of baPWV in the new onset/progression of DR in the follow-up analysis. Methods. The prospective cohort study recruited 2,473 Chinese patients with T2DM, of whom 663 participants were finally included in the follow-up analysis. The presence and grading of DR were performed by the modified Early Treatment Diabetic Retinopathy Study. Uni- or multivariate linear and logistic regression models and Cox proportional-hazards regression analysis were conducted. Results. Of 2,473 patients with T2DM at baseline, 734 individuals were assessed to have DR and further categorized into 630 with non-sight-threatening DR (NSTDR) and 104 with STDR. In addition to the positive relationship between increased baPWV and the presence of DR, multinominal logistic regression analysis revealed that higher tertiles of baPWV were significantly related to the NSTDR (T2: (1.22, 2.15), , and T3: (1.86, 3.58), ) and STDR group (T3: (1.87, 8.02), ). During a follow-up (mean period of 16.4 months), 111 participants had new onset/progression of DR. The cox regressions showed that high baseline baPWV was correlated with increased risk of development/progression of DR ( , 95% CI (1.24, 4.03), , for T2 baPWV and , 95% CI (1.49, 5.64), , for T3 baPWV) after adjustments for multiple factors. Conclusions. Our results demonstrated that baseline baPWV might be an independent predictor in new onset/worsening of DR, suggesting that increased arterial stiffness might be involved in the development of DR. Follow-up studies with a longer duration are needed.

Background: Atherosclerosis is a common complication in patients with type 2 diabetes (T2DM). Multiple factors are involved in the development and progress of atherosclerosis. We evaluated the association of weekly sedentary time (WST) with carotid plaque formation.Methods: After data cleaning, a total of 26 664 participants with T2DM from 10 National Metabolic Management Centers (MMCs) from June 2017 to April 2021 were enrolled. Self‐reported lifestyle data including WST, sleeping time, smoking and drinking information, carotid artery ultrasound, and biochemical parameters were obtained. The independent association of carotid plaue with sedentary and other lifestyle behaviors was evaluated using multivariable logistic regression models, and odds ratio (OR) with 95% confidence interval (CI) were reported. Moreover, stratified analysis was conducted to demonstrate the influence of confounding factors.Results: The mean (SD) age of the participants was 54.0 (11.6) years, and the median (interquartile range) WST was 35.0 (21.0, 42.0) h. Comparing with participants in the first tertile of WST, those in the second or third tertile of WST were younger and with a shorter duration of diabetes. There were positive associations between longer sedentary time and odds of artery plaque after adjustment, with corresponding ORs in the second and third tertile were 1.40 (95% CI: 1.31–1.50) and 1.67 (95% CI: 1.56–1.79), respectively. However, the effect of WST on plaque in patients aged 18–40 years old had no statistical significance; the p value in the third tertile was 0.163.Conclusions: In summary, higher WST appears to be associated with higher prevalence of carotid plaque in patients with T2DM, especially in aged populations.