Association Between Sensitivity to Thyroid Hormone Indices and Diabetic Retinopathy in Euthyroid Patients with Type 2 Diabetes Mellitus.

Objective: Normal thyroid hormone (TH) levels and their relation to microvascular complications in patients with type 2 diabetes mellitus (T2DM) have been studied. However, the relationship between TH sensitivity and diabetic retinopathy (DR) remains unclear. Thus, this study aimed to investigate the relationship between TH sensitivity and the risk of DR in euthyroid T2DM patients. Methods: This retrospective study analyzed 422 T2DM patients and calculated their sensitivity to TH indices. Multivariable logistic regression, generalized additive model, and subgroup analysis were performed to examine the association between sensitivity to TH indices and DR risk. Results: After adjusting for covariates, the binary logistic regression model showed no statistically significant association between the sensitivity of TH indices and the risk of DR in euthyroid T2DM patients. However, a non-linear relationship was found between sensitivity to TH indices (thyroid-stimulating hormone index, thyroid feedback quantile index [TFQI]) and the risk of DR in the crude model; TFQI and DR in the adjusted model. The inflection point of the TFQI was 0.23. The effect size (odds ratio) on the left and right of the inflection point were 3.19 (95% confidence interval [CI]: 1.24 to 8.17 p=0.02) and 0.11 (95% CI: 0.01, 0.93 p=0.04), respectively. Moreover, this relationship was maintained by men stratified by sex. In euthyroid patients with T2DM, an approximate inverted U-shaped relationship and a threshold effect were demonstrated between TH index sensitivity and DR risk with sex differences. This study provided an in-depth understanding of the relationship between thyroid function and DR, which has important clinical implications for risk stratification and individual prediction.

Relationship between microRNA expression and inflammatory factors in patients with both type 2 diabetes mellitus and periodontal disease.

OBJECTIVE: To investigate the expression of single-stranded microRNAs (miRNAs) in serum and gingival crevicular fluid of patients with type 2 diabetes mellitus (T2DM) complicated by periodontal disease and its correlation with inflammatory factors. METHODS: Twenty-six periodontitis patients without diabetes mellitus (periodontal group), 24 patients with T2DM (T2DM group), 22 patients with both T2DM and periodontal disease (comorbid group), and 25 healthy individuals without a history of periodontal disease (healthy group) were recruited respectively. Serum and gingival crevicular fluid specimens were collected to detect the expression levels of miRNAs and inflammatory factors including serum tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and transforming growth factor-ß (TGF-ß), and their correlations were also investigated. RESULTS: Eleven miRNAs were detected in the gingival crevicular tissue of all subjects. The expression of miR-223 and miR-200b in serum and gingival crevicular fluid was elevated higher in the comorbid group than in the other three groups (P<0.05), and their expressions in gingival crevicular fluid contributed to the differential diagnosis of periodontal disease from diabetes mellitus comorbid with periodontal disease (P<0.05). Gingival crevicular fluid miR-223 expression was positively associated with TNF-α, clinical attachment loss (CAL), and probing pocket depth (PPD) in the periodontal group, while negatively associated with IL-10 (P<0.05), and so was gingival crevicular fluid miR-200b expression with TNF-α, CAL, and PPD (P<0.05). In the comorbid group, gingival crevicular fluid miR-223 expression showed a positive correlation with TNF-α, CAL, and PPD (P<0.05), and so did gingival crevicular fluid miR-200b expression with TNF-α, CAL, and PPD (P<0.05). CONCLUSIONS: Our findings indicate a close link between the levels of miR-223 and miR-200b in serum and gingival crevicular fluid and susceptibility to T2DM as well as the pathogenesis of periodontal disease.

Correlation between salivary HBD-2 and LL-37 expression levels with blood glucose and periodontal status in patients with type 2 diabetes mellitus.

OBJECTIVE: To examine the correlation between salivary human ß defensin-2 (HBD-2) and LL-37 expression levels and blood glucose in relationship to periodontal status in patients with type 2 diabetes mellitus (T2DM). METHODS: The trial is available at: https://clinicaltrials.gov/ with ClinicalTrials.gov Identifier: NCT03512675. A total of 89 patients with T2DM with chronic periodontitis (CP) enrolled in our hospital from January 2020 to December 2020 were selected. According to the degree of glycemic control and CP, the patients were randomly divided into four groups, namely the good glycemic control and mild CP group (n=26), good glycemic control with moderate to severe CP group (n=24), poor glycemic control with mild CP group (n=21), and poor glycemic control with moderate to severe CP group (n=18). The periodontal clinical parameters, blood glucose indicators, and saliva HBD-2 and LL-37 expression levels were determined. RESULTS: The expression levels of HBD-2 and LL-37 in the saliva of T2DM patients with moderate to severe CP and poor blood sugar control were significantly increased (P<0.05). Saliva HBD-2 and LL-37 levels were positively correlated with probing depth, clinical attachment loss, plaque index, and glycosylated hemoglobin. There was a synergistic interaction between blood glucose, periodontal status, and saliva HBD-2, LL-37 levels (P<0.05). CONCLUSION: There is a positively correlated relationship between blood glucose and periodontal status with salivary HBD-2 and LL-37 levels.

Chemerin/CMKLR1 Axis Promotes the Progression of Proliferative Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes, and the levels of chemerin were associated with the severity of DR. However, there is no research on chemerin in the development of proliferative diabetic retinopathy (PDR). Therefore, our study aimed to explore the relationship between chemerin and PDR. METHODS: The levels of chemerin/chemokine-like receptor (CMKLR1), proinflammatory cytokines, and vascular endothelial growth factor (VEGF) in 90 cases of PDR and nonproliferative diabetic retinopathy (NPDR) patients and in high glucose (HG) stimulated human retinal pigment epithelium cells (ARPE-19) were evaluated by ELISA. Moreover, chemerin was added into HG-induced ARPE-19 cells to assess its effect on proinflammatory cytokines and VEGF. RESULTS: The levels of chemerin/CMKLR1 were higher in PDR patients than NPDR ones, and chemerin was positively correlated with CMKLR1 in PDR patients. Compared to NPDR, the secretions of proinflammatory cytokines and VEGF were increased in PDR patients and positively correlated with chemerin/CMKLR1. Additionally, chemerin activated CMKLR1 and aggravated HG-induced cell injury, inflammatory responses, and VEGF expressions in ARPE-19 cells. CONCLUSION: Our study demonstrated that chemerin/CMKLR1 axis aggravated the progression of PDR, which suggested that inhibition of chemerin might serve as a new therapeutic approach to treat PDR.

Correlation between salivary developmental endothelial locus-1, interleukin 17 expression level and severity of periodontal disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To investigate the correlation of the salivary expression levels of developmental endothelial locus-1 (Del-1) and interleukin 17 (IL-17) with the severity of periodontal disease in patients with type 2 diabetes mellitus (T2DM). METHODS: Fifty-seven patients with T2DM and fifty-seven patients with T2DM complicated with chronic periodontitis (CP) admitted to our hospital from March 2020 to March 2021 were enrolled as the research objects and assigned to the T2DM group and T2DM+CP group respectively. Additionally, 57 healthy controls from the hospital physical examination center during the same period were included as the healthy controls. General information of all the enrolled participants was collected to measure the levels of glycated hemoglobin (HbA1c), salivary inflammatory factors, and salivary Del-1 and IL-17, as well as homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: HbA1c in the T2DM group and T2DM+CP group was significantly higher than that in the healthy control group. Gingival index (GI), plaque index (PI), and probing depth (PD) were significantly higher in case groups than those in the health group. Compared with the healthy control group, salivary IL-17 expression level increased remarkably in the T2DM+CP group and T2DM group, with a higher level observed in the T2DM+CP group (P<0.05). The T2DM+CP group presented significantly higher levels of salivary tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) than the other two groups (P<0.05). Compared with the healthy control group, HOMA-IR and salivary Del-1 declined evidently in the T2DM+CP group and T2DM group, and the lowest values were observed in the T2DM+CP group (P<0.05). Salivary Del-1 and HbA1c were independent risk factors for CP in T2DM patients (P<0.05). CONCLUSION: Salivary Del-1 was downregulated and IL-17 was up-regulated in T2DM patients complicated with CP, indicating their correlation with the occurrence of CP in T2DM patients.