Effects of community family doctors-led intervention for self-management and medication adherence in type 2 diabetes mellitus patients: study protocol of a cluster randomised controlled trial.

INTRODUCTION: The management of diabetes has become a critical public health issue in China. The development of community-based type 2 diabetes management in China has not yet reached an ideal state, and the most suitable management methods for diabetic patients are still being explored. Few studies have used community-based family doctors to perform interventions of appropriate intensity. This protocol describes a planned randomised controlled trial to evaluate the effectiveness of a family doctor-led intervention model for diabetes self-management and medication adherence in type 2 diabetes mellitus patients. METHODS AND ANALYSIS: This is a Standard Protocol Items: Recommendations for Interventional Trials-compliant cluster randomised controlled trial. The study will be conducted at four CHCs (community health centers). The control group will receive conventional medical services and health education. The intervention group will receive an intervention led by community family doctors based on the conventional medical services and health education. It will include five parts: usual care, a medication reminder, a 4-week plan, a weekly phone interview and a monthly interview. The primary outcomes are changes in fasting blood glucose, glycosylated haemoglobin, self-management knowledge and behaviour, and medication adherence from baseline to the 3rd and 6th months. The secondary outcome is the proportion of people whose blood sugar and glycosylated haemoglobin are under control in the 3rd and 6th months. ETHICS AND DISSEMINATION: The study proposal was approved by the Biomedical Ethics Committee of the Medical Department of Xi'an Jiaotong University (no. 2021-1371). The findings will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR2100051685.

Dihydrotestosterone regulates oxidative stress and immunosuppressive cytokines in a female BALB/c mouse model of Graves' disease.

Background: Graves' disease (GD) is an autoimmune disease that affects more women than men. In our previous study, a potent bioactive androgen, 5α-dihydrotestosterone (DHT) showed a protective effect against GD in female BALB/c mice. Evidence indicates that abnormal oxidative stress and immunosuppressive cytokines (TGF-ß, IL-35) play critical roles in the pathogenesis and development of GD. The purpose of this research is to measure these cytokines and oxidative stress markers to explore potential protective mechanisms of DHT in a BALB/c mouse model of GD. Methods: GD was induced in female BALB/c mice by intramuscular injection of an adenovirus expressing the A-subunit of the TSH receptor (Ad-TSHR289). DHT or a matching placebo was injected every 3 days. Mice were sacrificed four weeks after the third virus immunization to obtain blood, thyroid and spleen for further analysis. Results: Thyroid hormones were significantly reduced in DHT treated GD mice. In addition, DHT attenuated thyroid oxidative injuries in GD mice, as shown by decreased total antioxidation capability (TAOC), superoxide dismutase (SOD) and the level of malondialdehyde (MDA). The levels of immunosuppressive cytokines (TGF-ß, IL-35) in DHT group were significant higher compared with the GD group. Conclusions: The results demonstrated that DHT could reduce the severity of GD in female BALB/c mice by regulating oxidative stress. The upregulation of immunosuppressive cytokines might be another important protective mechanism.

The Influence of Dihydrotestosterone on the Development of Graves' Disease in Female BALB/c Mice.

BACKGROUND: Graves' disease (GD) is a common organ-specific autoimmune disease characterized by hyperthyroidism that has significant sex differences in prevalence and clinical expressions. Abnormal cytokine production and T cell activation may result in various manifestations of GD. Studies have shown that androgen treatment can provide protection against autoimmune diseases, but the effects of androgen treatment on GD are still unknown. Therefore, this study investigated whether a potent bioactive androgen, 5α-dihydrotestosterone (DHT), could be of benefit in a BALB/c mouse model of GD. The aims of this study were to investigate (i) whether DHT pretreatment inhibits autoimmune responses, and (ii) the mechanism of immune protection of DHT in GD. METHODS: Female BALB/c mice were immunized three times with an adenovirus expressing the human thyrotropin receptor (TSHR) A-subunit (Ad-TSHR289). Three doses (1.5, 5, and 15 mg) of DHT or a matching placebo were implanted a week before the first immunization. Four weeks after the third immunization, mice were sacrificed, and blood, the spleen, and the thyroid were removed for further analysis. RESULTS: After DHT treatment, thyroid hormones were dramatically reduced compared with placebo. In addition, a remarkable reduction in interferon-γ and interleukin-2 production was observed in DHT-pretreated mice. CONCLUSIONS: DHT can alleviate the severity of GD by downregulating pro-autoimmune T helper 1 cells in female BALB/c mice. The protective influence was more noticeable with 5 mg and 15 mg doses of DHT.

A second course of antithyroid drug therapy for recurrent Graves' disease: an experience in endocrine practice.

OBJECTIVE: There are scarce reports regarding the prognosis of a second course of antithyroid drug (ATD) therapy on recurrent Graves' disease (GD). The aim of this study was to assess the long-term remission rate after a second ATD therapy and verify significant clinical predictors of a remission. DESIGN: A prospective randomized clinical trial with long-term follow-up was conducted to evaluate the effects of a second course of ATD therapy. METHODS: A total of 128 recurrent GD patients who had finished a first regular ATD therapy were enrolled in this study, and prescribed methimazole (MMI) treatment with titration regimen. The patients were randomly assigned to two groups when the drug doses were reduced to 2.5 mg daily (qd). Group 1 was discontinued with 2.5 mg qd after about 5 months. Group 2 was continuously reduced to 2.5 mg every other day (qod) after 5 months and then discontinued with 2.5 mg qod after about a further 5 months. The patients were followed for 48 months after drug withdrawal. RESULTS: Of the total number of patients, 97 cases (75.78%) achieved permanent remission at the end of follow-up, with the recurrence of 31 cases (24.22%). The remission rate of group 2 (84.62%) was significantly higher than that of group 1 (66.67%) (P=0.024). Cox regression showed that the hazard ratio for recurrence decreased under a high or high normal TSH level at drug withdrawal. CONCLUSION: A second course of ATD therapy can bring about a satisfying long-term remission on recurrent GD. The drug dose of 2.5 mg qod and a high or high normal TSH level at drug withdrawal may increase the likelihood of permanent remission.