Comparison of the therapeutic effects of 15 mg and 30 mg initial daily prednisolone doses in patients with subacute thyroiditis: a multicenter, randomized, open-label, parallel-controlled trial.

INTRODUCTION: Current guidelines recommendations for the initial dose of prednisolone (PSL) in the treatment of subacute thyroiditis (SAT) are based on low-quality studies. We designed a randomized controlled trial (RCT) to compare the efficacy and safety of using a low initial dose of PSL with a standard initial dose of PSL in SAT patients. PATIENTS AND METHODS: This open-label RCT was conducted at five hospitals in China from June 2019 to January 2022. SAT patients with moderate-to-severe pain or a poor response to non-steroidal anti-inflammatory drugs (NSAIDs) were randomly assigned in a 1:1 ratio to the experimental and control groups. The initial dose of PSL was 15 mg/d in the experimental group and 30 mg/d in the control group. The primary outcome was the total duration of PSL treatment, with non-inferiority prespecified with a margin of 7 days. Clinical trial registration number: ChiCTR1900023884. RESULTS: The full analysis set included 60 patients (30 in each group). The mean duration of PSL treatment in the experimental and control group was 34.62 ± 14.12 and 41.18 ± 16.89 days, respectively, meeting the non-inferiority criterion (pnon-inferiority = 0.0006). The total dose of PSL used in the experimental group was lower than in the control groups (330 vs 595 mg, p < 0.0001). There were no differences in the mean time to pain relief and complete resolution, the occurrence of recurrence, hypothyroidism, or adverse events between the groups. CONCLUSIONS: The initial dose of 15 mg/d of PSL was not inferior to the dose of 30 mg/d in terms of efficacy and showed a similar safety profile. A low initial dose of PSL could be recommended for Chinese adult SAT patients who have a suboptimal response using NSAIDs or experience moderate-to-severe pain.KEY MESSAGESLow initial dose (15 mg/d) of prednisolone was non-inferior to the standard initial dose of prednisolone (30 mg/d) in treatment duration, time to pain relief, or the prevalence of hypothyroidism, recurrence, and adverse reactions in the treatment of subacute thyroiditis.Patients with subacute thyroiditis administered a low initial dose of prednisolone had a lower total dose of prednisolone compared to those receiving the standard dose of prednisolone.

Serum 25-hydroxyvitamin D level is associated with short-term glycemic variability metrics derived from continuous glucose monitoring in T2DM.

This study aims to investigate the association between 25-hydroxyvitamin D (25OHD) and continuous glucose monitoring-assessed short-term glycemic variability (GV) and HbA1c among patients with type 2 diabetes mellitus (T2DM). We conducted a cross-sectional study recruiting 325 patients. The association between 25OHD and GV metrics (mean amplitude of glycemic excursions [MAGE], coefficient of variation [CV], standard deviation of sensor glucose [SD], and TIR) and HbA1c were analyzed using multivariable linear and logistic regression analyses. The 25OHD level and GV metrics showed significant differences among HbA1c groups (P < 0.01). CV, MAGE, SD and HbA1c decreased, and TIR increased with ascending 25OHD tertiles (P < 0.05). Serum 25OHD was inversely associated with CV (ß = - 0.211 [- 0.350 to - 0.071], P < 0.01) and HbA1c (ß = - 0.061 [- 0.114 to - 0.031], P < 0.01), and further multivariable analyses confirmed these results (P < 0.05). However, no association of HbA1c and 25OHD was found with the highest tertile of CV. These findings revealed that increased GV and HbA1c were both associated with lower 25OHD, and the relationship between HbA1c and 25OHD was attenuated with higher glucose CV in T2DM. Taken together, the analyses suggest that increasing vitamin D status has effects on improvements in long-term glycemic control and low glycemic variability.

Insulin-like growth factor binding protein-1 and insulin in polycystic ovary syndrome: a systematic review and meta-analysis.

Background: Insulin-like growth factor binding protein-1 (IGFBP-1) is considered a decline in polycystic ovary syndrome (PCOS), but it remains controversial that whether such reduction is attributed to obesity. Aims: This systematic review aims to explore whether IGFBP-1 is reduced in PCOS, and whether such reduction is associated with obesity. Results: Our pooled study included 12 studies with a total of 450 participants. IGFBP-1 levels in PCOS were significantly lower than that in non-PCOS (SMD (95%CI)=-0.49(-0.89, -0.09), P=0.02). No significant difference in IGFBP-1 levels between patients with or without PCOS classified by BMI. Whilst, stratification by PCOS status revealed a significant decrease in IGFBP-1 in overweight (SMD (95%CI)=-0.92(-1.46, -0.37), P=0.001). When comparing fasting insulin in the same way, PCOS patients had significantly elevated fasting insulin level but not statistically declined IGFBP-1 after classified by BMI. Conclusion: This meta-analysis provides evidence that the decrease of IGFBP-1 in PCOS was more strongly influenced by comorbid obesity than by PCOS itself. Additionally, contrast to previous findings that insulin significantly suppresses IGFBP-1, our results suggested that the suppression of PCOS-related hyperinsulinemia on IGFBP-1 seemed diminished. Overall, our work may provide a novel perspective on the mechanism between insulin and IGFBP-1 underlying PCOS development.

Tunicamycin promotes metastasis through upregulating endoplasmic reticulum stress induced GRP78 expression in thyroid carcinoma.

BACKGROUND: Thyroid cancer (TC) is the most common type of endocrine malignancy and its incidence is increasing over years. Conventional surgery, radiotherapy and chemotherapy are difficult to improve the significant effects of it due to aggression and metastasis of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), and these are regarded as the most malignant types of TC. Glucose-regulated protein (GRP78) is the key molecule of tumor growth, apoptosis and metastasis. However, the underlying mechanisms of GRP78 in TC still require discussion. This study aimed to explore the role of GRP78 and its potential mechanism in TC. RESULTS: GRP78 expression was increased in TC tissues when compared with adjacent normal tissues. Besides, down-regulation of GRP78 significantly inhibited the metastatic and proliferative ability of ATC cells in in vitro studies. In addition, tunicamycin-induced ER stress up-regulated the expression of GRP78, PERK and XBP1 as well as reversed the metastatic ability of GRP78 in ATC cells. Bioinformatics and statistical analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for RNA-sequencing data with regard to si-GRP78 and si-control showed that GRP78 might regulate the ability of metastasis through extracellular matrix (ECM) remodeling in ATC cells, as well as the expression of ECM components such as COL1A1 and MMP13, which were highly relevant to ATC cells. The analysis of GEPIA database confirmed that high genomic amplification of MMP13 and COL1A1 in TC tissues showed correlation with TNM stage. Further western blotting analysis showed that MMP13 might be the target of GRP78 in ATC cells and ER stress could activate the expression of MMP13 that is suppressed by GRP78 depletion. CONCLUSIONS: GRP78 acts as an important regulator of metastasis under ER stress. In addition, the function of GRP78 might be mediated by ECM remodeling in ATC cells, implicating it as a therapeutic target in TC.

Comparison of the therapeutic effects of 15 mg and 30 mg initial dosage of prednisolone daily in patients with subacute thyroiditis: protocol for a multicenter, randomized, open, parallel control study.

BACKGROUND: Subacute thyroiditis (SAT) is the most common cause of thyroid pain. Several clinical guidelines recommend that patients who fail to respond to full doses of non-steroidal anti-inflammatory drugs (NSAIDs) should be treated instead with oral corticosteroid therapy. However, albeit strong recommendations, the treatment protocol is based on low-quality evidence and high-quality clinical trials are lacking with respect to the optimal initiation dosage and usage of corticosteroid. We aimed to evaluate whether 15 mg/day of prednisolone (PSL) as the initial dosage could provide non-inferiority effectiveness but with lower risk and more safety compared with 30 mg/day of PSL as the initial dosage. METHODS/DESIGN: This is a multicenter, open-label, randomized, parallel trial that will be conducted at five academic hospitals in China. A total of 90 adult patients diagnosed with SAT who present moderate to severe pain or fail to respond to full doses of NSAIDs will be randomly assigned with a 1:1 ratio to the low initial PSL dosage group (15 mg daily) and standard initial PSL dosage group (30 mg daily). The primary endpoint is the time period (days) required for PSL treatment (including PSL treatment for recurrence). DISCUSSION: Our randomized controlled trial will try to determine the optimal protocol in the treatment of SAT by providing high-quality evidence. TRIALS REGISTRATION: Chinese Clinical Trial Register, ChiCTR1900023884. Registered on 15 June 2019.

Influencing factors of glycemic variability in hospitalized type 2 diabetes patients with insulin therapy: A Strobe-compliant article.

Previous studies have shown that glucose fluctuation is closely related to oxidative stress and diabetic complications. However, only few studies have evaluated the influencing factors of glycemic variability (GV) in type 2 diabetes (T2D) patients so far.This was a cross-sectional study design. A total of 366 cases of hospitalized patients with T2D using insulin therapy, whom received continuous glucose monitoring from January 2014 to December 2016, were enrolled for this study. The evaluation variables of GV included standard deviation of blood glucose, coefficient of variation (CV%), mean amplitude of glycemic excursion, and absolute means of daily differences.In 366 T2D patients with insulin therapy, 148 were used multiple daily injections (MDI) insulin regimen; 144 were on premixed insulin injection; and 74 were treated with continuous subcutaneous insulin injection. Compared with MDI insulin regimen, patients on premixed insulin injection have less insulin dose per day, lower mean blood glucose, and better glycated hemoglobin (HbA1c) (all P <.05). Generalized linear model showed that family history of diabetes, duration of diabetes, higher HbA1c, and higher level of aspartate aminotransferase and high-density lipoprotein cholesterol were positively associated with GV parameters. Otherwise, serum levels of C-peptide, premixed insulin injection, history of cardiovascular disease, and serum concentration of uric acid were inversely associated with GV parameters.Dysfunction of pancreatic ß-cell and better insulin sensitivity were independent contributors to the fluctuation of blood glucose. Moreover, premixed insulin therapy may obtain better glucose control and lower within-day and day-to-day glucose variability for Chinese T2D patients with insulin therapy.

[Effects of telmisartan on the expression of adiponectin and its receptors in testes of type 1 diabetic rats].

OBJECTIVE: To explore the effects of telmisartan on the expressions of adiponectin and adiponectin receptor and its signal transduction pathway AMP-activated protein kinase (AMPK), Akt/endothelial nitric oxide synthase (Akt/e-NOS/NO) and examine the possible protective mechanisms of telmisartan in testis of type 1 diabetic rats. METHODS: A total of 27 male Sprague-Dawley rats were randomly divided into normal control (NC, n=8) group and diabetic model (n=19) group. Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ). And 16 established diabetic rats were randomly divided into diabetic control (DM, n=8) and diabetic treated with telmisartan (DT, n=8) groups. Group DT received a lavage of telmisartan while groups NC and DM had an equal volume of normal saline by gavage. At the end of 8-week of telmisartan treatment, the animals were sacrificed after harvesting of blood samples. Bilateral testes were extracted and epididymis was minced for preparing sperm suspension. Blood samples were used to detect the related parameters. Some tresticular tissues were fixed in neutral 40% formaldehyde solution and processed for histological analysis. And the remaining testicular tissues were immediately placed into liquid nitrogen and then stored in a -70 °C refrigerator until analyses. The levels of insulin and sex hormone were detected by radioimmunoassay. The levels of adiponectin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assayed by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of testicular adiponectin and its receptor was assessed by real-time fluorescent quantitative polymerase chain reaction (PCR). The protein expressions of testicular adiponectin, adiponectin receptor, AMPK, P-AMPK, AKT, P-AKT and e-NOS were analyzed by Western blot. RESULTS: There was significant pathological changes in testes in group DM than that in group NC. The levels of P-AKT/AKT, e-NOS and NO were significantly increased in group DM than those in group NC [(1.54 ± 0.27) vs (1.00 ± 0.00), (1.56 ± 0.26) vs (1.00 ± 0.00), (1.75 ± 0.28) vs (1.08 ± 0.02) µmol/g, all P<0.05]. The levels of serum adiponectin,testicular adiponectin and its receptor 1, and the ratio of P-AMPK to AMPK significantly decreased in group DM than that in group NC [(622.46 ± 95.86) vs (2 022.07 ± 51.13)ng/ml, (0.66 ± 0.09) vs (1.00 ± 0.00), (0.68 ± 0.05) vs (1.00 ± 0.00), (0.34 ± 0.11) vs (1.00 ± 0.00), all P<0.05]. There was no significant difference in the expression of adiponectin receptor 2 between group DM and NC [(1.02 ± 0.13) vs (1.00 ± 0.00), P>0.05]. After 8-week telmisartan treatment, the pathological changes of testes became alleviated in diabetic rats. The levels of P-AKT/AKT, e-NOS and NO significantly decreased in group DT than those in group DM [(1.24 ± 0.39) vs (1.54 ± 0.27), (1.16 ± 0.47) vs (1.56 ± 0.26), (1.35 ± 0.30) vs (1.75 ± 0.28) µmol/g, all P<0.05]. The serum and testicular levels of adiponectin and testicular adiponectin receptor 1 significantly increased in group DT than those in group DM [(1 051.55 ± 102.55) vs (622.46 ± 95.86), (0.84 ± 0.09) vs (0.66 ± 0.09), (0.80 ± 0.07) vs (0.68 ± 0.05), all P<0.05]. No significant difference existed in the ratio of P-AMPK to AMPK in testes or the expression of adiponectin receptor 2 between group DM and NC [(0.65 ± 0.52) vs (0.34 ± 0.11), (1.02 ± 0.15) vs (1.02 ± 0.13), all P>0.05]. CONCLUSION: Telmisartan may reduce the injury degree of testes and play protective roles in testicular tissues in diabetic rats by regulating the expressions of adiponectin, adiponectin receptor and the signal pathways mediated by adiponectin receptor.