Xiao-jun Zhou, Lin Ding, Jia-xin Liu, Le-qun Su, Jian-jun Dong and Lin Liao
To investigate the difference in the efficacy among dipeptidyl peptidase-4 (DPP-4) inhibitors in Chinese adults with newly diagnosed diabetes.
Materials and methods
In a multicenter, randomized study, we enrolled adults who were either treatment naive or off prior anti-hyperglycemic therapy for at least 3 months. Eligible patients had hemoglobin A1c (HbA1c) concentrations of 6.5–9.5%. Three hundred patients had been randomly allocated to sitagliptin 100 mg, once daily; vildagliptin 50 mg, twice daily and saxagliptin 5 mg, once daily for 12 weeks. Patients and investigators were masked to treatment assignment. The primary endpoint was change from baseline in HbA1c at week 12. This study was completed and registered with ClinicalTrials.gov, number NCT 01703637.
Totally 277 patients were enrolled in the final analysis, and 93 patients received sitagliptin, 94 received vildagliptin and 90 received saxagliptin. Compared with baseline, adjusted mean differences in change from baseline HbA1c at week 12 were −0.50% (95% CI: −0.20 to −0.90), −0.65% (95% CI: −0.40 to −1.40), −0.70 (95% CI: −0.50 to −1.00) for sitagliptin, vildagliptin and saxagliptin group, respectively. The overall HbA1c-lowering effect was similar for all three selected DPP-4 inhibitors after adjustment for age and baseline HbA1c. Notably, in secondary outcome analysis, patients in vildagliptin group showed a significant decrease in total cholesterol levels, compared with participants in sitagliptin and saxagliptin groups. No significant between-group difference was shown in adverse events (AE).
The overall HbA1c-lowering effect and incidence of AE were similar for sitagliptin, vildagliptin and saxagliptin in Chinese adults with newly diagnosed diabetes.
Qiu-ming Yao, Bin Wang, Xiao-fei An, Jin-an Zhang and Liumei Ding
Type 2 diabetes is a risk factor for testosterone deficiency and impaired sex steroid status. Some studies also investigated the association of testosterone level with diabetes risk in men, but reported controversial findings. To clarify this issue, we conducted a systematic review and meta-analysis.
PubMed, EMBASE and Web of Science were searched for eligible cohort or nested case–control studies published up to August 15, 2017. Meta-analysis was used to calculate the pooled relative risk (RR) of type 2 diabetes associated with higher testosterone level.
Thirteen cohort or nested case–control studies with 16,709 participants were included. Meta-analysis showed that higher total testosterone level could significantly decrease the risk of type 2 diabetes in men (RR = 0.65; 95% CI 0.50–0.84; P = 0.001), and higher free testosterone level could also decrease the risk of type 2 diabetes in men (RR = 0.94; 95% CI 0.90–0.99; P = 0.014). After excluding two studies that did not calculate RRs by quartiles of testosterone levels, both higher total testosterone and free testosterone levels could decrease the risk of type 2 diabetes in men, and the pooled RRs were 0.62 (95% CI 0.51–0.76; P < 0.001) and 0.77 (95% CI 0.61–0.98; P = 0.03), respectively.
This meta-analysis suggests that higher testosterone level can significantly decrease the risk of type 2 diabetes in men. Therefore, combined with previous researches, the findings above suggest a reverse-causality scenario in the relation between testosterone deficiency and risk of type 2 diabetes in men.
Yun Hu, Na Li, Peng Jiang, Liang Cheng, Bo Ding, Xiao-Mei Liu, Ke He, Yun-Qing Zhu, Bing-li Liu, Xin Cao, Hong Zhou and Xiao-Ming Mao
Thyroid nodules are usually accompanied by elevated thyroglobulin (Tg) level and autoimmune thyroid diseases (AITDs). However, the relationship between Tg and AITDs is not fully understood. Dysfunction of regulatory T cells (Tregs) plays an important role in the development of AITDs. We aimed to evaluate the effects of Tg on the function of Tregs in patients with thyroid nodules.
Tg levels and the functions of Tregs in peripheral blood and thyroid tissues of patients with thyroid nodules from Nanjing First Hospital were evaluated. The effects of Tg on the function of Tregs from healthy donors were also assessed in vitro. The function of Tregs was defined as an inhibitory effect of Tregs on the effector T cell (CD4+ CD25− T cell) proliferation rate.
The level of Tg in peripheral blood correlated negatively with the inhibitory function of Tregs (R = 0.398, P = 0.03), and Tregs function declined significantly in the high Tg group (Tg >77 μg/L) compared with the normal Tg group (11.4 ± 3.9% vs 27.5 ± 3.5%, P < 0.05). Compared with peripheral blood, the function of Tregs in thyroid declined significantly (P < 0.01), but the proportion of FOXP3+ Tregs in thyroid increased (P < 0.01). High concentration of Tg (100 μg/mL) inhibited the function of Tregs and downregulated FOXP3, TGF-β and IL-10 mRNA expression in Tregs in vitro.
Elevated Tg level could impair the function of Tregs, which might increase the risk of AITDs in patient with thyroid nodules.
Jintao Hu, Qingbo Chen, Xiao Ding, Xin Zheng, Xuefeng Tang, Song Li and Hui Yang
Many cancer cells cannot survive without exogenous glutamine (Gln); however, cancer cells expressing glutamine synthetase (GS) do not have this restriction. Previous metabolomics studies have indicated that glutamine metabolism is altered during pituitary tumorigenesis. However, the main role of Gln in pituitary adenoma (PA) pathophysiology remains unknown. The aim of this study was to evaluate the expression of GS and the main role of Gln in human PAs.
We used cell proliferation assay and flow cytometry to assess the effect of Gln depletion on three different pituitary cell lines and human primary PA cells. We then investigated the expression level of Gln synthetase (GS) in 24 human PA samples. At last, we used LC-MS/MS to identify the differences in metabolites of PA cells after the blockage of both endogenous and exogenous Gln.
PA cell lines showed different sensitivities to Gln starvation, and the sensitivity is correlated with GS expression level. GS expressed in 21 out of the 24 human PA samples. Furthermore, a positive p53 and ki-67 index was correlated with a higher GS expression level (P < 0.05). Removal of both endogenous and exogenous Gln from GS-expressing PA cells resulted in blockage of nucleotide metabolism and cell cycle arrest.
Our data indicate that GS is needed for PA cells to undergo proliferation during Gln deprivation, and most human PA cells express GS and might have a negative response to exogenous Gln depletion. Moreover, Gln is mainly responsible for nucleotide metabolism in the proliferation of GS-expressing pituitary tumor cells.