Background Clinical investigations have found that there was a close association between T2DM and adverse cardiovascular events, with possible mechanisms included inflammation, apoptosis, and lipid metabolism disorders. High serum GDF-15 concentration and the apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) are involved in the above-mentioned mechanisms and are thought to be related to the occurrence of adverse cardiovascular events. However, it remains unclear whether circulating GDF-15 levels and the ApoB/ApoA1 ratio are related to T2DM patients with CAD. Methods T2DM patients with or without CAD were eligible for this study. According to the inclusion and exclusion criteria, 502 T2DM patients were enrolled between January 2021 and December 2021 and were then divided into T2DM group (n = 249) and CAD group (n = 253). The ApoB, ApoA1 and GDF-15 concentrations were measured at hospital admission and the ApoB/ApoA1 ratio was then calculated. Results Compared with T2DM group, serum GDF-15 levels and ApoB/ApoA1 ratio increased in CAD group. Furthermore, a positive relationship between the occurrence of CAD in diabetic population and circulating GDF-15 concentrations and ApoB/ApoA1 ratio was observed in logistic regression analysis (p < 0.01). Restrictive cubic spline analysis after adjusted for multiple risky variables showed that serum GDF-15 or ApoB/ApoA1 ratio correlated positively with CAD. Conclusions Circulating GDF-15 levels and serum ApoB/ApoA1 ratio vary in CAD group and T2DM group. ApoB/ApoA1 and GDF-15 may be helpful for predicting the occurrence of CAD in patients with T2DM.
Aims Epidemiological studies consistently show that decreases in serum testosterone level are observed more frequently in men with type 2 diabetes mellitus (T2DM), while clinical investigations have demonstrated that an increased level of circulating growth differentiation factor‐15 (GDF‐15) are also related closely to T2DM. The aim of this study was to examine the potential relationship between serum GDF‐15 levels and hypogonadism in Chinese male patients with T2DM. Materials and Methods A total of 305 T2DM men were recruited between July 2020 and August 2021. GDF‐15 and total testosterone concentrations were quantified by an enzyme‐linked immunosorbent assay and LC/MS mass spectrometry, respectively. Multiple linear regression analysis, logistic regression, and restricted cubic splined models were used to examine the correlation between GDF‐15 levels and hypogonadism in these patients. Results When compared with T2DM patients without hypogonadism circulating GDF‐15 levels were significantly higher in the hypogonadism group [1081.83 (746.79,1539.94) versus 779.49 (548.46,1001.27), p < 0.001] and were associated positively with hypogonadism in unadjusted and fully adjusted multivariate regression models (p < 0.01). The fully adjusted regression coefficients with 95% confidence intervals for circulating GDF‐15 and testosterone deficiency were −1.795 (−2.929, −0.661). Serum GDF‐15 levels were also associated positively with testosterone deficiency in each logistic regression model (p < 0.05), while after adjustment for all risk factors, the same findings were obtained in the restricted cubic splined models (p < 0.01). Conclusions In hypogonadal men with T2DM, an elevated serum GDF‐15 level is associated negatively with serum testosterone concentration. GDF‐15 may be a novel cytokine related to T2DM men with hypogonadism.
Background High serum NEFA and GDF-15 are risk factors for CAD and have been linked to detrimental cardiovascular events. It has been hypothesized that hyperuricemia causes CAD via the oxidative metabolism and inflammation. The current study sought to clarify the relationship between serum GDF-15/NEFA and CAD in individuals with hyperuricemia. Methods Blood samples collected from 350 male patients with hyperuricemia(191 patients without CAD and 159 patients with CAD, serum UA > 420 μmol/L) to measure serum GDF-15 and NEFA concentrations with baseline parameters. Results Serum circulating GDF-15 concentrations(pg/dL) [8.48(6.67,12.73)] and NEFA levels(mmol/L) [0.45(0.32,0.60)] were higher in hyperuricemia patients with CAD. Logistic regression analysis revealed that the OR (95% CI) for CAD were 10.476 (4.158, 26.391) and 11.244 (4.740, 26.669) in quartile 4 (highest) respectively. The AUC of the combined serum GDF-15 and NEFA was 0.813 (0.767,0.858) as a predictor of whether CAD occurred in male with hyperuricemia. Conclusions Circulating GDF-15 and NEFA levels correlated positively with CAD in male patients with hyperuricemia and measurements may be a useful clinical adjunct.
BackgroundFibroblast growth factor 21 increased in population with type 2 diabetes mellitus (T2DM), while serum total testosterone often decreased in men with T2DM. This study aimed to investigate the relationship between the prevalence of coronary artery disease (CAD) and circulating FGF21 concentrations and serum testosterone in T2DM men.Methods490 men with T2DM from January 2021 to December 2021 were recruited from the Renmin Hospital of Wuhan University, and they were divided into CAD group (n=248) and control group (n=242). FGF21 were determined based on ELISA principle and serum total testosterone was measured in a liquid chromatography mass spectrometer LC/MS-8050 (Shimadzu, Japan). Logistic and restricted cubic spline analyses were performed to examine the association between the prevalence of CAD and circulating FGF21 concentrations and serum testosterone in T2DM men. The receiver operating curve (ROC) analysis was used to explore the predictive performance.ResultsCirculating FGF21 levels were higher in T2DM men with CAD compared with those without CAD [214.63 (121.82, 348.64) pg/ml vs 166.55 (94.81,254.48) pg/ml, p<0.001], while serum total testosterone was lower [3.08 ± 0.07 ng/ml vs 3.76 ± 0.09 ng/ml, p<0.001]. The fully adjusted odds ratio (OR) and 95% confidence intervals (95%CI) was 2.956(1.409,6.201) for those in quartile 4 of FGF21 versus quartile 1 and the fully adjusted OR (95%CI) was 0.346(0.174,0.686) for those in quartile 4 of testosterone versus quartile 1. The receiver operating curve (ROC) analysis showed that the area under the curve (AUC) of combination of FGF21 and testosterone for predicting the occurrence of CAD in men with T2DM was 0.702 (95% CI: 0.667-0.741).ConclusionCirculating FGF21 levels were positively associated with CAD in men with T2DM, whereas serum total testosterone levels showed an inverse correlation with CAD in diabetic men.
Major depressive disorder (MDD) is a worldwide life-threatening disorder with high incidence and high mortality. Besides, the neurotrophic effects of estrogen have been demonstrated in many neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's disease (PD). However, the mechanistic interplay between depression, neuroinflammation and estrogen remain unclear. Here, this study investigated the effect of E2 on neuroinflammation and depressive-like behaviors induced by ovariectomy (OVX), as well as the underlying mechanism. We found the anti-depressant effect of E2 through behavioral experiments and verified the anti-apoptotic effect of E2 on the depressive hippocampus in mice, and finally we showed that E2 alleviated inflammatory response and reversed depressive-like behaviors by inhibiting gp130/JAK1/STAT3 signaling pathway via combining with estrogen receptor-β (ER-β) in vivo and vitro. These results suggested that E2 possesses potent anti-depressive action, which might be mediated via inhibition of neuroinflammation and apoptosis impairment by promoting the interaction between gp130 and ER-β.
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