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Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus and also has hepatoprotective effects. However, the role of liraglutide treatment on liver injury in a mouse model of type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ) and its underlying mechanisms remain to be elucidated. In the present study, diabetes was initiated in experimental animals by single-dose intraperitoneal inoculation of STZ. Forty female C57BL/6J mice were equally assigned into five groups: diabetic group, insulin+diabetic group, liraglutide+diabetic group, insulin+liraglutide+diabetic group, and control group for eight weeks. Diabetic mice exhibited a significantly elevated blood glucose level and decreased body weight, and morphological changes of increased steatosis and apoptosis were observed in the liver compared with the control. Furthermore, a significant increase in the levels of malondialdehyde and inflammatory markers such as tumor necrosis factor- α (TNF- α ), interleukin-6 (IL-6), and interleukin 1 β (IL-1 β ) and the proapoptotic proteins caspase-3 and Bax were observed in the livers of diabetic mice, together with marked increases in antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as antiapoptotic protein Bcl-2, all of which were significantly mitigated by treatment with liraglutide, insulin, and their combinations. Interestingly, liraglutide monotherapy showed better efficacy in ameliorating liver injury in T1DM mice than insulin monotherapy, similar to the combined drug therapy. Furthermore, the expression of Wnt/ β -catenin signaling pathway-associated molecules was upregulated in the liver of mice treated with liraglutide or insulin. The results of the present study suggested that liraglutide improves T1DM-induced liver injury and may have important implications for the treatment of nonalcoholic fatty liver disease (NAFLD) in patients with T1DM., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Jie Yu et al.)

Polyphenols are secondary metabolites of plants and used as effective antioxidants in dietary supplements, whose main sources are fruits, vegetables, and grains. To clarify the content and distribution of polyphenols in different fruit species samples accurately, a rapid and sensitive ultrahigh-pressure liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method combining dispersive liquid-liquid microextraction (DLLME) was developed for quantitative determination of fifteen polyphenol compounds in fruit juice. In this method, the targets were first extracted from 1 g of fruit juice sample using 10 mL of 80% ethanol solution by ultrasonic-assisted extraction (UAE). Then, 1.0 mL of UAE extracted solution, 60  μ L of n -octanol and 2.0 mL of H 2 O were performed in the following DLLME procedure. A C 18 reversed-phase column, ZORBAX SB (100 × 4.6 mm, 3.5  μ m), was proposed under gradient elution with 0.1% formic acid aqueous solution and methanol mobile phases for the determination of 15 polyphenols, allowing us to obtain polyphenolic profiles in less than 23.0 min. Under the optimum conditions, the enrichment factors ranged from 162 to 194. The results showed that the 15 polyphenols had linear correlation coefficients ( R 2 ) more than 0.99. The limits of detection (LODs) were between 18.3 and 103.5 ng/g, and the average recoveries were between 96.9 and 116.3% with interday relative standard deviations (RSDs) ranging from 4.4 to 8.2% in all cases. The method was successfully applied to the analysis of real fruit juice samples and presented itself as a simple, rapid, practical, and environment-friendly technique., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Yuxiu Li et al.)

The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects (62.06 ± 16.89 U/mL vs. 56.25 ± 22.61 U/mL, P = 0.001) and exhibited a descending trend across sequential increase of MS component number ( P  for trend = 0.031). SOD activity is modestly correlated with glucose indicators and insulin sensitivity and β -cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity and β -cell function indices. However, the statistical significance of the association between SOD activity and MS was attenuated after adjusting for the Matsuda insulin sensitivity index (ISIM) and insulin secretion-sensitivity index-2 (ISSI-2), suggesting a possible mediating effect. Therefore, we conducted a mediation model analysis, which showed that decreased ISIM and ISSI-2 partially and synergistically mediated the contribution of decreased SOD activity to MS. In conclusion, decreased SOD activity is an independent predictor for increased risk of MS, and insulin resistance and β -cell dysfunction partially mediate the relationship between decreased SOD activity and MS., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Yiwen Liu et al.)

Objectives: In this study, we assessed the effects of dietary magnesium on leukocyte telomere length (LTL)., Designs: The current cross-sectional analysis was based on data collected within a type 2 diabetes project. Settings . Dietary magnesium intake is associated with peripheral blood leukocyte telomere length (LTL). However, few epidemiological studies have evaluated the effects of magnesium on LTL in the clinical setting. Participants . This cross-sectional analysis included 467 participants (34.8% men). Measurements . Serum blood lipid profile, HbA1c, oxidative stress, and proinflammatory mediator levels were measured. Detailed dietary data were obtained using a 24 h food recall. LTL was assessed using a real-time PCR assay. Regression models and simple regulatory models were used for data analysis., Results: There was an inverse relationship between dietary magnesium and LTL ( P < 0.001), with a between-extreme-quarter difference of -0.55. Conversely, there was a positive relationship between dietary magnesium and serum tumor necrosis factor (TNF) α , with an interquarter difference of 3.79 pmol/mL ( P  for trend = 0.006). Multivariate regression analysis revealed that the odds ratios (ORs) for shorter LTL and higher serum TNF α increased with magnesium intake, and the ORs of the differences between extreme quartiles were 2.60 (95% confidence interval (CI): 1.31-5.36; P = 0.003) and 1.98 (95% CI: 1.09-3.59; P = 0.008). There was a direct negative effect of dietary magnesium intake on LTL ( B = -0.002; P = 0.001), which appeared to be indirectly influenced by TNF α (-0.002 to -0.0005)., Conclusions: Dietary magnesium intake may be a critical component of the cellular aging process, and its effect could be partly mediated by TNF α ., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Jie Yu et al.)

It remains unknown how different glucose tolerance status affects the relationships between dietary intake of different tocopherol isoforms ( α -, β -, γ -, and δ -tocopherol) and cellular aging, oxidative stress, and inflammatory markers. The authors conducted a cross-sectional study among 582 Chinese adults with different glucose tolerance status to explore the association between dietary intake of different tocopherol isoforms and cellular aging, oxidative stress, and inflammatory markers. The inverse correlations between non- α -tocopherols and tumor necrosis factor-alpha (TNF- α ) varied substantially across different glucose tolerance status, with the strongest observed in prediabetes ( r = -0.33 for β -/ γ -tocopherol, r = -0.37 for δ -tocopherol, p < 0.01), followed by normal glucose tolerance (NGT). While such correlations were abolished in established diabetes. Furthermore, within prediabetes, the strongest inverse correlations between non- α -tocopherols and TNF- α were observed in impaired fasting glucose (IFG) ( r = -0.42 for β -/ γ -tocopherol, r = -0.55 for δ -tocopherol, p < 0.01), while such correlations were significantly attenuated in individuals with impaired glucose tolerance (IGT) and IFG+IGT. And mediation model analysis displayed that TNF- α mediated the protective effect of non- α -tocopherols on leukocyte telomere length and mitochondrial DNA copy number, which was uniquely observed in prediabetes, while such mediation effect was statistically nonsignificant in NGT and established diabetes. In conclusion, our findings indicate that dietary intake of non- α -tocopherols might protect against cellular aging markers mediated by TNF- α in prediabetes. Individuals with prediabetes, especially for IFG, might benefit from increasing dietary intake of non- α -tocopherol in alleviating inflammation and cellular aging, which might provide a new dietary avenue for delaying diabetes onset., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Yiwen Liu et al.)

Cellular aging markers, including telomere length and mitochondrial function, as well as oxidative stress and inflammation markers influence each other and form a complex network, which is affected in diabetes. However, it remains unknown whether these markers could independently predict future diabetes after adjustment for their mutual effects. We conducted a 3-year longitudinal study in a Chinese cohort that comprised 108 nondiabetic individuals at baseline. The 2-hour 75 g oral glucose tolerance tests were performed at baseline and at 3-year follow-up. At baseline, leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) in leukocytes were determined using the polymerase chain reaction method. Tumor necrosis factor (TNF- α ), interleukin-6, 8-hydroxy-2-deoxyguanosine levels, and superoxide dismutase (SOD) activity were measured by the enzyme-linked immunosorbent assay. Participants who developed diabetes at the 3-year follow-up ( n = 28) had shorter LTL and higher levels of TNF- α and SOD activity at baseline. Baseline LTL was found to be independently associated with the development of diabetes at the 3-year follow-up after the adjustment for mtDNAcn, markers of oxidative stress and inflammation, and conventional diabetes risk factors. Our findings suggest that LTL is an independent predictor for 3-year diabetes risk, which might inform timely prevention and treatment of diabetes. Telomere shortening might be involved in the pathogenesis of diabetes independently of conventional diabetes risk factors, mtDNAcn, or oxidative stress and inflammation pathways., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Yiwen Liu et al.)

Background: Given that the dysregulation of iron homeostasis leads to genomic instability, iron has been linked to cellular aging. However, epidemiological research on dietary iron intake and cellular aging markers is scarce. The aim of this study was to explore the relationship between dietary iron intake and cellular aging markers and to investigate whether tumor necrosis factor- α (TNF α ) mediated this relationship., Methods: We conducted a cross-sectional analysis with a total of 467 subjects. Detailed dietary data were obtained using 24 h food recalls. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) were assessed using real-time PCR assay. The association between dietary iron intake and cellular aging markers and TNF α and superoxide dismutase (SOD) was analyzed by Pearson correlation analysis and regression models adjusted by covariates. Simple mediation models were generated to examine whether TNF α mediated the association between iron intake and cellular aging markers using PROCESS macro Version 3.3., Results: The study population contained more women than men, but their basic demographic and metabolic characteristics did not differ. After adjusting for age, LTL was the same for men and women, while mtDNAcn was lower in men. Multiple linear regression adjusted for confounding factors found that iron intake was negatively associated with LTL only in women and negatively associated with mtDNAcn only in men. Moreover, iron intake was positively associated with TNF α in both women and men but positively associated with SOD only in men. Path modeling showed that TNF α significantly mediated the indirect detrimental effect of iron intake on LTL only in women; in men, mediation of the indirect effect of iron intake on mtDNAcn by TNF α did not reach significance., Conclusions: The study found sex-specific negative associations between dietary iron intake and cellular aging markers in that iron intake had deleterious effects on LTL attrition in women and mtDNAcn in men; only the former was partly mediated by TNF α . Consequently, when dietary iron intake and iron supplementation is recommended, the effects of iron imbalance on genomic stability and cellular aging markers must be considered., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2019 Jie Yu et al.)

Background: Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS) is a severe adverse reaction caused by specific drugs. However, little information is available about sequelae following DIHS/DRESS resolution from an endocrinologist's perspective. This study aimed to investigate the endocrine sequelae following DIHS/DRESS, from clinical feature to etiology., Methods: We retrospectively analyzed the patients diagnosed with DIHS/DRESS in Peking Union Medical College Hospital (PUMCH) during the period of 1 January 2012 to 31 December 2017, and those who developed endocrine disorders after DIHS/DRESS were further examined. We also reviewed the literature, from 1 January 2000 to 31 December 2017, on involvement of endocrine glands in DIHS/DRESS patients., Results: Three patients developed both autoimmune thyroid disease (AITD) and type 1 diabetes (T1DM)/fulminant type 1 diabetes (FT1DM) of the 45 patients. Seven cases involving more than two endocrine glands were reported in the literature. Our results indicated that DIHS/DRESS is a potential etiological factor of autoimmune polyendocrine syndrome (APS), especially APS III., Conclusions: Patients require careful long-term follow-up after DIHS/DRESS. Involvement of endocrine glands, especially FT1DM, should always be monitored in patients with a history of DIHS/DRESS. This study indicated that DIHS/DRESS could lead to APS, especially APS III, providing novel insights into the etiological factors of APS., Competing Interests: All authors declare that they have no any conflicts of interest., (Copyright © 2019 Mingqun Deng et al.)

Objective: Previous studies have revealed dysregulated circulating microRNAs (miRNAs) in patients with type 1 diabetes (T1D). Here, we explored the serum levels of miR-21 , miR-25 , miR-146a , and miR-181a in patients with autoimmune diabetes (T1D and latent autoimmune diabetes of adults (LADA)) compared with type 2 diabetes (T2D) and nondiabetic individuals., Design Patients and Measurements: The serum levels of miR-21 , miR-25 , miR-146a , and miR-181a in patients with T1D ( n  = 29), LADA ( n  = 16), and T2D ( n  = 31) and in nondiabetic individuals ( n  = 19) were determined by quantitative real-time polymerase chain reaction, and receiver-operating characteristic (ROC) curves were evaluated to determine the discriminatory performances of these four miRNAs. Furthermore, target genes and pathways potentially modulated by these four miRNAs were predicted by bioinformatics analysis to investigate the possible functions of these miRNAs in autoimmune diabetes. Subsequently, multiple logistic regression analysis was performed to identify independent predictors for autoimmune diabetes, and a nomogram was established., Results: miR-21 , miR-25 , miR-146a , and miR-181a were significantly downregulated in the serum of patients with autoimmune diabetes compared with those in T2D patients and nondiabetic individuals ( p < 0.001). The areas under the ROC curves of these four miRNAs were greater than 0.80 ( p < 0.001). Bioinformatics analysis suggested that miR-21 , miR-25 , miR-146a , and miR-181a regulated multiple genes in pathways associated with immunity, inflammatory responses, hyperglycemia, and metabolism, which are involved in the pathogenesis of autoimmune diabetes. Multiple logistic regression analysis identified miR-25 (odds ratio (OR): 0.001, p < 0.05), miR-146a (OR: 0.136, p < 0.05), and fasting C-peptide levels (OR: 0.064, p < 0.05) as independent predictors of autoimmune diabetes., Conclusions: miR-25 and miR-146a may serve as potential circulating biomarkers and provide insights into the pathogenesis of autoimmune diabetes., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Yiwen Liu et al.)

Objective: To investigate the association of polymorphisms in uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptor (PPAR γ ) with glucolipid metabolism in Chinese Han population., Methods: Five hundred eighty-nine subjects were divided into normal glucose tolerance (NGT) group ( n = 198) and abnormal glucose tolerance group ( n = 358). HbA1c, blood lipid profile, plasma glucose, and insulin were determined. Insulin sensitivity (HOMA-IR and Matsuda index (ISI M )) and insulin secretion indexes (HOMA- β , early and total phase disposition index) were evaluated. Eight potential functional SNPs in UCP2 and 7 in PPAR γ were selected. SNPs were genotyped on Sequenom MassARRAY platform., Results: The GG genotype of rs2920502 in PPAR γ was associated with decreased risk of impaired glucose tolerance (G allele: OR: 0.818, 95%CI: 0.526-0.969, P = 0.042; GG: OR: 0.715, 95%CI: 0.527-0.97, P = 0.031). The TT genotype of rs3856806 in PPAR γ was associated with increased risk of impaired glucose tolerance (T allele: OR: 1.46, 95%CI: 1.055-2.017, P = 0.022; TT: OR: 1.58, 95%CI: 1.104-2.761, P = 0.032). The GG genotype of rs2920502 in PPAR γ had better blood glucose and increased insulin secretion and had lower HOMA-IR than GC/CC genotypes., Conclusion: It probably could prevent insulin resistance in early stage by classifying the genotype of rs649446 and rs7109266 in UCP2. The GG genotype of rs2920502 in PPAR γ had a decreased risk for diabetes. The TT genotype of rs3856806 in PPAR γ had an increased risk for diabetes.