Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association最新文献

Background: The severe acute respiratory syndrome coronavirus 2 can affect the hypothalamic-pituitary-gonadal axis (HPG) due to the expression of the angiotensin-converting enzyme 2 receptor.

Objectives: To assess the prevalence of hypogonadism and Sertoli cell dysfunction in coronavirus disease 2019 (COVID-19) male survivors.

Method: Male subjects recovered from acute COVID-19 infection were prospectively observed. The primary outcomes included the proportion of hypogonadism, defined biochemically as serum testosterone<230 ng/dL or CFT of<6.4 ng/mL if the total testosterone is between 230-320 ng/m. Sertoli cell dysfunction was defined as inhibin-B level<54.5 pg/mL. Subjects with hypogonadism were followed up at 12 months to assess the recovery of the HPG axis.

Results: Eighty-three subjects aged≥18 years were evaluated at a median of 120 (±35) days post-recovery. Their mean age was 49.50±12.73 years, and the mean BMI was 26.84±5.62 kg/m². Low testosterone was detected in 21 (24.71%) and low inhibin-B was detected in 14 (19.71%) out of 71 subjects at 3 months. Subjects with low testosterone were younger, with a mean age of 43.29±12.03 years (P-0.08) and higher BMI (P-0.012). The severity of COVID-19 infection, duration of hospitalization, and other factors were not significantly associated with low testosterone. At 12 months, 18 out of 21 subjects came for follow-up, of which 9 (50%) showed persistently low testosterone, suggestive of hypogonadism.

Conclusion: Following COVID-19 infection, testosterone levels recovered over time; however, a significant proportion of subjects had low levels at 12-month follow-up. These findings have long-term implications for the management of COVID-19 subjects.

Objective: Antithyroid drug (ATD)-induced agranulocytosis (TIA) is the most serious adverse effect during ATD treatment of Graves' disease (GD). Previously, the MICA gene was reported to be associated with TIA. MICA protein is an important ligand for the NKG2D protein, which is encoded by the KLRK1 gene and KLRC4-KLRK1 read-through transcription. This study further investigated the association between KLRC4-KLRK1 gene polymorphisms and susceptibility to TIA.

Methods: Twenty-eight candidate single nucleotide polymorphisms (SNPs) on KLRC4-KLRK1 read-through transcription were evaluated by the iPLEX MassARRAY system in 209 GD control patients and 38 TIA cases.

Results: A significant association of rs2734565 polymorphism with TIA was found (p=0.02, OR=1.80, 95% CI=1.09-2.96). The haplotype C-A-A-C-G, including rs2734565-C, was associated with a significantly higher risk of TIA (p=4.79E-09, OR=8.361, 95% CI=3.737-18.707). In addition, the interval time from hyperthyroidism to agranulocytosis onset was shorter in patients carrying the rs2734565-C allele than in non-carrying groups (45.00 (14.00-6570.00) d vs. 1080.00 (30.00-3600.00) d, p=0.046), and the interval from ATD treatment to agranulocytosis onset was also shorter in patients carrying rs2734565-C allele (29.00 (13.00-75.00) d vs. 57.50 (21.00-240.00) d, p=0.023).

Conclusions: The findings suggest that the KLRC4-KLRK1 gene polymorphism is associated with susceptibility and progression of ATD-induced agranulocytosis. Patients carrying the rs2734565-C allele had a higher susceptibility and faster onset time of TIA.

Objective: Type 2 diabetes mellitus (T2DM) is a common metabolic disorder with rising incidence worldwide. This study explored the anti-T2DM role of vitamin D, thereby providing novel therapeutic strategies.

Methods: C57BL/6 J mice and MIN6 cells were used to induce in vivo T2DM and damaged β-cell models, respectively. Body weights, fasting blood glucose, and fasting insulin were measured in mice. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted on mice. Lipid indices (TG, TC, LDL-C, and HDL-C) were detected in mouse serum. Hematoxylin-eosin staining was used to evaluate pancreatic tissue injury. ELISA was used to assess insulin and oxidative stress (OS) markers (MDA, GSH, and SOD) in mice and MIN6 cells. Production of ROS was detected in islet β-cells and MIN6 cells. Cell viability and apoptosis were evaluated using CCK-8 and flow cytometry, respectively. QRT-PCR and western blotting were used to detect pro-inflammatory factors (TNF-α and IL-6) and endoplasmic reticulum stress (ERS) markers (CHOP and GRP78), respectively.

Results: Vitamin D reduced body weights, fasting blood glucose, and insulin and ameliorated glucose tolerance and insulin sensitivity in T2DM mice. Besides, vitamin D decreased serum TG, TC, LDL-C, and increased HDL-C in T2DM mice. Vitamin D inhibited pancreatic histopathological injury, cell apoptosis, OS, and β-cell decline in T2DM mice. Moreover, vitamin D alleviated cell death, insufficient insulin secretion, inflammation, OS, and ERS in damaged MIN6 cells. Notably, N-acetyl-L-cysteine (an OS inhibitor) enhanced these effects of vitamin D.

Conclusions: Vitamin D relieved T2DM symptoms by alleviating OS-induced β-cell impairment.

Painful diabetic neuropathy (PDN) is a serious and very common complication of diabetes mellitus (DM). It negatively affects the quality of life, increases morbidity and poses a financial burden on the health care system. Currently, treatment of PDN focuses on glycaemic control, while pathogenesis-oriented therapy has not yielded satisfactory results. The need to improve therapy remains. There is accumulating evidence on the potential benefit of nutritional interventions. This narrative review aims to examine the potential benefit of dietary and nutritional supplementation for PDN management. According to the preliminary research, supplementation with vitamin E, B-complex, omega-3 fatty acids, CoQ10 or N-acetylcysteine seems to be associated with promising results in improving PDN symptoms.

Background: Clinical observation suggests the atheroprotective effect of chloroquine and its derivatives, while its mechanism remains unclear. This study aimed to observe the protective effect of chloroquine against atherosclerosis and explore the underlying mechanism.

Methods: Ataxia telangiectasia mutated (ATM) wild-type or haploinsufficient apolipoprotein-E-knockout (ATM^+/+ApoE^-/- or ATM^+/-ApoE^-/-) mice were treated with different dosages of chloroquine. Anti-CD25 antibody was used to deplete natural Tregs in ATM^+/+ApoE^-/- mice. The atherosclerotic burden in different groups of mice was comprehensively evaluated by H&E staining and Masson staining. The effect of chloroquine on the regulatory T cells (Tregs) was assessed in vivo and in vitro by flow cytometry and immunohistochemical staining. The expression of related proteins was detected by real-time polymerase chain reaction and western blotting.

Results: In ATM^+/+ApoE^-/- mice, chloroquine alleviated atherosclerotic lesions, stabilized the plaque, and increased Treg counts in the atherosclerotic lesions and spleens. However, in ATM haploinsufficient mice (ATM^+/-ApoE^-/-), chloroquine no longer prevented atherosclerosis or impacted Treg counts. Abolishing Treg cells using an anti-CD25 antibody in vivo abrogated the atheroprotective effect of chloroquine. In vitro, chloroquine promoted the differentiation of Tregs from naïve T cells, which was accompanied by enhanced ATM/AMP-activated protein kinase (AMPK) activity and reduced downstream mammalian target of rapamycin (mTOR) activity.

Discussion: These findings suggest that chloroquine ameliorates atherosclerosis and stabilizes plaque by modulating Tregs differentiation through the regulation of the ATM/AMPK/mTOR pathway.

Small molecules such as ROCK inhibitors (Fasudil) and inducer of definitive endoderm 1 (IDE1) can promote differentiation of definitive endoderm, but their effects remain controversial. Therefore, we attempted to verify the effect of these small molecules on promoting definitive endoderm differentiation and found that Fasudil or IDE1 alone could not achieve a similar effect as activin A. On the contrary, CHIR99021 could efficiently promote definitive endoderm differentiation. Nearly 43.4% of experimental cells were SRY-box transcription factor 17 (SOX17)-positive under the synergistic effect of IDE1 and CHIR99021, but its ability to differentiate towards definitive endoderm was still insufficient. Transcriptional analysis and comparison of IDE1 and CHIR99021 synergistic groups (IC) and activin A and CHIR99021 synergistic groups (AC) showed significantly down-regulated definitive endoderm markers in the IC group compared with those in the AC group and the differences between the two groups were mainly due to bone morphogenetic proteins (BMP4) and fibroblast growth factor 17 (FGF17). Further single-cell transcriptome analysis revealed lower expression of BMP4 in SOX17-positive populations, while mothers against decapentaplegic homolog (SMAD) protein translation signal and FGF17 in the AC group were higher than that in the IC group. Western blot analysis showed a significant difference in levels of p-SMAD2/3 between AC and IC groups, which suggests that regulating p-SMAD2/3 may provide a reference to improve the differentiation of definitive endoderm.

Background: Little is known about the relationship between signal intensity patterns on T2-weighted magnetic resonance imaging (MRI) in non-functioning pituitary adenomas (NFPAs).

Objective: In this study, the clinical, hormonal, histological features, and therapeutic responses were evaluated according to the T2 signal intensity in NFPAs.

Methods: This retrospective and multicenter study included a group of 166 NFPA patients (93 men, 56%, mean age 58.5 ±14.8 yr).

Results: Approximately half of the tumors (n=84, 50.6%) were hyperintense, while 34.3% (n=57) and 15.1% (n=25) were iso- and hypointense, respectively. The median maximum tumor diameter of the isointense group [16 (13-25) mm] was significantly lower than that of the hyperintense [23 (16.6-29.7) mm] group (p=0.003). Similarly, the tumor volume of the isointense group [1,523 (618-5,226) mm³] was significantly lower than that of the hyperintense [4,012 (2,506-8,320) mm³] group (p=0.002). Chiasmatic compression occurred less frequently in tumors with isointense signal characteristics (38.6%) compared to tumors with hypointense (68%) and hyperintense (65.5%) signal characteristics (p=0.003). Invasive adenomas (p=0.001) and the degree of cavernous sinus invasion (p<0.001) were more frequent in the hyperintense adenoma group compared to the remaining groups. Plurihormonal tumors and silent lactotroph adenomas were more frequent in the isointense tumor group.

Conclusion: In conclusion, hyperintensity on T2-weighted MRI in NFPAs is associated with larger and more invasive tumors compared to isointense NFPAs.

Aims: Offspring exposed to an adverse fetal environment, such as gestational diabetes, may manifest increased susceptibility to several chronic diseases later in life. In the present study, the cardiovascular function of three different ages of offspring from diabetic rats was evaluated.

Methods and results: Diabetes mellitus was induced in pregnant rats by a single dose of streptozotocin (50 mg/kg). The offspring from diabetic (OD) and control rats (OC) were evaluated at three different ages: 6, 12 or 18 months. In the corresponding OC groups, fasting glycemia, baseline mean arterial pressure, and sympathetic tonus increased in the OD rats at 12 (OD12) and 18 (OD18) months of age, while cardiac hypertrophy was observed in all OD groups. Cardiac function evaluation in vivo showed low left ventricular systolic pressure and+dP/dt in the OD18 rats, suggesting a systolic dysfunction. OD12 and OD18 groups showed high left ventricle end-diastolic pressure, suggesting a diastolic dysfunction. OD groups showed an age-related impairment of both baroreflex-mediated tachycardia and baroreflex-mediated bradycardia in OD12 and OD18 rats. In isolated hearts from OD18 rats, both inotropic and tachycardiac responses to increasing isoproterenol were significantly reduced compared to the corresponding OC group.

Conclusion: These results suggest that gestational diabetes triggers the onset of hyperglycemia hypertension with impaired baroreflex sensitivity and heart failure in older age of offspring, representing important risk factors for death. Therefore, ensuring optimal glycemic control in diabetic pregnancy is important and serves as a key to preventing cardiovascular disease in the offspring in their older age.

Objective: To assess the prognostic value of clinicopathological factors as well as BRAF and TERT promoter mutations in predicting distant metastasis in patients with papillary thyroid cancer.

Design: The status of BRAF and TERTp mutations were available in 1,208 thyroid cancer patients who received thyroidectomy at Jiangyuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine from January 2008 to December 2021. Based on inclusion criteria, 99 distant metastasis thyroid cancers (DM-TCs) and 1055 patients without DM (Non-DM-TCs) were retrospectively reviewed.

Results: After univariate and multivariate analyses, a risk model was established for DM prediction based on factors: T3/T4 stage, lymph node metastasis (LNM) number over 5, and BRAF/TERT mutations (TLBT). It was defined based on the number of TLBT factors: low risk (no risk factor, n=896), intermediate risk (1 risk factor, n=199), and high risk (≥2 risk factors, n=59). Notably, compared with patients with low and intermediate risks, patients assigned to high TLBT risk have a shorter time of DM disease-free survival. Except for gene mutation, other factors were also included in the 2015 American Thyroid Association (ATA) risk guideline. Comparing with the ATA risk category, this risk model showed a better performance in predicting DM-TCs.

Conclusions: This study proposes a TLBT risk classifier consisting of T3/T4 stages, LNM (n>5), and BRAF+TERTp mutations for predicting DM-TCs. TLBT risk stratification may help clinicians make personalized treatment management and follow-up strategies.