Hasil untuk "Diseases of the endocrine glands. Clinical endocrinology"

Gui-Jun Lu, Ying Zhao, Rui Huang

BackgroundThis study aimed to establish a diagnostic nomogram to predict the early death risk in older patients with primary intracranial glioma and to identify the high-risk population in those patients to provide them with specialized care to increase their benefit from survival.MethodsPatients aged 60 years and older with histologically confirmed intracranial glioma were identified in the Surveillance, Epidemiology and End Results (SEER) database. Initially, they were divided into a training set and a validation set in a 7:3 ratio. Next, univariate and multivariate logistic regression were employed to identify independent risk variables, which were used to develop a diagnostic nomogram further. Additional analyses were performed on the diagnostic nomogram’s performance, including calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). A mortality risk classification system was ultimately developed using the diagnostic nomogram.ResultsThis study included 8,859 individuals diagnosed with primary intracranial glioma. The participants were randomly split into two groups: a training set consisting of 6203 individuals and a validation set consisting of 2,656 individuals, with a ratio of 7 to 3. Univariate and multivariate logistic regression analyses on early death showed 7 independent risk variables (age, median household income, histological type, tumor grade, surgery, radiation therapy, and systemic therapy sequence with surgery) in the training set. A diagnostic nomogram for predicting the early death risk was created based on these variables. Calibration curves showed a high agreement between the expected and actual probabilities. The area under the curves (AUC) for the training and validation sets were 0.798 and 0.811, respectively. Meanwhile, the novel-created diagnostic nomogram had the highest AUC value compared to each independent risk variables, which showed that the nomogram had the best discriminatory ability. The DCA indicated that the nomogram has the potential to provide greater clinical advantages across a broad spectrum of threshold probabilities. Furthermore, a nomogram-based risk classification system was constructed to help us identify the high-risk population facing early death.ConclusionsThis study created a novel diagnostic nomogram to predict the probability of early death in older patients with intracranial glioma. In the meantime, a nomogram-based risk classification system was also constructed to help us identify the high-risk population facing early death in older patients with intracranial glioma and provide them with specialized care to increase their benefit from survival.

Dang Wenjiao, Wang Yurou, Xie Jiaqi et al.

BackgroundGut microbiota has demonstrated an increasingly important role in the onset and development of type 2 diabetes mellitus (T2DM), Further investigations have revealed the interactions between drugs and the gut microbiome. However, there are still gaps in research regarding the potential interactions between the gut microbiota and GLP-1 and their therapeutic response in people with T2DM. In addition, Fecal microbiota transplantation (FMT) has become a promising strategy for patients with T2DM.Design, animals and measurements50 healthy male C57BL/6 mice were fed a high-fat diet in combination with STZ to establish a T2DM mouse model. 40 mice were divided into the T2DM group (n=10) and the PEX168 group (n=30). the PEX168 group was divided into two subgroups of the IE group (HbA1c ≤6. 5%, n=12) and the SE group (HbA1c >6. 5%, n=12), 12 mice in each group. Using IE mice as fecal donors and SE mice as recipients, fecal microbiota transplantation was performed between the two groups, the FMT group (given fecal bacterial suspension, n=5) and the Sham group (given equal amounts of sterile saline, n=5). The intestinal microorganisms of mice in the IE group (donor) and SE group (recipient) were also analyzed for differences. To assess the protective effect of FMT on drug efficacy and T2DM, and to explore the underlying mechanisms.ResultsAfter 10 weeks, compared with the control group, the HbA1c of the experimental group was significantly reduced, still, the level of HBA1c of the mice in the unsatisfactory group was significantly higher than that in the ideal group. Compared with the unsatisfactory group, fasting blood glucose, 2h postprandial blood glucose, blood glucose AUC and body weight were significantly reduced in the ideal group. 16srDNA sequencing showed that the levels of Bacteroidota, Akkermansia, Parabacteroides, Bifidobacteria and other bacteria in the ideal efficacy group were significantly higher than those in the non-ideal efficacy group (P<0.05). The levels of Firmicutes, Romboutsia, Clostridium, Turicibacter and other bacteria in the unsatisfactory group were significantly higher than those in the ideal group (P<0.05). The dominant flora of mice in the ideal drug efficacy group was negatively correlated with HbA1c and blood sugar, and the dominant flora of mice in the unsatisfactory drug efficacy group was positively correlated with pro-inflammatory factors such as blood sugar. Moreover, FMT treatment significantly improved the efficacy of PEX168 and liver steatosis in the group with unsatisfactory efficacy.ConclusionIn summary, we used the combined method of 16S rDNA and metabolomics to systematically elucidate the efficacy of microflora on PEX168 and the possible mechanism of FMT in treating T2DM by PEX168. The difference in intestinal flora between individuals can affect the therapeutic effect of drugs. Moreover, FMT therapy can affect multiple metabolic pathways and colonization of beneficial bacteria to maintain the drug’s therapeutic effect on T2DM mice.

Hye In Kim, Jun Young Kim, Jung Hwan Cho et al.

Background The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design. Methods This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models. Results During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR, 1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD. Conclusion In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Jing Peng, Huazhang Miao, Li Zhang et al.

ObjectiveTo examine the associations between well-controlled gestational diabetes mellitus (GDM) and early neurodevelopmental trajectories in offspring.MethodsThis retrospective cohort study included 2810 mother–infant pairs from Guangdong Women and Children Hospital (2016–2022). GDM was diagnosed via a 75 g oral glucose tolerance test at 24–28 gestational weeks, and women with well-controlled GDM were those who maintained blood glucose levels defined as a third-trimester HbA1c < 6% without requiring medication. Neurodevelopment was assessed via the Children’s Neuropsychological and Behavioral Scale-Revision 2016 at 6 and 12 months of age.ResultsAmong 2810 mother–infant pairs, 451 (16.05%) were diagnosed with GDM. Compared with non-GDM mothers, mothers with GDM had a greater median age (31.00 vs. 29.00 years; P < 0.001) and prepregnancy BMI (21.26 vs. 20.20 kg/m²; P < 0.001). No significant differences were observed in neonatal sex, birth weight or low birth weight (<2500 g) proportions. Neurodevelopmental assessments at 6 and 12 months revealed no significant differences in gross motor, fine motor, or adaptive behavior; language; or personal–social scores (all P > 0.05). Adjusted multivariate analyses revealed no associations between GDM and neurodevelopmental delay (≥2 subdomains below the threshold) at 6 months (OR = 0.92, 95% CI: 0.57–1.48; P = 0.739) or 12 months (OR = 0.87, 95% CI: 0.58–1.29; P = 0.479).ConclusionsWell-controlled GDM was not associated with adverse neurodevelopmental outcomes in early infancy, suggesting that optimized perinatal management may mitigate risks.

Yong Jun Choi, Aram Yang

BackgroundPrader–Willi syndrome (PWS) is a rare genetic disorder characterized by severe multisystem comorbidities and increased mortality. Although growth hormone therapy (GHT) is widely used as standard care, population-based evidence on its long-term safety, particularly in relation to mortality and type 2 diabetes mellitus (T2DM), remains limited. We aimed to investigate the associations between GHT duration, mortality, and T2DM incidence in PWS.MethodsThis is a nationwide cohort study using the Korean National Health Insurance Service database. A total of 385 individuals with PWS were identified between January 2005 and February 2023. GHT duration was the primary exposure. All-cause mortality was analyzed using Cox proportional hazards models, and T2DM risk was evaluated using multivariable logistic regression adjusted for age, comorbidities, and GHT duration.ResultsGHT duration did not directly impact mortality (OR 1.00, 95% CI: 0.99–1.00); however, peripheral vascular disease (aOR 10.66, 95% CI: 1.07–106.56), renal disease (aOR 17.45, 95% CI: 1.17–259.93), adrenal insufficiency (aOR 23.90, 95% CI: 3.19–178.34), and behavioral disorders (aOR 29.51, 95% CI: 2.64–329.95) were significant predictors of all-cause mortality. Longer GHT duration was independently associated with higher T2DM risk (aOR 1.06, 95% CI: 1.02–1.11). Older age, age at PWS diagnosis, and comorbidities (peptic ulcer disease, mild liver disease, and diabetes insipidus) were additional risk factors.ConclusionsGHT was not a direct predictor of mortality in PWS, which was instead influenced by comorbidities. However, its prolonged use was linked to increased T2DM. These findings support individualized risk assessment and metabolic monitoring in patients with PWS receiving GHT.

Paweł Pietruski, Katarzyna Kosińska-Kaczyńska, Agnieszka Osińska et al.

IntroductionTwin gestation is related to a higher risk of hypertensive disorders in pregnancy with possible risk stratification depending on chorionicity. It may be related to differences in plasma renin-angiotensin-aldosterone components between monochorionic and dichorionic twin pregnancies. The study aimed to analyze the plasma ANG II and ANG 1-7 concentrations in women with monochorionic and dichorionic twin gestation.MethodsA prospective observational study included 79 women between 32 and 34 weeks of gestation with twin pregnancy (31 with monochorionic gestation and 48 with dichorionic gestation). Angiotensin II and angiotensin 1-7 concentrations were measured in the collected blood samples.ResultsNo significant differences were observed in angiotensin II concentrations between the dichorionic and monochorionic group with significantly higher levels of angiotensin 1-7 being observed in the dichorionic group. Angiotensin 1-7 level was higher than angiotensin II in 20 women (64.5%) in the monochorionic group and in 42 women (87.5%, p=0.01) in the dichorionic group. Higher plasma concentrations of angiotensin II and lower concentrations of angiotensin 1-7 were found in 5 women with gestational hypertension and in 3 with preeclampsia compared to normotensive women.DiscussionIt is the first study investigating angiotensin II and angiotensin 1-7 in twin pregnancies regarding chorionicity. Our results showed that plasma angiotensin 1-7 concentration was related to chorionicity, while plasma angiotensin II level was not. In most women with twin gestation angiotensin 1-7 concentration exceeded the concentration of angiotensin II. A switch in the relation between angiotensin II and angiotensin 1-7 was observed in hypertensive pregnant women.

Zachary Brown, Takeshi Yoneshiro

Brown and beige adipocytes utilize a variety of substrates for cold-induced thermogenesis, contributing to the clearance of metabolites in circulation and, consequently, metabolic health. Food-derived compounds that exhibit agonistic activity at temperature-sensitive transient receptor potential channels may serve as cold mimics to elicit thermogenesis and substrate utilization in brown adipose tissue (BAT). In addition to fatty acids and glucose, branched-chain amino acids (BCAAs), which are essential amino acids obtained from foods, are actively catabolized in BAT through mitochondrial BCAA carrier (MBC). The relative contribution of BCAAs to fueling the tricarboxylic acid cycle as a substrate (i.e., anaplerosis) is estimated to be relatively small, yet BCAA catabolism in BAT exerts a critical role in systemic insulin sensitivity. The nature of this apparent tension remained unclear until the recent discovery that active BCAA catabolism in BAT through MBC is critical for the synthesis of metabolites such as glutathione, which is delivered to the liver to improve hepatic insulin sensitivity through redox homeostasis. Novel mechanistic insights into the control of BAT function and systemic metabolism reveal the therapeutic potential of food-derived compounds for improving metabolic flexibility and insulin sensitivity.

Ceren Erdoğan Eroğlu, Süheyla Görar, Barış Paksoy

Infertility is a significant health problem that affects many couples in the reproductive age range globally. While only the male factor is responsible for 20%-30% of cases of infertility, contributing to a further 20%. We aimed to describe a rare cause of male infertility, a male patient with 45,X/46,XY mosaic chromosome structure. The patient presented to our endocrinology department due to infertility. Phenotypically, the patient appeared as a normal male with normal development of the penis and secondary sex characteristics. Both testicles were small in the scrotum. Azoospermia was detected in the spectrogram. The patient underwent testicular sperm extraction using microdissection, but spermatozoa were not found in either of the testicles. In the cytogenetic and molecular cytogenetic examination of the patient’s peripheral blood, the chromosome structure was reported as a 45,X[22]/46,XY[8] mosaic karyotype, and Y microdeletion. 45,X/46,XY, sometimes called mixed gonadal dysgenesis, affects hormonal balance, gonadal development, growth, and fertility, and presents a wide range of clinical manifestations. Similar to our case, these patients may have an entirely male phenotype. Even when the patient exhibits phenotypical normal male characteristics, karyotype anomalies should always be considered when evaluating the infertility associated with azoospermia.

Giovanna Muscogiuri, Luigi Barrea, Evelyn Frias-Toral et al.

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Sefa Tan, Zafer Gunendi, Jale Meray et al.

Abstract Background The aim of this study is to compare muscle strength and architecture between type 1 diabetes patients and healthy volunteers and to assess whether there is an ultrasonographic structural change in this population. Methods Thirty-two patients with T1D (23 female, 9 male) with an age average of 31.3 ± 8.7 years, matched in terms of age, gender, height, weight and physical activity were included in the study. In the T1D and control group, ultrasonographic measurements of quadriceps femoris muscle (RF, VI, VM, VL) and pennate angle (VI, VM, VL) were performed. Muscle strength values were measured using isokinetic dynamometer system at angular velocities of 60º/s and 180º/s in both groups. Results Initially, both groups were similar in demographic and clinical characteristics (p > 0.05). In the T1D group, there was a statistically significant difference in flexion/extension peak torque measurements at an angular velocity of 60º/s compared to the control group (p < 0.05). In support of these isokinetic measurements, RF, VI, VM, VL muscle thicknesses and VI, VM pennate angle measurements in T1Ds were significantly lower (p < 0.05). When the T1D group was subgrouped according to HbA1C and diabetes duration, there was no significant difference in ultrasonographic and isokinetic measurements between the two groups (p > 0.05). When the T1D group was subgrouped, in the group that used insulin pump RF, VI, VM muscle thickness measurements were significantly higher (p < 0.05) than the group using subcutaneous insulin. Conclusions This study supports that muscle strength and architecture are adversely affected in the T1D patient group, insulin deficiency is a risk factor for sarcopenia and this can be shown through ultrasonography. It can also be said that insulin pump use has more positive effects in terms of diabetic myopathy than subcutaneous insulin, and diabetic myopathy develops independently of other diabetic complications. As a result, the muscle architecture of T1D people is adversely affected by insulin deprivation, so regular physical activity should be an integral part of diabetes treatment.

Peter Igaz

Semra Şen, Deniz Özalp Kızılay, Fatma Taneli et al.

Objective:Neutrophil gelatinase-associated lipocalin (NGAL) is one of the new biomarkers for detecting acute renal injury. There are studies showing the relationship between NGAL and renal injury in obese children. The aim of this study was to investigate whether urinary levels of NGAL, kidney injury molecule-1, and serum cystatin C are increased in insulin resistance (IR) patients before the development of diabetes.Methods:Cross-sectional, case-controlled study that included non-diabetic obese children and adolescent patients with IR and a nondiabetic obese control group with no IR, who attended a tertiary center pediatric endocrinology outpatient clinic between 2016-2018. Those with diabetes mellitus and/or known renal disease were excluded. NGAL and creatinine (Cr) levels were evaluated in the morning spot urine from all participants. Serum renal function was evaluated.Results:Thirty-six control and 63 IR patients were included in the study, of whom 68 (68.7%) were girls. The mean age of all participants was 13.12±2.64 years and no statistically significant difference was found between the two groups in terms of age or gender distribution. Median (range) spot urinary NGAL (u-NGAL) values in the IR group were significantly higher at 26.35 (7.01-108.7) ng/mL than in the control group at 19.5 (3.45-88.14) ng/mL (p=0.018). NGAL/Cr ratio was also significantly higher in the IR group compared to the control group (p=0.018).Conclusion:Obese pediatric patients with IR were shown to have elevated levels of u-NGAL, a marker of renal injury. u-NGAL examination may show early renal injury before development of diabetes.

Ki-Woon Kang, Minho Ok, Seong-Kyu Lee

Obesity increases the risk of cardiovascular disease through various influencing factors. Leptin, which is predominantly secreted by adipose tissue, regulates satiety homeostasis and energy balance, and influences cardiovascular functions directly and indirectly. Leptin appears to play a role in heart protection in leptin-deficient and leptin-receptor-deficient rodent model experiments. Hyperleptinemia or leptin resistance in human obesity influences the vascular endothelium, cardiovascular structure and functions, inflammation, and sympathetic activity, which may lead to cardiovascular disease. Leptin is involved in many processes, including signal transduction, vascular endothelial function, and cardiac structural remodeling. However, the dual (positive and negative) regulator effect of leptin and its receptor on cardiovascular disease has not been completely understood. The protective role of leptin signaling in cardiovascular disease could be a promising target for cardiovascular disease prevention in obese patients.

Sundong Lin, Lechu Yu, Yongqing Ni et al.

BackgroundEpithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study.MethodsType 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4′-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months.ResultsDN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2).ConclusionFGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.

Samantha Chapman, Dylan Luc Pham, Michael Lee Ko et al.

Introduction Diabetic retinopathy (DR) is the leading cause of blindness among the working population in the USA. Current therapies, including anti-vascular endothelial growth factor treatments, cannot completely reverse the visual defects induced by DR. MicroRNA-150 (miR-150) is a regulator that suppresses inflammation and pathological angiogenesis. In patients with diabetes, miR-150 is downregulated. As chronic inflammation is a major contributor to the pathogenesis of DR, whether diabetes-associated decrease of miR-150 is merely associated with the disease progression or decreased miR-150 causes retinal inflammation and pathological angiogenesis is still unknown.Research design and methods We used high-fat diet (HFD)-induced type 2 diabetes (T2D) in wild type (WT) and miR-150 knockout (miR-150-/-) mice for this study and compared retinal function and microvasculature morphology.Results We found that WT mice fed with an HFD for only 1 month had a significant decrease of miR-150 in the blood and retina, and retinal light sensitivity also decreased. The miR-150-/- mice on the HFD developed diabetes similar to that of the WT. At 7–8 months old, miR-150-/- mice under normal diet had increased degeneration of retinal capillaries compared with WT mice, indicating that miR-150 is important in maintaining the structural integrity of retinal microvasculature. Deletion of miR-150 worsened HFD-induced retinal dysfunction as early as 1 month after the diet regimen, and it exacerbated HFD-induced T2DR by further increasing retinal inflammation and microvascular degeneration.Conclusion These data suggest that decreased miR-150 caused by obesity or diabetic insults is not merely correlated to the disease progression, but it contributes to the retinal dysfunction and inflammation, as well as the development of DR.

Chao Lou, Han-Zhi Wu, Cui-Yun Qin et al.

A 27-year-old patient with azoospermia and low intelligence was reported having a rare karyotype 47,XYY,dup(13q12.11),t(4;9)(q21.1;q22.3),r(21)(p12q22.3). Clinical genetic tests, including next-generation sequencing (NGS), karyotyping, fluorescence in situ hybridization (FISH), and azoospermia factor (AZF) microdeletions, were conducted. The results showed that (1) one copy of chromosome 21 lost a short arm and appeared as a marker, but subsequent detection confirmed that it was a ring 21; (2) there was a reciprocal translocation between chromosome 4 and chromosome 9; (3) NGS revealed a duplication of 0.3 Mb on 13q12.11 and two Y chromosomes; (4) the Y chromosome showed no AZF microdeletions; and (5) FISH confirmed the two Y chromosomes. To our knowledge, this is the first reported case with rare karyotype, combined with four abnormal chromosomal changes simultaneously. Because no Online Mendelian Inheritance in Man genes were found in duplication fragment on 13q12.11, this duplication is not associated with low intelligence.

Girish Parmar, Manoj Chadha

Ye An Kim

Zi-Di Xu, Wei Zhang, Min Liu et al.

This study aims to summarize and analyze the clinical manifestations, genetic characteristics, treatment modalities and long-term prognosis of congenital hyperinsulinemia (CHI) in Chinese children. Sixty children with CHI, who were treated at Beijing Children’s Hospital from January 2014 to August 2017, and their families, were selected as subjects. The CHI-related causative genes in children were sequenced and analyzed using second-generation sequencing technology. Furthermore, the genetic pathogenesis and clinical characteristics of Chinese children with CHI were explored. Among the 60 CHI children, 27 children (27/60, 45%) carried known CHI-related gene mutations: 16 children (26.7%) carried ABCC8 gene mutations, seven children (11.7%) carried GLUD1 gene mutations, one child carried GCK gene mutations, two children carried HNF4α gene mutations and one child carried HADH gene mutations. In these 60 patients, eight patients underwent 18F-L-DOPA PET scan for the pancreas, and five children were found to be focal type. The treatment of diazoxide was ineffective in these five patients, and hypoglycemia could be controlled after receiving partial pancreatectomy. In conclusion, ABCC8 gene mutation is the most common cause of CHI in Chinese children. The early genetic analysis of children’s families has an important guiding significance for treatment planning and prognosis assessment.