BackgroundDiabetic nephropathy (DN) represents one of the most prevalent microvascular complications of type 2 diabetes mellitus (T2DM). The pathogenesis of DN is significantly influenced by the inflammatory response. Thus, the current meta-analysis aimed to assess the diagnostic accuracy of neutrophil-to-lymphocyte ratio (NLR) in early DN and DN.MethodsCochrane, Pubmed, Embase, and Web of Science were retrieved from database establishment to August 31, 2024. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was utilized to assess the quality of included studies. This meta-analysis was carried out via Stata16.0 and Revman 5.3 software.ResultsFinally, this meta-analysis incorporated 18 studies, of which 5 were early DN studies, involving 232 patients with early DN, and 13 were DN studies, involving 4,818 patients with DN. The results indicated that the diagnostic sensitivity of NLR for early DN was 0.83 [95% CI: 0.60-0.94], the specificity was 0.76 [95% CI: 0.61-0.86], and the area under the receiver operating characteristic curve (AUROC) was 0.85 [95% CI: 0.81-0.88]. The diagnostic sensitivity of NLR for DN was 0.73 [95% CI: 0.67-0.79], the specificity was 0.70 [95% CI: 0.59-0.79], and the AUROC was 0.78 [95% CI: 0.74-0.81].ConclusionsNLR exhibited moderate performance in diagnosing both early DN and DN, and its diagnostic accuracy was higher in early DN than in DN. Due to the limitations of existing studies, further studies are required to verify the findings.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024591926.
Diseases of the endocrine glands. Clinical endocrinology
Rebecca John, Kripa E. Cherian, Patricia Sebastian
et al.
Breast cancer, the most common hormone responsive cancer, is on a rise both globally and in India. With increased longevity of breast cancer survivors, addressing long-term complications such as osteoporosis is crucial. Several mechanisms contribute to the bone loss seen in breast cancer patients, including age, post-menopausal status, chemotherapy, and other adjuvant therapies received. Appropriate evaluation and counselling on the risks of therapy with aromatase inhibitors on bone health are much needed. Timely initiation of anti-resorptive medication can help improve bone mass, reduce the incidence of fractures, and improve quality of life.
Diseases of the endocrine glands. Clinical endocrinology, Diseases of the digestive system. Gastroenterology
ObjectiveThis study aims to investigate the relationship between newly identified inflammatory indicators and IR in patients with T2DM, thereby providing a reference basis for the early clinical prevention, diagnosis, and treatment of IR in patients with T2DM.MethodsA total of 779 patients with T2DM admitted to the Endocrinology Department of our hospital from January 2022 to December 2024 were included in the observation group. Five hundred healthy individuals who underwent physical examinations during the same period were randomly selected as the control group. Patients in the observation group were divided into the IS group, the EIR group, and the SIR according to the HOMA-IR level. Analyze the relationship between the four indicators and IR in patients with T2DM, and observe whether they are independent risk factors for IR in T2DM patients, as well as analyze their clinical utility.ResultsCompared with the control group, the levels of inflammatory indicators SII, SIRI, MHR and UHR in the observation group were significantly increased. The levels of SII, SIRI, MHR and UHR in the EIR group and the SIR Group were significantly higher than those in the IS group. Moreover, with the increase in HOMA-IR score, all four inflammatory indicators showed an upward trend. The results of Spearman’s rank correlation analysis showed that all four indicators were positively correlated with IR in patients with T2DM. Multivariate ordered logistic regression analysis showed that all four indicators were independent risk factors for IR in patients with T2DM. The ROC results indicated that SII, SIRI, MHR and UHR could serve as potential discriminatory ability indicators for evaluating the degree of IR in patients with T2DM.ConclusionThe levels of SIRI, SII, UHR and MHR in patients with T2DM increase and are positively correlated with IR. They are independent risk factors for IR in patients with T2DM and have clinical utility to a certain extent. They can provide a reference basis for the early clinical prevention, diagnosis and treatment of IR in patients with T2DM.
Diseases of the endocrine glands. Clinical endocrinology
Jorgen Thorup, Jorgen Thorup, Simone Hildorf
et al.
Cryptorchidism in males constitutes a notable risk factor for both infertility and testicular cancer. Infertility in adulthood is closely linked to the germ cell status in childhood. Furthermore, the significance of germ cell status is important as more than 95% of all reported testicular malignancies are germ cell tumors. The review aims to elucidate the pathogenesis of germ cells in cryptorchid testes concerning their association with infertility and testicular malignancies. Impaired germ cell numbers are evident in cryptorchid testes even during antenatal and neonatal stages. In cryptorchidism there is a rapid decline in germ cell number within the first year of life, partially attributed to physiologic gonocyte apoptosis. Additionally, germ cells fail to differentiate normally during mini-puberty leading to reduced germ cell proliferation and delayed clearance of gonocytes from the seminiferous epithelium. Absence of germ cells in testicular biopsies occurs already 10 months of age and germ cell deterioration progressively worsens with approximately 50% of persisting cryptorchid testes lacking germ cells during puberty. The deficient germ cell maturation and proliferation leads to later infertility. Elevated temperature in the cryptorchid testes and also hormonal deficiency contribute to this phenomenon. Germ cell neoplasia in situ (GCNIS) originating during fetal development may manifest in rare cases associated with disorders of sexual development, chromosomal abnormalities in boys, specific syndromes, and teratomas that include cryptorchidism. In adults, the presence of GCNIS predominantly represents a new histology pattern before invasive germ cell cancer is demonstrated and is neither congenital nor related to abnormal gonocyte transformation.
Diseases of the endocrine glands. Clinical endocrinology
BackgroundPolycystic ovary syndrome (PCOS) is a complex, multifactor disorder in women of reproductive age worldwide. Although RNA editing may contribute to a variety of diseases, its role in PCOS remains unclear.MethodsA discovery RNA-Seq dataset was obtained from the NCBI Gene Expression Omnibus database of granulosa cells from women with PCOS and women without PCOS (controls). A validation RNA-Seq dataset downloaded from the European Nucleotide Archive Databank was used to validate differential editing. Transcriptome-wide investigation was conducted to analyze adenosine-to-inosine (A-to-I) RNA editing in PCOS and control samples.ResultsA total of 17,395 high-confidence A-to-I RNA editing sites were identified in 3,644 genes in all GC samples. As for differential RNA editing, there were 545 differential RNA editing (DRE) sites in 259 genes with Nucleoporin 43 (NUP43), Retinoblastoma Binding Protein 4 (RBBP4), and leckstrin homology-like domain family A member 1 (PHLDA) showing the most significant three 3′-untranslated region (3′UTR) editing. Furthermore, we identified 20 DRE sites that demonstrated a significant correlation between editing levels and gene expression levels. Notably, MIR193b-365a Host Gene (MIR193BHG) and Hook Microtubule Tethering Protein 3 (HOOK3) exhibited significant differential expression between PCOS and controls. Functional enrichment analysis showed that these 259 differentially edited genes were mainly related to apoptosis and necroptosis pathways. RNA binding protein (RBP) analysis revealed that RNA Binding Motif Protein 45 (RBM45) was predicted as the most frequent RBP binding with RNA editing sites. Additionally, we observed a correlation between editing levels of differential editing sites and the expression level of the RNA editing enzyme Adenosine Deaminase RNA Specific B1 (ADARB1). Moreover, the existence of 55 common differentially edited genes and nine differential editing sites were confirmed in the validation dataset.ConclusionOur current study highlighted the potential role of RNA editing in the pathophysiology of PCOS as an epigenetic process. These findings could provide valuable insights into the development of more targeted and effective treatment options for PCOS.
Diseases of the endocrine glands. Clinical endocrinology
Hana Anindya Indana, Ira Puspitawati, Dyah Samti Mayasari
et al.
Objectives. This research aims to investigate whether there is an association between acute hyperglycemia and diabetes mellitus and the amount of circulating platelet-derived microparticles (PDMPs) during acute myocardial infarction (AMI) initial episode.
Methodology. This was a cross-sectional study. Subjects were AMI patients underwent hospitalization. Demography and clinical data were obtained from hospital records. Diabetes mellitus was defined from history of disease, antidiabetic use and/or level of HbA1C ≥6.5%. Levels of HbA1c, admission random and fasting blood glucose levels were measured in hospital laboratory. The PDMPs was measured by flow-cytometry method, by tagging with CD-41 FITC and CD-62 PE markers and threshold size of <1 µm, from venous blood. The circulating PDMPs amount was compared according to glucometabolic state, namely acute hyperglycemia (admission random glucose ≥200 mg/dL and fasting glucose ≥140 mg/dL) and diabetes mellitus. The comparative analysis between group was conducted with Student T tests or Mann-Whitney tests, where applicable.
Results. A total of 108 subjects were included and their data analyzed. Circulating PDMPs amount was significantly lower in subjects with admission random glucose ≥200 mg/dL as compared to those with below level (median (interquartile range (IQR)): 2,710.0 (718.0-8,167.0) count/mL vs. 4,452.0 (2,128.5-14,499.8) count/mL, p=0.05) and in subjects with fasting glucose ≥140 mg/dL as compared to those with below level (median (IQR): 2,382.0 (779.0-6,619.0) count/mL vs. 5,972.0 (2,345.7-14,781.3) count/mL, p=0.006). Circulating PDMPs amount was also significantly lower in diabetes mellitus as compared to non diabetic (median (IQR): 2,655.0 (840.0-5,821.0) count/mL vs. 4,562.0 (2,128.5-15,055.8) count/mL; p=0.007).
Conclusion. Acute hyperglycemia and diabetes mellitus significantly associated with lower amount of circulating PDMPs during the initial episode of AMI.
Diseases of the endocrine glands. Clinical endocrinology
Magaly Perez-Nieves, Jingwen Liu, Beth Mitchell
et al.
Introduction Fear of hypoglycemia (FoH) affects quality of life, emotional well-being, and diabetes management among people with type 1 diabetes (PwT1D). American Diabetes Association’s (ADA) guidelines recommend assessing FoH in clinical practice. However, existing FoH measures are commonly used in research and not in clinical practice. In this study, prevalence of FoH was assessed in PwT1D using a newly developed FoH screener for clinical practice; its association with established measures and outcomes was also determined. In addition, healthcare providers’ (HCPs) perspectives on implementing FoH screener into real-world practice were explored.Research design and methods This multiphase observational study used mixed methods in two phases. First, we collected a cross-sectional survey (including the screener) from PwT1D (≥18 years) from T1D Exchange Quality Improvement Collaborative adult clinics. Pearson correlations and regression analyses were performed on diabetes outcome measures using screener scores. Second, we conducted focus groups among HCPs who treat PwT1D and descriptive analysis to summarize results.Results We included 553 PwT1D. Participants had a mean±SD age of 38.9±14.2 years and 30% reported a high FoH total score. Regression analyses showed that higher A1c and higher number of comorbidities were significantly associated with high FoH (p<0.001). High FoH worry and behavior scores were significantly associated with 8-Item Patient Health Questionnaire and 7-Item Generalized Anxiety Disorder Scale scores. Participants with ≥1 severe hypoglycemia event(s) and impaired awareness of hypoglycemia had higher odds of high FoH. Eleven HCPs participated in focus group interviews; they expressed that the FoH screener is clinically necessary and relevant but poses implementation challenges that must be addressed.Conclusions Our results demonstrate FoH is common in PwT1D and affects their psychosocial well-being and diabetes management. In alignment with ADA position statement, HCP focus group results emphasize importance of screening for FoH. Implementing this newly developed FoH screener may help HCPs identify FoH in PwT1D.
Diseases of the endocrine glands. Clinical endocrinology
Objective: This study evaluated the efficacy of antithyroid drugs (ATDs) and risk factors associated with the recurrence of Graves’ hyperthyroidism using a comprehensive retrospective cohort.
Methods: We included 1829 patients newly diagnosed with Graves’ hyperthyroidism, with sufficient follow-up data. Clinical outcomes of the patients and risk factors associated with recurrence-free survival, including the changes in thyrotropin receptor antibody, were evaluated.
Results: The median age of the patients was 44.5 years, and 69% were female. Among the patients, 1235 had a chance to withdraw ATD after a median of 23 (interquartile range (IQR) 17.0–35.5) months of treatment. The first remission rate was 55.6% during a median of 72.7 months of follow-up. After the first recurrence, 95% of patients underwent the second course of ATD treatment for a median of 21 .1 (IQR 14.8–31.7) months, and the remission rate was 54.1%. During a median of 67 months of follow-up, 7.7% of patients underwent surgery, and 10.5% underwent radioac tive iodine therapy. Approximately 30% were still on ATD therapy for recurrent disease or prolonged lowdose maintenance. Younger age (<45 years), male sex, and fluctua ting or smoldering of TRAb levels were independent risk factors of the first recurrenc e after ATD treatment.
Conclusions: ATD treatment is an acceptable option for the initial treatment of Graves’ hyperthyroidism as well as for recurrent disease. The optimal treatment period for ATD treatment needs to be determined using the individual risk factors of recurrence.
Diseases of the endocrine glands. Clinical endocrinology
Chisaka Kuehnemann, Chisaka Kuehnemann, Kang-Quan Hu
et al.
Cellular senescence is a stress or damage response by which a cell adopts of state of essentially permanent proliferative arrest, coupled to the secretion of a number of biologically active molecules. This senescence-associated secretory phenotype (SASP) underlies many of the degenerative and regenerative aspects of cellular senescence - including promoting wound healing and development, but also driving diabetes and multiple age-associated diseases. We find that nicotinamide phosphoribosyltransferase (NAMPT), which catalyzes the rate-limiting step in nicotinamide adenine dinucleotide (NAD) biosynthesis, is elevated in senescent cells without a commensurate increase in NAD levels. This elevation is distinct from the acute DNA damage response, in which NAD is depleted, and recovery of NAD by NAMPT elevation is AMPK-activated protein kinase (AMPK)-dependent. Instead, we find that senescent cells release extracellular NAMPT (eNAMPT) as part of the SASP. eNAMPT has been reported to be released as a catalytically active extracellular vesicle-contained dimer that promotes NAD increases in other cells and extends lifespan, and also as free monomer that acts as a damage-associated molecular pattern and promotes conditions such as diabetes and fibrosis. Senescent cells released eNAMPT as dimer, but surprisingly eNAMPT appeared in the soluble secretome while being depleted from exosomes. Finally, diabetic mice showed elevated levels of eNAMPT, and this was lowered by treatment with the senolytic drug, ABT-263. Together, these data reveal a new SASP factor with implications for NAD metabolism.
Diseases of the endocrine glands. Clinical endocrinology
Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.
Diseases of the endocrine glands. Clinical endocrinology
Chaitanya K. Mamillapalli, Jessi R. Prentice, Arvind K. Garg
et al.
Purpose: Adherence rates to published guidelines for diabetic retinopathy (DR) screening is between 35 and 60%. We evaluate a teleretinal DR screening (TDRS) program in a private practice vertically integrated system to increase compliance with retinal screening. Methods: A retrospective pre-post intervention longitudinal study was conducted in a private endocrinology practice using TDRS as the primary intervention. Compliance rates for diabetic retinal screening were compared between December 31, 2016 and December 31, 2018. Results: A total population of 3479 patients were evaluated. Retinal screening compliance improved from 56.5% of patients (1964) pre-intervention to 59.3% of patients (2064) post intervention. The McNemar test was used for statistical analysis and found the change significant (p = 0.004). Conclusions: TDRS as an adjunct tool in a private practice endocrinology office significantly improved screening rates and can increase access to recommended diabetic eye care. However, the improvement in screening rates was smaller than other types of practice settings. We explore some of the unique challenges to implementation of TDRS in private practice settings. Keywords: Diabetes, Diabetic macular edema, Diabetic retinopathy, Diabetic screening, Telemedicine, Teleretinal
Diseases of the endocrine glands. Clinical endocrinology
Objectives. The aim was to investigate neutrophil gelatinase-associated lipocalin (NGAL) levels in the serum and term placentas and its potential role in gestational diabetes mellitus (GDM). Methods. A total of 49 GDM subjects and 39 age-matched women with normal pregnancies were recruited. We examined serum concentrations of NGAL and tumor necrosis factor-α (TNF-α) in maternal blood and cord blood and their expression levels in the term placentas and umbilical cord. Results. Serum NGAL levels were significantly higher in GDM patients than in normal pregnant controls both in the maternal blood (4.80 ± 1.99 vs. 3.66 ± 1.13, P=0.001) and the cord blood (4.70 ± 2.08 vs. 3.85 ± 1.44, P=0.027). Moreover, serum NGAL levels exhibited a positive correlation with various parameters of insulin resistance. Maternal serum NGAL levels positively correlated with the NGAL levels found in the cord blood of the control (r = 0.399, P=0.012) and the GDM subjects (r = 0.349, P=0.014). Finally, the expression of NGAL protein levels in the placenta (1.22 ± 0.39 vs. 0.65 ± 0.23, P<0.001) and umbilical cord (0.65 ± 0.23 vs. 0.25 ± 0.10, P<0.001) were higher in GDM women than those noted in the control subjects. In the GDM group, maternal serum NGAL levels exhibited a positive correlation with placental NGAL mRNA and protein levels (r = 0.848, P=0.008; r = 0.636, P=0.011, respectively). Conclusions. NGAL may be an important adipokine involved in GDM and fetal development. The oversecretion of NGAL from the placenta may contribute to the elevated levels of serum NGAL in gestational diabetes mellitus.
Diseases of the endocrine glands. Clinical endocrinology
Guillermo Dieuzeide, Luis De Loredo, Natalia Pugnaloni
et al.
Introduction: The CAPTURE study estimated the contemporary (2019) prevalence of cardiovascular disease (CVD) in people with type 2 diabetes (T2D) across 13 countries. This CAPTURE post hoc analysis describes the occurrence of chronic kidney disease (CKD) in the group with and without CVD in Argentinian population.
Methods: CAPTURE is a multinational, cross-sectional, non-interventional study conducted between December 2018 and September 2019. Data on CVD diagnoses, estimated glomerular filtration rate (eGFR) and urine albumin level was collected during routine visits. CKD was assessed in the subjects with and without CVD.
Nutritional diseases. Deficiency diseases, Diseases of the endocrine glands. Clinical endocrinology
Tomoya Uchimura, Seiji Hara, Takashi Yazawa
et al.
Medaka (Oryzias latipes) are teleost fish with a XX/XY sex determination system. Recently, it was reported that high temperature (HT) induced the masculinization of XX medaka by increasing the levels of cortisol, a major glucocorticoid produced by interrenal cells in teleosts. Cortisol secretion is regulated by adrenocorticotropic hormone (ACTH) secreted from the pituitary gland, which is partly regulated by corticotropin-releasing hormone (CRH) secreted from the hypothalamus. In teleosts, two crh paralogs, named crha and crhb, have been identified. Recently, the expression of crhb but not crha was upregulated by HT during gonadal sex differentiation period in medaka and loss-of-functions of its receptors under HT suppressed masculinization of XX medaka and increase of cortisol levels, suggesting that crhb is involved in masculinization induced by HT. However, the transcriptional regulation of crhb under HT has not been elucidated. We analyzed the gene expression pattern in the hypothalamus of medaka embryos incubated under HT using DNA microarray. The expressions of heat shock protein (hsp) genes, such as hsp70.1 and hsp30, were increased. Overexpression of hsp70.1 or hsp30 in cultured rat hypothalamic 4B cells significantly induced crh gene expression. Moreover, hypothalamic hsp70.1-overexpressing transgenic medaka also showed increased crhb gene expression that increased cortisol levels compared with fish incubated at a normal temperature. These results provide the first evidence that HSPs induce cortisol levels by elevating crhb gene expression in the hypothalamus.
Diseases of the endocrine glands. Clinical endocrinology
Jairo Bustamante B., Iván Molina V., Fernando Cardona A.
et al.
Fragmento
En el presente estudio se hace una revisión de los aspectos clínicos y citológicos de 16 casos de disgenesia gonadal estudiados en los Departamentos de Medicina Interna, Ginecología y Pediatría del Hospital Universitario San Vicente de Paúl de Medellín en los años 1967 y 1968.
Diseases of the endocrine glands. Clinical endocrinology