While the relationship between obesity and reproductive dysfunction is well known, the physiological mechanism behind obesity-related infertility remains unclear. Previous work suggests that follicle development prior to...While the relationship between obesity and reproductive dysfunction is well known, the physiological mechanism behind obesity-related infertility remains unclear. Previous work suggests that follicle development prior to ovulation is disrupted in obese individuals. Follicle-stimulating hormone (FSH) and anti-Mullerian hormone (AMH) are two key regulators of follicle development, and the poorest reproductive outcomes have been recorded when these hormones are imbalanced. In order to understand how obesity impacts the reproductive axis, the present study induces reproductive dysfunction in female rats using a high-fat, high-sugar diet (HFHS). In our study, several animals on the HFHS diet displayed abnormal estrous cycles. The HFHS diet also resulted in an increased prevalence of ovarian cysts and decreased formation of corpora lutea. Across all groups, the FSH/AMH ratio displayed a strong negative correlation with pre-antral, antral, and total follicle counts. Moreover, rats on the HFHS diet displayed larger adipocytes and produced higher levels of leptin than controls. When combined with average adipocyte size in multiple regression, the FSH/AMH ratio was strongly associated with cyst formation in the ovary. These findings provide strong evidence for the potential relevance of a combined FSH/AMH ratio as a marker of ovarian health and follicular status. Therefore, this ratio reflects a complex interaction between the reproductive and metabolic systems.
: Sodium-glucose cotransporter (SGLT) 2 is responsible for most of the glucose reabsorption in the kidneys and has been proposed as a novel therapeutic target for the treatment of type 2 diabetes. In recent years, nonalc...: Sodium-glucose cotransporter (SGLT) 2 is responsible for most of the glucose reabsorption in the kidneys and has been proposed as a novel therapeutic target for the treatment of type 2 diabetes. In recent years, nonalcoholic steatohepatitis (NASH), the pathogenesis of which is strongly associated with insulin resistance, obesity, and type 2 diabetes, has become a considerable healthcare burden worldwide. However, there is currently no established pharmacotherapy for NASH. Here, we investigated the therapeutic effects of the SGLT2 selective inhibitor ipragliflozin alone and in combination with metformin on NASH in high fat and cholesterol diet-fed KK/A type 2 diabetic mice.: This diabetic model had hyperglycemia, insulin resistance, and obesity, and also exhibited steatosis, inflammation, and fibrosis in the liver, pathological features resembling those in human NASH. Four-week repeated administration of ipragliflozin significantly improved not only hyperglycemia, insulin resistance, and obesity but also hyperlipidemia and NASH-associated symptoms including hepatic steatosis and fibrosis. In addition, ipragliflozin attenuated inflammation and oxidative stress in the liver. Repeated administration of metformin also significantly improved symptoms of type 2 diabetes with NASH to a comparable degree to that by ipragliflozin. In addition, combination treatment with ipragliflozin and metformin additively improved these symptoms.: These results demonstrate that the SGLT2 selective inhibitor ipragliflozin improves not only hyperglycemia but also NASH in type 2 diabetic mice, suggesting that treatment with ipragliflozin alone and in combination with metformin may be effective for treating type 2 diabetes with NASH.
: This study aimed to evaluate the association between thyroid parameters and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).: In this cross-sectional study, a total of 911 euthyroid...: This study aimed to evaluate the association between thyroid parameters and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).: In this cross-sectional study, a total of 911 euthyroid patients with T2DM (539 men and 372 women; mean age, 60.81 ± 12.93 years) were enrolled. Clinical factors were assessed and free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels were measured. DR was diagnosed using fundus fluorescein angiography.: Compared with patients without DR (n = 718), patients with DR (n = 193) exhibited lower FT3 (4.40 ± 0.58 vs. 4.50 ± 0.51 pmol/L; = .019) and FT4 (14.86 ± 2.09 vs. 15.91 ± 2.18 pmol/L; < .001) and higher TSH (1.86 [1.22, 2.66] vs. 1.58 [1.14, 2.34] µIU/mL; = .015) levels. After adjustment for potential DR risk factors, patients in the highest tertile of plasma FT4 levels had a 0.332-fold likelihood of developing DR compared with those in the lowest tertile of plasma FT4 levels (P < 0.001). The prevalence of DR showed a significantly decreasing trend across the three tertiles based on FT4 levels (31.35%, 19.08% and 13.16%; P < 0.001). Similar results were obtained for the presence of proliferative DR.: These findings suggest that low-normal FT4 levels are associated with the prevalence of DR in euthyroid patients with T2DM.
: Transthyretin (TTR) is a protein with a growing number of biological functions in addition to its well-established binding and circulatory transport of thyroxine, and indirect retinoid transport through interaction wit...: Transthyretin (TTR) is a protein with a growing number of biological functions in addition to its well-established binding and circulatory transport of thyroxine, and indirect retinoid transport through interaction with retinol-binding protein. Misfolded and aggregated wild-type and mutant TTRs are involved in amyloid diseases. Several aspects of TTR pathology and physiology remain poorly understood. Receptor-mediated cellular transport of TTR has been described in a few cell types; and such studies suggest the possibility of different TTR receptors and endocytic pathways. Our main objective was to further understand the endocytic pathways for TTR.: In the current study, analyses of TTR endocytic transport were performed in the human A431 cell line. The results of TTR uptake were compared with those of the iron-carrier protein transferrin (Tf, a common stardard for endocytosis studies) in the same cell types.: A comparison of TTR and Tf endocytosis suggested similar early, 5-10 min, accumulation kinetics. But at a later time, 30 min, TTR accumulation was 20-30% lower than that of Tf ( < .05), a result that suggests different post-endocytic fates for these two ligands. Through the use of multiple endocytosis inhibitors, biochemical evidence is provided for an internalization pathway that differs from the clathrin-mediated endocytosis of Tf.: These results for A431 cells are compared with others reported for different cell types; and it is suggested that this same hormone carrier protein can transit into cells through multiple endocytic pathways.
: In this study, we aimed to evaluate ABO blood groups and Rh factor in patients with thyroid cancer.: Demographical and clinical features, cytological results, ABO blood groups, and Rh factor status of patients with ben...: In this study, we aimed to evaluate ABO blood groups and Rh factor in patients with thyroid cancer.: Demographical and clinical features, cytological results, ABO blood groups, and Rh factor status of patients with benign and malignant thyroid disease were evaluated. Histopathological features of thyroid cancer were compared in Rh positive and negative patients, and patients with different ABO blood groups.: Histopathological diagnosis was benign in 1,299 (63.5%) and malignant in 744 (36.5%) patients. There was no significant difference between benign and malignant patients in terms of age, sex, thyroid autoantibody positivity, and ABO blood groups ( > .05 for each). A significantly higher rate of patients with malignant disease were Rh positive compared to patients with benign disease (91.8% vs. 88.1%, = .046). In thyroid cancer patients, extrathyroidal extension and advanced stage (3-4) were observed more frequently in patients with B compared to non-B blood groups ( = .028 and 0.042, respectively). The likelihood of the extrathyroidal extension was 4.272 (95%: 1.816-10.049) times higher in B blood group compared to non-B blood groups in patients with multifocal disease ( < .001). Patients with O blood group had lower rate of capsular invasion than patients with non-O blood groups ( = .018).: Patients with B blood group had higher risk of extrathyroidal extension and advanced stage compared to patients with non-B blood group.
Petrica L, Pusztai AM, Vlad M
… +17 more, Vlad A, Gadalean F, Dumitrascu V, Vlad D, Velciov S, Gluhovschi C, Bob F, Ursoniu S, Petrica M, Matusz P, Cretu O, Radu D, Milas O, Secara A, Simulescu A, Popescu R, Jianu DC
: The association of vascular remodeling in the kidney and the brain with a particular microRNAs (miRNA) profile is not well studied.: Seventy-six patients with Type 2 diabetes and 11 healthy subjects were assessed conce...: The association of vascular remodeling in the kidney and the brain with a particular microRNAs (miRNA) profile is not well studied.: Seventy-six patients with Type 2 diabetes and 11 healthy subjects were assessed concerning urine albumin: creatinine ratio (UACR), biomarkers of podocyte injury and of proximal tubule (PT) dysfunction. MiRNA were quantified in blood and urine by a real-time PCR System. Cerebrovascular ultrasound measurements were performed in the carotid and middle cerebral arteries.: MiRNA21 and miRNA124 correlated positively with nephrin, podocalyxin, synaptopodin, urinary N-acetyl-D-glucosaminidase (NAG), urinary kidney-injury molecule-1 (KIM-1), UACR, and negatively with eGFR; miRNA125a, 126, 146a, 192 correlated negatively with nephrin, podocalyxin, synaptopodin, urinary NAG, urinary KIM-1, UACR, and directly with eGFR. Plasma miRNA-21 and miRNA192 correlated directly with cerebral hemodynamics parameters of atherosclerosis and arteriosclerosis. MiRNA-124, 125a, 126, 146a showed negative correlations with the same parameters.: In Type 2 diabetes patients there is an association of vascular remodeling in the brain and the kidney with a specific miRNAs pattern. Cerebrovascular changes occur even in normoalbuminuric patients, with 'high-to-normal' levels of podocyte injury and PT dysfunction biomarkers. These phenomena may be explained by the variability of miRNA expression within the two organs in early DKD.
: Recent reports show that girls with higher body mass index (BMI) have an earlier puberty onset (thelarche). It has been suggested that earlier puberty is a consequence of higher levels of estrogen due to increased arom...: Recent reports show that girls with higher body mass index (BMI) have an earlier puberty onset (thelarche). It has been suggested that earlier puberty is a consequence of higher levels of estrogen due to increased aromatization of androgens in adipose tissue. Thus, we aimed to assess the relation between serum levels of estrogen and excess weight (BMI ≥1SD) and central adiposity (>75th percentile for waist circumference) in prepubertal girls at age 7.: We conducted a cross-sectional study within the Growth and Obesity Cohort Study of 1190 low-middle income children from Santiago, Chile. We selected a random sample of 107 prepubertal girls at age 7. A trained dietitian measured weight, height and waist circumference. Additionally, a fasting blood sample was collected to measure serum levels of estradiol equivalents (via ultrasensitive recombinant cell bioassay), dehydroepiandrosterone sulfate (DHEAS), insulin, insulin-like growth factor 1 (IGF-1), and leptin.: Excess weight was observed in 40% of our sample; 11.2% had high central adiposity, and the mean level of estradiol equivalents was 3.6 ± 2.3 pg/ml. In the univariate and multivariate analyzes, we did not observe an association between excess weight, central adiposity and estradiol equivalent levels; however, insulin was inversely associated with the serum level of estradiol equivalents.: Our participants had a mean level of estradiol equivalents of 3.6 pg/ml (±2.3 pg/ml) at the pre-pubertal stage. However, with the exception of insulin, we did not observe an association between estradiol equivalents and markers of adiposity and metabolic and hormonal factors.
Estrogen (E2) modulates a wide range of neural functions such as spine formation, synaptic plasticity, and neurotransmission in the hippocampus. Dendritic spines and synapse numbers in hippocampal neurons of female rats...Estrogen (E2) modulates a wide range of neural functions such as spine formation, synaptic plasticity, and neurotransmission in the hippocampus. Dendritic spines and synapse numbers in hippocampal neurons of female rats cyclically fluctuate across the estrous cycle, but the key genes responsible for these fluctuations are still unknown. In order to address this question, we explore the hippocampal transcriptome via RNA-sequencing (RNA-seq) at the proestrus () and estrus () stages in female rats. At standard fold-change selection criteria, 37 differentially expressed genes () were found in PE vs. ES groups (FDR adjusted -value (q)<0.05). The transcriptional changes identified by RNA-seq were confirmed by quantitative real-time PCR. To gain insight into the function of the DEGs, the E2-regulated genes were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database (KEGG). Based on GO and KEGG pathways, the identified DEGs of PE vs. ES stages are involved in extracellular matrix formation, regulation of actin cytoskeleton, oxidative stress, neuroprotection, immune system, oligodendrocyte maturation and myelination, signal transduction pathways, growth factor signaling, retinoid signaling, aging, cellular process, metabolism and transport. The profiles of the gene expression in the hippocampus identified at the PE vs. ES stages were compared with the gene expression profiles in ovariectomized (OVX) rats receiving E2 replacement via RNA-seq and qPCR. The profiles of gene expression between the OVX+E2 and the estrous cycle were different and the possible causes were discussed.
We have shown that non-sulfated cholecystokinin-8 (NS CCK-8) reduces food intake in adult male Sprague Dawley rats by activating cholecystokinin-B receptor (CCK-BR). Here, we tested the hypothesis that the vagus nerve an...We have shown that non-sulfated cholecystokinin-8 (NS CCK-8) reduces food intake in adult male Sprague Dawley rats by activating cholecystokinin-B receptor (CCK-BR). Here, we tested the hypothesis that the vagus nerve and the celiaco-mesenteric ganglia may play a role in this reduction. The hypothesis stems from the following facts. The vagus and the celiaco-mesenteric ganglia contain NS CCK-8, they express and have binding sites for CCK-BR, NS CCK-8 activates CCK-BR on afferent vagal and sympathetic fibers and the two structures link the gastrointestinal tract to central feeding nuclei in the brain, which also contain the peptide and CCK-BR. To test this hypothesis, three groups of free-feeding rats, vagotomy (VGX), celiaco-mesenteric ganglionectomy (CMGX) and sham-operated, received NS CCK-8 (0, 0.5 and 1 nmol/kg) intraperitoneally prior to the onset of the dark cycle and various feeding behaviors were recorded. We found that in sham-operated rats both doses of NS CCK-8 reduced meal size (MS), prolonged the intermeal interval (IMI, time between first and second meal), increased satiety ratio (SR = IMI/MS), reduced 24-h food intake and reduced the number of meals relative to saline control. In the VGX and the CMGX groups, all of the previous responses were attenuated. Consistent with our hypothesis, the findings of the current work suggest a role for the vagus nerve and the celiaco-mesenteric ganglia in the feeding responses evoked by NS CCK-8.
: Being born with low birth weight (LBW) is a risk factor for muscle insulin resistance and type 2 diabetes (T2D), which may be mediated by epigenetic mechanisms programmed by the intrauterine environment. Epigenetic mec...: Being born with low birth weight (LBW) is a risk factor for muscle insulin resistance and type 2 diabetes (T2D), which may be mediated by epigenetic mechanisms programmed by the intrauterine environment. Epigenetic mechanisms exert their prime effects in developing cells. We hypothesized that muscle insulin resistance in LBW subjects may be due to early differential epigenomic and transcriptomic alterations in their immature muscle progenitor cells.: Muscle progenitor cells were obtained from 23 healthy young adult men born at term with LBW, and 15 BMI-matched normal birth weight (NBW) controls. The cells were subsequently cultured and differentiated into myotubes. DNA and RNA were harvested before and after differentiation for genome-wide DNA methylation and RNA expression measurements.After correcting for multiple comparisons (q ≤ 0.05), 56 CpG sites were found to be significantly, differentially methylated in myoblasts from LBW compared with NBW men, of which the top five gene-annotated CpG sites () previously have been associated to regulation of cholesterol, fatty acid and glucose metabolism and muscle development or hypertrophy. LBW men displayed markedly decreased myotube gene expression levels of the AMPK-repressing tyrosine kinase gene and the histone deacetylase gene . Silencing of and was associated with impaired myotube formation, which for reduced muscle glucose uptake.: The data provides evidence of impaired muscle development predisposing LBW individuals to T2D is linked to and potentially caused by distinct DNA methylation and transcriptional changes including down regulation of and in their immature myoblast stem cells.
: Testotoxicosis is an autosomal dominant form of limited gonadotropin-independent precocious puberty in boys. It is caused by a heterozygous constitutively activating mutation of the gene encoding the luteinizing/hormo...: Testotoxicosis is an autosomal dominant form of limited gonadotropin-independent precocious puberty in boys. It is caused by a heterozygous constitutively activating mutation of the gene encoding the luteinizing/hormone receptor (LHR). Some twenty mutations of the gene have been reported. Most of them are constitutive mutations isolated from blood leukocyte DNA, although others are somatic, found only in testicular tumoural tissue. In all the previously reported cases of these somatic mutations, the tumour, whether a nodular Leydig cell adenoma or hyperplasia, was easily visible on testicular ultrasonography. The aim of this study was to describe an unusual presentation of a patient with the clinical and hormonal characteristics of testotoxicosis but no well-circumscribed lesion at testicular ultrasonography.: Molecular analysis of the gene was performed by direct sequencing of DNA extracted from peripheral leucocytes and testicular biopsy.: Molecular analysis didn't find any LHR mutation in blood, whereas it revealed for the first time a somatic D578H mutation in testicular tissue despite no evidence of a nodular aspect at testis ultrasonography.: This observation underlines the need to look for a somatic gene mutation from the testicular biopsies of all boys with testotoxicosis with no constitutive gene mutation identified from blood DNA, even in the absence of circumscribed testicular lesion at ultrasonography. In addition, based on the known link between LHR mutations and testicular tumourigenesis, yearly ultrasound monitoring of the testes should be considered for these patients.
: Evidence has shown that low thyroid hormone levels may lead to worse prognosis including a higher mortality rate in patients with heart failure (HF). Thyroid replacement increases cardiac output and exercise performanc...: Evidence has shown that low thyroid hormone levels may lead to worse prognosis including a higher mortality rate in patients with heart failure (HF). Thyroid replacement increases cardiac output and exercise performance without causing significant adverse events. The purpose of this study is to compare levothyroxine doses in patients with and without HF.: This single center, retrospective cohort study compared levothyroxine doses in ambulatory hypothyroid patients with a history of HF to those without a history of HF. Patients were stratified into three groups: no HF, HF with reduced ejection fraction (HFrEF, EF<40%), and other types of HF. The primary endpoint of average levothyroxine dose was analyzed using multivariable linear regression with variables determined .: Three hundred patients were included in the study with 100 patients in each arm. Average levothyroxine doses (mcg/kg) were 1.5 ± 0.7, 1.6 ± 0.8, and 1.6 ± 0.9 for no HF, other types of HF, HFrEF, respectively (= .61). Factors found to be significantly related to levothyroxine dosing included gender, drug-drug interactions, and the timing of clinic visit to lab draw. No differences were found in secondary outcomes including TSH levels, free T, T, and percentage of patients with elevated thyroid-stimulating hormone (TSH) among HFrEF, other types of HF, and no HF patients. Among HF patients, average ejection fractions were also similar comparing patients with elevated TSH, normal TSH, and low TSH.: The dose of levothyroxine was not significantly different in HF patients compared to patients without HF.
: The association of subclinical thyroid dysfunction (SCTD) with chronic kidney disease (CKD) among community population remains inconclusive. Our aim was to evaluate the association between SCTD and the risk of CKD by c...: The association of subclinical thyroid dysfunction (SCTD) with chronic kidney disease (CKD) among community population remains inconclusive. Our aim was to evaluate the association between SCTD and the risk of CKD by conducting a meta-analysis.: Multiple databases were searched to identify studies on the association between SCTD and risk of CKD, up to October 2018. Relevant information for analysis was extracted. A random-effects model was used to calculate the pooled risk estimate.: Eight articles were included in this meta-analysis, with three cohort and five cross-sectional studies. The pooled odds ratio (OR) of subclinical hypothyroidism for CKD was 1.37 (95% CI: 1.13-1.67, = .000, n = 8) in a multivariable-adjusted model. A significant association was observed in subgroup younger than 70 years (OR = 1.40, 95% CI: 1.09-1.79, = .000, n = 6), but not in subgroup older than 70 years (OR = 1.28, 95% CI: 0.89-1.83, = .186, n = 2). For subclinical hyperthyroidism, the summary OR was 1.16 (95%CI: 0.97-1.39, = .115, n = 5) and subgroup analyses by age and study design did not alter the results significantly.: Our findings demonstrated that subclinical hypothyroidism was significantly associated with a higher risk of CKD independent of some conventional risk factors among community population and age might have modifying effects on the association.
: We aimed to compare the thyroid ultrasonographic findings of severely obese nonobese individuals, and the frequency, characteristics, and risk of malignancy in detected nodules.: Case-control study including 67 adults...: We aimed to compare the thyroid ultrasonographic findings of severely obese nonobese individuals, and the frequency, characteristics, and risk of malignancy in detected nodules.: Case-control study including 67 adults with severe obesity (body mass index [BMI] ≥ 35 kg/m) and 67 nonobese controls (BMI < 30 kg/m). The participants underwent ultrasound evaluation of the thyroid and cervical subcutaneous tissue. The risk of malignancy in detected nodules was determined using the American Thyroid Association (ATA) 2015 and the Thyroid Imaging Reporting and Data System (TI-RADS) classifications. Fine-needle aspiration biopsy (FNAB) was performed in nodules for which the procedure was recommended according to the ATA-2015 or TI-RADS criteria, and the cytological evaluation followed the Bethesda classification.: The mean BMI values in the case and control groups were 47.0 ± 6.1 kg/m and 22.8 ± 2.7 kg/m, respectively. There were no differences between groups regarding sex, age, total T3, and antiperoxidase (antiTPO) antibody positivity. When compared with controls, severely obese individuals showed a greater frequency of parenchymal hypoechogenicity (p = 0.042), cervical subcutaneous tissue thickness (p < 0.001), overall frequency of thyroid nodules (p = 0.038), and frequency of multiple nodules (p = 0.013). No significant differences were observed in terms of risk of nodular malignancy according to both the ATA-2015 and TI-RADS classifications in severely obese compared with nonobese individuals.: Severely obese individuals ( nonobese controls) presented increased parenchymal hypoechogenicity and frequency of thyroid nodules on ultrasonographic evaluation. However, no significant differences were observed in terms of risk of nodular malignancy between both groups according to the ATA-2015 and TI-RADS criteria. Thus, ultrasonographic thyroid screening of severely obese individuals is not justified.
: So far no research concerning the omentin-1 ( rs2274907 and vaspin ( rs2236242 polymorphisms has been carried out in a healthy pediatric population. We analyzed associations of these polymorphisms with anthropometric p...: So far no research concerning the omentin-1 ( rs2274907 and vaspin ( rs2236242 polymorphisms has been carried out in a healthy pediatric population. We analyzed associations of these polymorphisms with anthropometric parameters, lipid profile, as well as adiponectin, leptin and soluble leptin receptor (sOB-R) levels in prepubertal healthy children, to search for their possible role in the risk of obesity and obesity-related disorders.: Frequencies of these polymorphisms were analyzed by the restriction fragment length polymorphism in 89 normal-weight children. The body composition was measured by dual-energy X-ray absorptiometry. Serum levels of adipokines were measured using ELISA methods.: We observed differences in values of HDL-cholesterol ( = 0.002) and triglycerides ( = 0.039) in children carrying different genotypes of the rs2274907 polymorphism. In children carrying different genotypes of the rs2236242 polymorphism differences in BMI ( =0.025) and BMI Z-score ( = 0.01) values were found. Significant relations between anthropometric parameters and levels of HDL-cholesterol and triglycerides were associated with minor alleles of the studied polymorphisms. In addition, leptin/sOB-R ratio was related to HDL-cholesterol ( = 0.004) and triglycerides ( = 0.03) levels in children carrying minor allele of the rs2236242 SNP.: We suggest that both rs2274907 and rs2236242 polymorphisms influence body composition and lipid profile in prepubertal healthy children. Relations between anthropometric parameters, lipid and adipokine levels may be associated with minor alleles of the studied polymorphisms. The possible role of these polymorphisms in the modulation of the risk of obesity and obesity-related disorders in the later life might be considered.
: To identify the sociodemographic and clinical characteristics related to the occurrence of diabetic ketoacidosis (DKA) and frequent hypoglycemia in children, adolescents and adults with type 1 diabetes in China.: The 3...: To identify the sociodemographic and clinical characteristics related to the occurrence of diabetic ketoacidosis (DKA) and frequent hypoglycemia in children, adolescents and adults with type 1 diabetes in China.: The 3C Study was an epidemiological study that recruited 849 type 1 diabetes patients aged 0-78 years in Beijing and Shantou, China. Separate logistic regression models were used to evaluate the association of sociodemographic and clinical factors with the occurrence of DKA in the past 12 months or frequent hypoglycemia (≥5 episodes) in the past 7 days.: Children and adolescents were significantly more likely to have DKA in the past 12 months compared to adults: odds ratio (OR) and (95% confidence interval [CI]), 4.67 (1.90, 11.52) for <13 years and 4.00 (1.59, 10.10) for 13 to <19 years. Underweight participants were also more likely to have DKA relative to normal weight participants: OR (95% CI), 6.87 (2.64, 17.87). Children and participants who did not receive diabetes education in the past 12 months were more likely to have frequent hypoglycemia: OR (95% CI), 2.95 (1.23, 7.06) and 7.67 (1.77, 13.2), respectively. Participants who reported self-monitoring of blood glucose ≤2 times/week (ref: 7 times/week) and participants who had higher HbA1c levels were less likely to have frequent hypoglycemia: OR (95% CI), 0.14 (0.03, 0.64) and 0.78 (0.63, 0.96), respectively. Gender, family income, parent education, health insurance coverage, diabetes duration, and insulin administration method were not significantly associated with DKA or frequent hypoglycemia in this sample.: Children, adolescents and underweight individuals with type 1 diabetes in China were more likely to report DKA, and children, individuals without adequate diabetes education, and those with lower HbA1c levels were more likely to have frequent hypoglycemia. These patients should be targeted for preventive interventions.
: Limited and contradictory data on the circulating levels of glucagon-like peptide (GLP-1) and resistin in hepatitis C virus genotype-4 (HCV-4) cirrhotic patients are present. Thus, this study aimed to evaluate their co...: Limited and contradictory data on the circulating levels of glucagon-like peptide (GLP-1) and resistin in hepatitis C virus genotype-4 (HCV-4) cirrhotic patients are present. Thus, this study aimed to evaluate their concentrations and to investigate the association between total GLP-1, resistin, and insulin resistance in those patients.: Non-diabetic HCV-4 cirrhotic patients (n = 80; 40 with Child-Pugh A, 20 with Child-Pugh B, and 20 with Child-Pugh C), and 25 healthy subjects were enrolled in this study. The basal circulating levels of total GLP-1 and resistin along with serum insulin, glucose, total cholesterol, and triglycerides were measured.: Plasma GLP-1 and serum resistin levels were significantly higher in cirrhotic patients than controls ( < . 001). Moreover, circulating GLP-1 and resistin levels increased in a stepwise fashion in line with increasing grade of liver damage. According to Spearman's rank correlation, both GLP-1 and resisitin correlated positively with each other, insulin, homeostatic model assessment of insulin resistance, alanine aminotransferase (ALT), total bilirubin, and international normalized ratio while they correlated negatively with albumin ( < .001). Multiple stepwise regression analysis showed that ALT, serum resistin and Child-Pugh score independently influenced the GLP-1 levels in cirrhotic patients.: Circulating levels of GLP-1 and resistin were elevated in cirrhotic patients with HCV-4. Further, the severity of liver cirrhosis and serum resistin were the determinant factors explaining the variability of GLP-1 levels by about 84%. In addition, a positive relation was found between insulin resistance and both GLP-1 and resistin levels.
: Earlier studies have linked lipid profile to osteoporotic fractures; however, to our knowledge, no study had summarized available data on this relationship. We aimed to summarize the current evidence on the association...: Earlier studies have linked lipid profile to osteoporotic fractures; however, to our knowledge, no study had summarized available data on this relationship. We aimed to summarize the current evidence on the association between lipid profile and bone fractures. : A systematic search of PubMed and Scopus was done to find relevant published studies until March 2018. To combine effect sizes, we applied fixed- or random-effects analysis, where appropriate. Cochran's Q test and were used to assess between-study heterogeneity. : Overall, 11 studies (seven prospective, three cross-sectional and one case-control studies) were included in the current systematic review. Out of them, 10 studies with a total sample size of 60,484 individuals, aged 25 years or more, were used in the meta-analysis. The results showed that total cholesterol concentration was positively associated with risk of bone fracture; such that a 50-mg/dl increase in plasma level of TC was associated with 15% greater odds of bone fracture (combined effect size: 1.15, 95% CI: 1.02-1.30, = .02). Furthermore, we found that individuals with a decreased level of HDL (<40 mg/dl) had a lower risk of bone fracture compared with those with a normal level (≥40 mg/dl) (combined effect size: 0.82, 95% CI: 0.71-0.96, = .01). No significant association was found between plasma level of TG and LDL with the risk of bone fractures either in prospective or cross-sectional studies. : We found that plasma levels of total cholesterol were positively associated with bone fractures. In addition, decreased levels of HDL were associated with an increased risk of osteoporotic fractures. : TG: triglycerides, TC: total cholesterol, HDL: high-density lipoprotein, LDL: low-density lipoprotein, OR: odds ratio, RR: relative risk, HR: hazard ratio, DXA: dual-energy X-ray absorptiometry, ICD: International Classification of Diseases, SD: standard deviation.
Graves' disease (GD) is a common organ-specific autoimmune disease, and its pathogenesis is still unclear. The aim of this study is to investigate the role of interleukin (IL)-21 in the regulation of Th17/Treg cells in G...Graves' disease (GD) is a common organ-specific autoimmune disease, and its pathogenesis is still unclear. The aim of this study is to investigate the role of interleukin (IL)-21 in the regulation of Th17/Treg cells in GD. We recruited 28 newly diagnosed GD patients, 27 GD patients in remission (eGD), and 24 normal controls (NC). Thyroid function and autoantibodies were evaluated by electrochemical luminescence. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured with or without recombinant human interleukin-21 (rhIL-21), and mRNA and protein levels were quantified by real-time PCR and ELISA, respectively. Compared with those in the eGD and control groups, the thyroid function indexes and autoantibodies levels were significantly different in the GD group ( < 0.05). Without rhIL-21 stimulation, the expression levels of retinoid-related orphan gamma t (RORγt), IL-17, IL-22, forkhead box protein P3 (Foxp3) and IL-10 mRNA and the IL-10 and IL-22 proteins were significantly higher in the GD group than those in the eGD and control groups ( < 0.05). rhIL-21 stimulation increased the RORγt, IL-17, and IL-22 mRNA levels and IL-22 protein levels and decreased the Foxp3 and IL-10 mRNA levels and IL-10 protein levels ( < 0.05) in the GD group. In conclusion, our analyses demonstrated that IL-21 might induce the differentiation of CD4 T cells to Th17 cells and reduce Treg cell differentiation, which could contribute to activation of the downstream immune response and the pathogenesis of GD.
Given that adipocytokines may play an important role in the pathophysiology of high blood pressure (HBP) and because related reports in children are scarce and controversial, we evaluated the relationship of leptin, resi...Given that adipocytokines may play an important role in the pathophysiology of high blood pressure (HBP) and because related reports in children are scarce and controversial, we evaluated the relationship of leptin, resistin, tumor necrosis factor-α, interleukin-6, adiponectin, and interferon-γ with HBP. . A total of 129 (53.8%) girls and 111 (46.2%) boys, with average ages of 10.8 ± 0.9 and 10.6 ± 1.0 years, respectively, were enrolled in a cross-sectional study. HBP was defined by systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) between the 90th and 95th percentiles. A multivariate logistic regression backwards-stepwise analysis adjusted for body mass index, waist circumference, and triglyceride levels was performed to compute the association between adipocytokines and HBP. . Seventy-two (30.0%) participants showed HBP: 44 (61.1%) girls and 28 (38.9%) boys. Multivariate analysis showed that, irrespective of obesity, serum levels of adiponectin, but not those of other adipocytokines, are inversely associated with HBP (odds ratio 0.93; 95% CI 0.77 to 0.98, p = .04). . Our results show that low serum adiponectin levels, but not those of other adipocytokines, are inversely associated with HBP; this association is independent of obesity.