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

Astrid Høj, Sonja Holm‐Yildiz, Thomas Krag et al.

ABSTRACT Multiple acyl‐CoA dehydrogenase deficiency (MADD) is a rare inborn metabolic myopathy affecting fat and protein metabolism. Patients with late‐onset MADD typically present with exercise intolerance and muscle weakness. We present a patient with an acute, very late‐onset symptom debut at 52 years of age. Over 5 months, the patient deteriorated from asymptomatic to almost complete loss of ambulation. He had a substantial weight loss, head‐drop, progressive proximal limb and chewing weakness. Due to the rapid progression, amyotrophic lateral sclerosis, myositis, myasthenia gravis and a paraneoplastic syndrome in relation to underlying malignancy were considered first. A 2‐[18F] FDG PET/CT scan was performed to exclude a paraneoplastic syndrome. The scan revealed diffuse and symmetric, pathologically high 2‐[18F] FDG‐uptake in the patient's neck, shoulder, and paravertebral muscles, which was later suggested as a sign of a metabolic myopathy. Muscle biopsy (Oil Red O staining) and acylcarnitine profile (elevated C5‐C18 acylcarnitines) findings suggested MADD, which was confirmed by genetic analysis showing biallelic variants in the ETFDH gene (c.1763A>G, p.(His588Arg); c.897G>A, p.(Leu299=)). After 1 month of dietary intervention and daily diet supplements (riboflavin 400 mg TID, levocarnitine 1 g TID, Q10 150 mg qD in two doses), the patient had almost recovered to his habitual level. A posttreatment muscle biopsy showed less disrupted ultrastructure of the myofibers. We learned from this case of rapid and late‐onset MADD that 2‐[18F] FDG PET/CT, with diffuse and symmetric 2‐[18F] FDG‐uptake in skeletal muscle, can be valuable in clarifying this rare diagnosis.

Qingsong Mao, Nianzhou Liu, Tian Xiong et al.

BackgroundThe association of the triglyceride glucose (TyG) index and related TyG metrics with obesity indices has been demonstrated to correlate with the incidence of cardiovascular disease (CVD). Nonetheless, this relationship has not been thoroughly investigated in patients with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3.MethodsThis study involved 7364 participants from the China Health and Retirement Longitudinal Study (CHARLS). Cox risk regression and restricted cubic spline (RCS) regression were used to analyze the correlation between the TyG index and related TyG indicators and the incidence rate of cardiovascular disease. To compare predictive performance, time-dependent Harrell’s C-indices, net reclassification index and integrated discrimination improvement were conducted.ResultsResearch shows that the TyG index and all TyG-related indexes can predict the incidence rate of CVD. RCS regression analysis showed that all indicators were linearly related to the incidence rate of CVD. The linear relationship between TyG and waist circumference (TyG-WC) or waist-to-height ratio (TyG-WHtR) still exists in CKM stages 1, 2, and 3. Compared with the TyG index (C-index: 0.611, p<0.001) and TyG-BMI (C-coefficient: 0.616, p<0.001), TyG-WC (C-index: 0.621, p<0.001) and TyG-WHtR (C-index: 0.621, p<0.001) have better effects on predicting the incidence rate of CVD.ConclusionBoth the TyG index and the TyG-related index are independent predictors of the incidence rate of CVD in patients with CKM syndrome stage 0-3. Importantly, TyG-WC and TyG-WHtR have a better predictive effect.

Tiziana Ronti, Graziana Lupattelli, Elmo Mannarino

SummaryAdipose tissue secretes bioactive peptides, termed ‘adipokines’, which act locally and distally through autocrine, paracrine and endocrine effects. In obesity, increased production of most adipokines impacts on multiple functions such as appetite and energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism and haemostasis, all of which are linked with cardiovascular disease. Enhanced activity of the tumour necrosis factor and interleukin 6 are involved in the development of obesity‐related insulin resistance. Angiotensinogen has been implicated in hypertension and plasminogen activating inhibitor‐1 (PAI‐1) in impaired fibrinolysis. Other adipokines like adiponectin and leptin, at least in physiological concentrations, are insulin sparing as they stimulate beta oxidation of fatty acids in skeletal muscle. The role of resistin is less understood. It is implicated in insulin resistance in rats, but probably not in humans. Reducing adipose tissue mass, through weight loss in association with exercise, can lower TNF‐α and IL‐6 levels and increase adiponectin concentrations, whereas drugs such as thiazolinediones increase endogenous adiponectin production. In‐depth understanding of the pathophysiology and molecular actions of adipokines may, in the coming years, lead to effective therapeutic strategies designed to protect against atherosclerosis in obese patients

Xi May Zhen, Stephen M. Twigg, Ted Wu et al.

Abstract Background Diabetes presenting in young adults is often challenging to classify. Diabetic ketoacidosis is typically seen in autoimmune type 1 diabetes mellitus and more rarely in young onset type 2 diabetes mellitus. Beta-ketothiolase deficiency (BKD) is a rare autosomal recessive condition affecting isoleucine catabolism and ketone body metabolism. BKD typically manifests in childhood as recurrent episodes of ketoacidosis, the frequency of which tends to reduce with age. There is a paucity of data with respect to the co-existence of persistent dysglycemia with BKD. Case presentation and literature review We present a novel case of diabetes presenting as diabetic ketoacidosis in a 34-year-old man with BKD, with genetically confirmed compound heterozygosity for variants in ACAT1, including a novel ACAT1 c.481T>C, p.(Tyr161His) variant. Diabetes in people with BKD presents unique diagnostic and management challenges. To further contextualize our findings, we conducted a comprehensive narrative review of the existing literature with respect to dysglycemia in those with BKD, especially in adulthood. There are no existing reports describing diabetes in adults with BKD. Stress hyperglycemia is not uncommon when children with BKD are acutely unwell, with several pediatric case reports describing short-lived hyperglycemia but normal HbA1c measurements during metabolic crises (indicating the absence of persistent hyperglycemia). Conclusions This is the first report of diabetic ketoacidosis in an adult with BKD, with an elevated HbA1c consistent with persistent hyperglycemia. This case highlights the importance of checking HbA1c in people with BKD and hyperglycemia in order to uncover potential coexisting diabetes, facilitating timely management and preventing complications. Increased reporting on the longitudinal outcomes of those with rare metabolic disorders is essential for identifying potential associations with conditions like diabetes.

James Young, Juan Maria Ibarra Co

A 66-year old woman presented to us with syncope and carpopedal spasm. The history of her condition started 10 years ago as recurrent loss of consciousness associated with carpopedal spasm occurring at 2-3 times in a year. A medical consult led to a diagnosis of hypocalcemia, and she has since been maintained on oral calcium supplementation

Dong-Rong Yang, Dong-Rong Yang, Meng-Yan Wang et al.

Diabetic vascular complications are prevalent and severe among diabetic patients, profoundly affecting both their quality of life and long-term prospects. These complications can be classified into macrovascular and microvascular complications. Under the impact of risk factors such as elevated blood glucose, blood pressure, and cholesterol lipids, the vascular endothelium undergoes endothelial dysfunction, characterized by increased inflammation and oxidative stress, decreased NO biosynthesis, endothelial-mesenchymal transition, senescence, and even cell death. These processes will ultimately lead to macrovascular and microvascular diseases, with macrovascular diseases mainly characterized by atherosclerosis (AS) and microvascular diseases mainly characterized by thickening of the basement membrane. It further indicates a primary contributor to the elevated morbidity and mortality observed in individuals with diabetes. In this review, we will delve into the intricate mechanisms that drive endothelial dysfunction during diabetes progression and its associated vascular complications. Furthermore, we will outline various pharmacotherapies targeting diabetic endothelial dysfunction in the hope of accelerating effective therapeutic drug discovery for early control of diabetes and its vascular complications.

Simonetta Marucci, Luca Busetto, Marco Chianelli et al.

Binge eating disorder (BED) is the most common eating disorder categorized in the DSM-V, but it is often not diagnosed in patients with obesity because it can be difficult to detect in these patients who often have altered eating patterns. In this narrative review, we have highlighted the most recent findings in the screening, diagnosis, and treatment of patients with BED and obesity. The results of our search showed that many BED patients are not obese, and most people with obesity do not have binge behavior. In the diagnostic assessment of these patients, it is important to evaluate not only the clinical and nutritional status and the presence of medical comorbidities, but also the psychological signs and symptoms related to psychiatric comorbidities to define the appropriate diagnosis and the consequent level of treatment. Well-tolerated drugs with action on both body weight and binges can be useful as a second-line complement to cognitive behavioral therapy (CBT). Specific guidelines are needed to obtain consensus on appropriate recommendations in patients with obesity and BED approaching bariatric surgery, taking into account not only weight reduction and clinical data, but also eating behaviors. Identification of BED is important for targeting individuals at high risk of obesity, adverse metabolic patterns, and cardiovascular disease. The challenge is to also achieve lasting weight loss in patients with BED and concomitant obesity.

Jennifer M. Barker

Bella A. Azimova, Konstsantin Yu. Nikolayev, Anton S. Vorobyov et al.

The review presents modern studies the effect of genetic polymorphisms on the efficienty and safety of therapy with new oral anticoagulants. Hepatic carboxylesterase encoded by the CES1 gene and P-glycoprotein encoded by the ABCB1 gene affect dabigatran pharmacokinetics. The role of glucuronidation enzymes (UGT2B15, UGT1A9, UGT2B7) involved in active dabigatran metabolism is poorly understood. An increase in the peak apixaban concentration was noted in patients with the rs4148738 polymorphism of the ABCB1 gene. Polymorphisms rs776746 and rs77674 of the CYP3A5 gene affect concentration of apixaban in Asian patients and thus increased the bleeding risk. The effect SULT1A1 sulfotransferase on the metabolism of apixaban has yet to be studied. The BCRP protein encoded by the ABCG2 gene is a poorly studied but promising direction for the pharmacokinetics of apixaban. ABCB1 and CYP3A4 of the cytochrome P450 system affect the rivaroxaban metabolism, however, the number of studies devoted to examining the effect of polymorphisms of these genes on the rivaroxaban pharmacokinetics limited. Thus, large studies are needed to clarify the clinical relevance of genotyping in target patients taking new oral anticoagulants.

Yaqian Mao, Zheng Zhu, Shuyao Pan et al.

Abstract Aims/Introduction To compare the application value of different machine learning (ML) algorithms for diabetes risk prediction. Materials and Methods This is a 3‐year retrospective cohort study with a total of 3,687 participants being included in the data analysis. Modeling variable screening and predictive model building were carried out using logistic regression (LR) analysis and 10‐fold cross‐validation, respectively. In total, six different ML algorithms, including random forests, light gradient boosting machine, extreme gradient boosting, adaptive boosting (AdaBoost), multi‐layer perceptrons and gaussian naive bayes were used for model construction. Model performance was mainly evaluated by the area under the receiver operating characteristic curve. The best performing ML model was selected for comparison with the traditional LR model and visualized using Shapley additive explanations. Results A total of eight risk factors most associated with the development of diabetes were identified by univariate and multivariate LR analysis, and they were visualized in the form of a nomogram. Among the six different ML models, the random forests model had the best predictive performance. After 10‐fold cross‐validation, its optimal model has an area under the receiver operating characteristic value of 0.855 (95% confidence interval [CI] 0.823–0.886) in the training set and 0.835 (95% CI 0.779–0.892) in the test set. In the traditional LR model, its area under the receiver operating characteristic value is 0.840 (95% CI 0.814–0.866) in the training set and 0.834 (95% CI 0.785–0.884) in the test set. Conclusions In the real‐world epidemiological research, the combination of traditional variable screening and ML algorithm to construct a diabetes risk prediction model has satisfactory clinical application value.

Kaori Oda, Satoshi Miyamoto, Ryo Kodera et al.

Abstract Aims/Introduction Nucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasomes produce IL‐18 upon being activated by various stimuli via the P2 receptors. Previously, we showed that serum and urine IL‐18 levels are positively associated with albuminuria in patients with type 2 diabetes, indicating the involvement of inflammasome activation in the pathogenesis of diabetic kidney disease (DKD). In the present study, we investigated whether the administration of suramin, a nonselective antagonist of the P2 receptors, protects diabetic KK.Cg‐Ay/TaJcl (KK‐Ay) mice against DKD progression. Materials and Methods Suramin or saline was administered i.p. to KK‐Ay and C57BL/6J mice once every 2 weeks for a period of 8 weeks. Mouse mesangial cells (MMCs) were stimulated with ATP in the presence or absence of suramin. Results Suramin treatment significantly suppressed the increase in the urinary albumin‐to‐creatinine ratio, glomerular hypertrophy, mesangial matrix expansion, and glomerular fibrosis in KK‐Ay mice. Suramin also suppressed the upregulation of NLRP3 inflammasome‐related genes and proteins in the renal cortex of KK‐Ay mice. P2X4 and P2X7 receptors were significantly upregulated in the isolated glomeruli of KK‐Ay mice and mainly distributed in the glomerular mesangial cells of KK‐Ay mice. Although neither ATP nor suramin affected NLRP3 expression in MMCs, suramin inhibited ATP‐induced NLRP3 complex formation and the downstream expression of caspase‐1 and IL‐18 in MMCs. Conclusions These results suggest that the NLRP3 inflammasome is activated in a diabetic kidney and that inhibition of the NLRP3 inflammasome with suramin protects against the progression of early stage DKD.

Sathia González Guzmán, Araceli Alejandra Soto-Novia, Luisa Mariana Calvillo Centeno et al.

Background: Early enteral nutrition (EEN) has shown favorable clinical outcomes, such as lower risk of death, fewer frequency of infection and less healthcare costs. Different societies recommend the provision of enteral nutrition in the first 24 to 48 hours of admission to the Intensive Care Unit in patients with COVID-19. Methods: This was a retrospective cohort study in adult patients with severe COVID-19 and orotracheal intubation. Demographic and clinical characteristics and laboratory results were registered. Data was also collected on the use of drugs with nutritional relevance, such as vasopressors and steroids. EEN was defined as the provision of enteral feeding in the first 24-48 hours of invasive mechanical ventilation (IMV). Primary outcome was in-hospital all-cause mortality. Results: Four hundred four patients were included in the study. EEN was achieved in 74% of all patients. EEN significantly reduced the mortality in the bivariate model (RR 0.88, 95% CI 0.80 a 0.95) and in the multivariate model (adjusted OR 0.42, 95% CI 0.19 – 0.90). No differences in hospital length of stay and days on IMV in survivors were found. Conclusions: EEN reduces the risk of death in critically ill patients with COVID-19. Additional studies are necessary to further clarify the effects of early enteral feeding in patient outcomes.

Congfu Huang, Haiying Liu, Wei Yang et al.

Precocious puberty (PP) is one of the most common endocrine diseases in children, and the pathogenesis is currently unknown. Recent studies on the gut-brain axis have shown that there is a correlation between childhood endocrine diseases and the gut microbiota (GM). To explore the GM characteristics of children with different types of PP, we recruited 27 idiopathic central precocious puberty children (ICPP group), 18 peripheral precocious puberty children (PPP group), and 23 healthy children of the same age (HC group). Their stool samples were subjected to 16S rDNA sequencing. In this study, we found that the OTUs numbers, the annotated genera, and α-diversity of GM of the ICPP and PPP group were all significantly higher than that in the HC group (P<0.05). The abundance of butyrate-producing bacteria Prevotella, Lachnospiracea incertae sedis, Roseburia, Ruminococcus, and Alistipes was significantly higher in the ICPP group and the PPP group, and Bacteroides and Faecalibacterium showed significantly higher abundance in the HC group. The GM symbiosis network showed that both Bacteroides and Faecalibacterium were negatively correlated with these butyrate-producing bacteria. The abundances of most significantly changed genera were gradually increased from HC to PPP, and to the ICPP group, while only Bacteroides was gradually decreased. After the prediction of the metabolic pathways of the GM, the cell motility, signal transduction, and environmental adaptation were significantly enriched in the ICPP and the PPP groups (P<0.05), while the carbohydrate metabolism pathway was significantly lower (P<0.001). Overall, this study showed that the GM composition and predicted functional pattern of children with ICPP and PPP are different from healthy children, and PPP may be a transitional stage between ICPP and HC children, which provide a theoretical basis for clinical intervention based on GM in the treatment of PP.

M.N Joshi, B.C. Whitelaw, M.T.P. Palomar et al.

SummaryImmune checkpoint inhibitors are a new and effective class of cancer therapy, with ipilimumab being the most established drug in this category. The drugs’ mechanism of action includes promoting the effector T cell response to tumours and therefore increased autoimmunity is a predictable side effect. The endocrine effects of these drugs include hypophysitis and thyroid dysfunction, with rare reports of adrenalitis. The overall incidence of hypophysitis with these medications is up to 9%. Primary thyroid dysfunction occurs in up to 15% of patients, with adrenalitis reported in approximately 1%. The mean onset of endocrine side effects is 9 weeks after initiation (range 5–36 weeks). Investigation and/or screening for hypophysitis requires biochemical and radiological assessment. Hypopituitarism is treated with replacement doses of deficient hormones. Since the endocrine effects of immune checkpoint inhibitors are classed as toxic adverse events, most authors recommend both discontinuation of the immune checkpoint inhibiting medication and ‘high‐dose’ glucocorticoid treatment. However, this has been challenged by some authors, particularly if the endocrine effects can be managed (e.g. pituitary hormone deficiency), and the therapy is proving effective as an anticancer agent. This review describes the mechanism of action of immune checkpoint inhibitors and details the key clinical endocrine‐related consequences of this novel class of immunotherapies.

Sabo, Roy, Robins, Jo, Lutz, Stacy et al.

BackgroundPatients with type 2 diabetes require recommendations for self-management education and support. ObjectiveIn this study, we aim to design the Diabetes Engagement and Activation Platform (DEAP)—an automated patient education tool integrated into primary care workflow—and examine its implementation and effectiveness. MethodsWe invited patients aged 18-85 years with a hemoglobin A1c (HbA1c) level ≥8 to participate in a randomized controlled trial comparing DEAP with usual care. DEAP modules addressing type 2 diabetes self-management education and support domains were programmed into patient portals, each with self-guided educational readings, videos, and questions. Care teams received patient summaries and were alerted to patients with low confidence or requesting additional help. HbA1c, BMI, and systolic and diastolic blood pressure (DBP) were measured. ResultsOut of the 680 patients invited to participate, 337 (49.5%) agreed and were randomized. All of the 189 intervention patients accessed the first module, and 140 patients (74.1%) accessed all 9 modules. Postmodule knowledge and confidence scores were high. Only 18 patients requested additional help from the care team. BMI was lower for intervention patients than controls at 3 months (31.7 kg/m2 vs 32.1 kg/m2; P=.04) and 6 months (32.5 kg/m2 vs 33.0 kg/m2; P=.003); improvements were even greater for intervention patients completing at least one module. There were no differences in 3- or 6-month HbA1c or blood pressure levels in the intent-to-treat analysis. However, intervention patients completing at least one module compared with controls had a better HbA1c level (7.6% vs 8.2%; P=.03) and DBP (72.3 mm Hg vs 75.9 mm Hg; P=.01) at 3 months. ConclusionsThe findings of this study concluded that a significant proportion of patients will participate in an automated virtual diabetes self-management program embedded into patient portals and health systems show promise in helping patients manage their diabetes, weight, and blood pressure. Trial RegistrationClinicalTrials.gov NCT02957721; https://clinicaltrials.gov/ct2/show/NCT02957721

Daria Di Filippo, Thiyasha Wanniarachchi, Daniel Wei et al.

Abstract Background Gestational diabetes mellitus (GDM) is glucose intolerance first recognised during pregnancy. Both modalities and thresholds of the GDM diagnostic test, the Oral Glucose Tolerance Test (OGTT), have varied widely over time and among countries. Additionally, OGTT limitations include inconsistency, poor patient tolerability, and questionable diagnostic reliability. Many biological parameters have been reported to be modified by GDM and could potentially be used as diagnostic indicators. This study aimed to 1) systematically explore biomarkers reported in the literature as differentiating GDM from healthy pregnancies 2) screen those indicators assessed against OGTT to propose OGTT alternatives. Main body A systematic review of GDM diagnostic indicators was performed according to PRISMA guidelines (PROSPERO registration CRD42020145499). Inclusion criteria were full-text, comprehensible English-language articles published January 2009-January 2021, where a biomarker (from blood, ultrasound, amniotic fluid, placenta) was compared between GDM and normal glucose tolerance (NGT) women from the second trimester onward to immediately postpartum. GDM diagnostic method had to be clearly specified, and the number of patients per study higher than 30 in total or 15 per group. Results were synthesised by biomarkers. Results Of 13,133 studies identified in initial screening, 174 studies (135,801 participants) were included. One hundred and twenty-nine studies described blood analytes, one amniotic fluid analytes, 27 ultrasound features, 17 post-natal features. Among the biomarkers evaluated in exploratory studies, Adiponectin, AFABP, Betatrophin, CRP, Cystatin-C, Delta-Neutrophil Index, GGT, TNF-A were those demonstrating statistically and clinically significant differences in substantial cohorts of patients (> 500). Regarding biomarkers assessed versus OGTT (i.e. potential OGTT alternatives) most promising were Leptin > 48.5 ng/ml, Ficolin3/adiponectin ratio ≥ 1.06, Chemerin/FABP > 0.71, and Ultrasound Gestational Diabetes Score > 4. These all demonstrated sensitivity and specificity > 80% in adequate sample sizes (> / = 100). Conclusions Numerous biomarkers may differentiate GDM from normoglycaemic pregnancy. Given the limitations of the OGTT and the lack of a gold standard for GDM diagnosis, advanced phase studies are needed to triangulate the most promising biomarkers. Further studies are also recommended to assess the sensitivity and specificity of promising biomarkers not yet assessed against OGTT. Trial registration PROSPERO registration number CRD42020145499.

Manoranjan Tripathy, A K Baliarsinha, A K Choudhury et al.

Background: Various hormonal parameters used to differentiate between different causes of pubertal disorders are invasive, cumbersome, and has variable sensitivity and specificity. Thus, the use of a noninvasive test like urinary gonadotropin for the diagnosis of pubertal disorders will offer a significant advantage. Objective: To study the role of urinary gonadotropins (uLH, uFSH) for the diagnosis of various pubertal disorders and in the monitoring of Gonadotrophin releasing hormone, Hypothalamic-pituitary-gonadal (GnRHa) therapy in patients with central precocious puberty (CPP). Materials and Methods: We evaluated 35 healthy children and 96 patients with disorders of puberty out of which 31 cases had early puberty and 65 cases had delayed puberty. We used Spearman's correlation coefficient to evaluate the correlation between the serum and urinary gonadotropins. We used Mann–Whitney U test (for 2 groups) and Kruskal–Wallis test (for > 2 groups) to compare the median urinary and serum gonadotropins of different groups. Results: The urinary gonadotropins correlated strongly with serum gonadotropins in both healthy controls and individuals with pubertal disorders. The uLH level of ≥0.76 IU/L had 100% sensitivity and specificity to differentiate CPP from peripheral precocious puberty, whereas uLH level of ≥1.07 IU/L had 100% sensitivity and specificity for differentiating CPP from PT. In patients with delayed puberty, uFSH of ≥20.51 IU/L had 94.7% sensitivity and 91.3% specificity for the diagnosis of Hyper-Hypo cases and uLH level of ≥0.5 IU/L had sensitivity of 96.2% and specificity of 85% to differentiate constitutional delay in growth and puberty from hypogonadotropic-hypogonadism. In CPP patients on GnRHa therapy, the uLH level of ≥0.13 IU/L had 100% sensitivity and 86.7% specificity to identify those who had nonsuppressed serum LH levels. Conclusion: The urinary gonadotropins can be used as a reliable noninvasive test for the diagnosis of various pubertal disorders and also for monitoring of CPP patients on GnRHa therapy.

Hyung Eun Shin, Jeremy D. Walston, Jeremy D. Walston et al.

ObjectiveThe association of free testosterone (FT) with sarcopenia and its components is well known in men but incompletely understood in women. We examined the association of baseline FT with the prevalence and incidence of sarcopenia and its components in community-dwelling older adults.DesignCross-sectional and longitudinal analysis from the prospective population-based Korean Frailty and Aging Cohort Study.MethodsA total of 1,879 community-dwelling older adults aged 70–84 years were enrolled for cross-sectional analysis and 1,583 subjects who participated in the 2-year follow-up survey were included for longitudinal analysis. Baseline FT levels was measured by radioimmunoassay. Skeletal muscle mass, handgrip strength, and physical performance tests were measured at baseline and after 2-year follow-up. Sarcopenia was defined by the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS).ResultsContinuous FT levels was positively associated with the prevalence of sarcopenia in men (odds ratio [OR]=0.95; 95% confidence interval [CI]=0.89–1.00)] and women (OR=0.64, 95% CI=0.42–0.99) after adjusting for multiple confounders. In prospective analysis, low FT levels was associated with a decrease in handgrip strength in women (β=-0.61; p=0.010) and a reduction in Timed “Up and Go” (TUG) test (β=0.53; p=0.008) in men after 2 years. No significant correlations were found between FT levels and the incidence of sarcopenia.ConclusionsLow levels of FT may be a significant determinant of decreases in muscle strength in women and declines in physical performance in men after 2 years. Low FT do not predict loss of muscle mass in both men and women.

Ning Wang, Bo Sun, Haonan Guo et al.

ObjectiveTo study the discrepancy of the insulin sensitivity alteration pattern, circulating fibroblast growth factor (FGF21) levels and FGF21 signaling in visceral white adipose tissue (vWAT) of gestational diabetes mellitus (GDM) subtypes.Methods26 GDM women with either a predominant of insulin-secretion defect (GDM-dysfunction, n = 9) or insulin-sensitivity defect (GDM-resistance, n = 17) and 13 normal glucose tolerance (NGT) women scheduled for caesarean-section at term were studied. Blood and vWAT samples were collected at delivery.ResultsThe insulin sensitivity was improved from the 2nd trimester to delivery in the GDM-resistance group. Elevated circulating FGF21 concentration at delivery, increased FGF receptor 1c and decreased klotho beta gene expression, enhanced ERK1/2 phosphorylation, and increased GLUT1, IR-B, PPAR-γ gene expression in vWAT were found in the GDM-resistance group as compared with the NGT group. The circulating FGF21 concentration was negatively correlated with fasting blood glucose (r = -0.574, P &lt; 0.001), and associated with the GDM-resistance group (r = 0.574, P &lt; 0.001) in pregnant women at delivery. However, we observed no insulin sensitivity alteration in GDM-dysfunction and NGT groups during pregnancy. No differences of plasma FGF21 level and FGF21 signaling in vWAT at delivery were found between women in the GDM-dysfunction and the NGT group.ConclusionsWomen with GDM heterogeneity exhibited different insulin sensitivity alteration patterns. The improvement of insulin sensitivity may relate to the elevated circulating FGF21 concentration and activated FGF21 signaling in vWAT at delivery in the GDM-resistance group.

Adipose tissue plays a central role in regulating whole-body energy. Moreover, adipose tissue acts as an endocrine organ and produces numerous bioactive factors called adipokines which communicate with other organs and modulate a range of metabolic pathways: proteins (adiponectin, angiopoietins, chemerin, etc.), lipids (fatty acid esters of hydroxyl fatty acids, lysophosphatidic acids and sphingolipids), metabolites (uric acid and uridine) and microRNAs. However, excessive adipose tissue is associated with a chronic state of low-grade inflammation, caused by unbalanced production or secretion of these adipokines and can contribute to the development of obesity [1].