Successful Diagnoses and Remarkable Metabolic Disorders in Patients With Solitary Hypothalamic Mass: A Case Series Report.

Background: Solitary intracranial hypothalamic mass occurs rarely. The etiological diagnosis of solitary hypothalamus lesion is challenging and often unachievable. Although previous studies indicated that lesions affecting the hypothalamus often cause significant metabolic disorders, few reports about the metabolic disturbances of patients with solitary hypothalamic mass have been reported. Method: Twenty-five patients with solitary hypothalamus lesions who had been evaluated and treated in Huashan Hospital from January 2010 to December 2020 were retrospectively enrolled. The clinical manifestations, radiological features, endocrine and metabolic disorders, and pathology were analyzed. Results: The male to female ratio was 5/20. The median age of onset was 22 (19, 35) years old. The most common initial symptom was polydipsia/polyuria (19/25, 76.0%) and amenorrhea (9/20, 45.0%). A high prevalence of hypopituitarism of different axes was found, with almost all no less than 80%. Central hypogonadism (21/22, 95.5%) and central diabetes insipidus (19/21, 90.5%) were the top two pituitary dysfunctions. Conclusive diagnoses were achieved by intracranial surgical biopsy/resection or stereotactic biopsy in 16 cases and by examining extracranial lesions in 3 cases. The pathological results were various, and the most common diagnoses were Langerhans cell histiocytosis (7/19) and hypothalamitis (5/19). The mean timespan from onset to diagnosis in the 19 cases was 34 ± 26 months. Metabolic evaluations revealed remarkable metabolic disorders, including hyperlipidemia (13/16, 81.3%), hyperglycemia (10/16, 62.5%), hyperuricemia (12/20, 60%), overweight/obesity (13/20, 65.0%), and hepatic adipose infiltration (10/13, 76.6%). Conclusion: Either surgical or stereotactic biopsy will be a reliable and relatively safe procedure to help to confirm the pathological diagnosis of solitary hypothalamic mass. Metabolic disorders were severe in patients with solitary hypothalamic mass. The management of such cases should cover both the treatment of the primary disease, as well as the endocrine and metabolic disorders.

Transition from metabolically healthy to unhealth status associated with risk of carotid artery plaque in Chinese adults.

OBJECTIVE: We aimed to evaluate the association between the shift of metabolic status and future risk of carotid artery plaque (CAP) in community-based Chinese adults. METHODS: The current study included 9836 Chinese adults (4085 males and 5751 females, mean age 35.8 years) with metabolically healthy status at baseline (2013). Metabolically healthy status was defined as no self-reported history of metabolic diseases and cancer, and normal blood pressure, fasting blood glucose, glycated hemoglobin A1c level, and lipid profiles. Metabolically unhealthy status was defined if any of the following metabolic abnormalities were confirmed twice during follow up: high blood pressure, impaired glucose regulation, high triglycerides, high total cholesterol, high low-density lipoprotein cholesterols, or low high-density lipoprotein cholesterols. The transition was confirmed if participants' metabolic status shifted from baseline healthy to unhealthy status during follow up (2014-2018). RESULTS: We have identified 133 incident cases of CAP during follow up. Compared to those who remained metabolically healthy, the transition to high blood pressure, high total cholesterol, and high low-density lipoprotein cholesterols, were associated with high risk of developing carotid artery plaque (Hazards ratios (HRs) ranged from 1.69 to 2.34; p < 0.05 for all). The transition to impaired glucose regulation, high total triglycerides, and low high-density lipoprotein cholesterols, were associated with high risk of carotid artery plaque only in participants with metabolically healthy overweight at baseline (HR ranged from 1.95 to 4.62; p < 0.05 for all). CONCLUSION: The transition from baseline metabolically healthy status to unhealth status was associated with high risk of incident CAP.

Association of Diet, Physical Activity Guidelines and Cardiometabolic Risk Markers in Children.

The aim was to identify different dietary and physical activity (PA) patterns in 5- to 14-year-old children with a high prevalence of overweight and obesity using cluster analysis based on their adherence to the Spanish Society of Community Nutrition dietary guidelines and levels of PA, and to determine their associations with age, sex, body composition, and cardiometabolic risk markers. In 549 children, hierarchical cluster analysis was used to identify subgroups with similar adherence to dietary recommendations and level of PA. Three clusters were identified: Cluster 1, with the lowest level of vigorous PA and adherence to dietary recommendations; Cluster 2, with the lowest levels of moderate and vigorous PA and the highest adherence to dietary recommendations; and Cluster 3, with the highest level of PA, especially vigorous PA and a medium level adherence to dietary recommendations. Cluster 3 had lower total body fat and higher lean body mass percentages than Cluster 2. Cluster 2 had lower high-density lipoprotein cholesterol and higher low-density lipoprotein cholesterol levels than Cluster 1. The results from our study suggest that it is important to consider adherence to PA recommendations together with adherence to dietary guidelines to understand patterns of obesogenic habits in pediatric populations with high prevalence of overweight and obesity.

Plasma Free Fatty Acid Concentration as a Modifiable Risk Factor for Metabolic Disease.

Plasma free fatty acid (FFA) concentration is elevated in obesity, insulin resistance (IR), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and related comorbidities such as cardiovascular disease (CVD). Furthermore, experimentally manipulating plasma FFA in the laboratory setting modulates metabolic markers of these disease processes. In this article, evidence is presented indicating that plasma FFA is a disease risk factor. Elevations of plasma FFA can promote ectopic lipid deposition, IR, as well as vascular and cardiac dysfunction. Typically, elevated plasma FFA results from accelerated adipose tissue lipolysis, caused by a high adipose tissue mass, adrenal hormones, or other physiological stressors. Reducing an individual's postabsorptive and postprandial plasma FFA concentration is expected to improve health. Lifestyle change could provide a significant opportunity for plasma FFA reduction. Various factors can impact plasma FFA concentration, such as chronic restriction of dietary energy intake and weight loss, as well as exercise, sleep quality and quantity, and cigarette smoking. In this review, consideration is given to multiple factors which lead to plasma FFA elevation and subsequent disruption of metabolic health. From considering a variety of medical conditions and lifestyle factors, it becomes clear that plasma FFA concentration is a modifiable risk factor for metabolic disease.

Extra cellular vesicles in blood circulation as biomarkers and messengers of patho-hysiological activity and alterations.

There is an increasing interest in Extracellular Vesicles released by many cells through membrane shedding. In addition to cell signaling, these particles are true messenger cargos, which can carry cell surface proteins, miRNAs and non-coding RNAs to other and distant cells. They are part of the inter-cellular crosstalk and they contribute to transferring biological messages far away from the triggering event. EVs are biomarkers of many diseases, including thrombo-embolic pathology, infections, neurological or metabolic disorders, and malignancy. Their role and significance are presented and discussed in this short review, as consequences of disease and causes of its progression. But they can also be beneficial for tissue healing or repair, and they can be prepared in vitro to be used for cell- targeted treatments. Many identification and measurement methods for EV's are sophisticated, which restricts their use to research studies, but they have, nevertheless, a high laboratory potential for diagnosis, prognosis and evolution as follow-up of many pathologies. New emerging laboratory tools offer more friendly and easy applications for characterizing EVs and testing their associated activity, especially for the procoagulant ones.

Untargeted metabolomics analysis by gas chromatography/time-of-flight mass spectrometry of human serum from methamphetamine abusers.

Methamphetamine (METH) abuse has become a global public health problem. However, the potential mechanisms involving METH-induced metabolic disorders have thus far remained poorly understood. Metabolomics can provide a clue for the cause of apparent changes and consequently be used to investigate the METH-induced dysregulation of metabolite expression and the mechanism of metabolic disorder mechanism. This laboratory investigation included 80 METH abusers and 80 healthy people. The serum metabolites were detected and analysed by gas chromatography/time-of-flight mass spectrometry. Raw data were processed with the software MS DIAL, which includes deconvolution, peak alignment and compound identification. The data matrix was processed by univariate and multivariate analyses for significant metabolite screening with the criteria of variable importance in projection values > 1, fold change > 1.5 and the t test (p value < 0.05). Significant differences in 16 metabolites (deoxycholic acid, cholic acid, hydroxylamine, etc.) in serum were found between the METH abuse group and the control group. Energy metabolic pathways and several amino acid metabolic pathways (alanine, aspartic acid and glutamate metabolism and tryptophan metabolism) were primarily involved. Further analysis indicated that the area under the receiver operating characteristic curve (AUC) was 0.998 for these 16 metabolites. Among the metabolites, three carbohydrates (d-ribose, cellobiose and maltotriose) had an AUC of 0.975, which were determined as potential markers of abuse. We observed metabolic disturbances in METH abusers, particularly perturbation in energy metabolism and amino acid metabolism, which can provide new insights into the search for biomarkers and the mechanisms underlying the adverse effects of METH on human health.

Circulating bacterial signature is linked to metabolic disease and shifts with metabolic alleviation after bariatric surgery.

BACKGROUND: The microbiome has emerged as an environmental factor contributing to obesity and type 2 diabetes (T2D). Increasing evidence suggests links between circulating bacterial components (i.e., bacterial DNA), cardiometabolic disease, and blunted response to metabolic interventions. In this aspect, thorough next-generation sequencing-based and contaminant-aware approaches are lacking. To address this, we tested whether bacterial DNA could be amplified in the blood of subjects with obesity and high metabolic risk under strict experimental and analytical control and whether a putative bacterial signature is related to metabolic improvement after bariatric surgery. METHODS: Subjects undergoing bariatric surgery were recruited into sex- and BMI-matched subgroups with (n = 24) or without T2D (n = 24). Bacterial DNA in the blood was quantified and prokaryotic 16S rRNA gene amplicons were sequenced. A contaminant-aware approach was applied to derive a compositional microbial signature from bacterial sequences in all subjects at baseline and at 3 and 12 months after surgery. We modeled associations between bacterial load and composition with host metabolic and anthropometric markers. We further tested whether compositional shifts were related to weight loss response and T2D remission. Lastly, bacteria were visualized in blood samples using catalyzed reporter deposition (CARD)-fluorescence in situ hybridization (FISH). RESULTS: The contaminant-aware blood bacterial signature was associated with metabolic health. Based on bacterial phyla and genera detected in the blood samples, a metabolic syndrome classification index score was derived and shown to robustly classify subjects along their actual clinical group. T2D was characterized by decreased bacterial richness and loss of genera associated with improved metabolic health. Weight loss and metabolic improvement following bariatric surgery were associated with an early and stable increase of these genera in parallel with improvements in key cardiometabolic risk parameters. CARD-FISH allowed the detection of living bacteria in blood samples in obesity. CONCLUSIONS: We show that the circulating bacterial signature reflects metabolic disease and its improvement after bariatric surgery. Our work provides contaminant-aware evidence for the presence of living bacteria in the blood and suggests a putative crosstalk between components of the blood and metabolism in metabolic health regulation.

SHBG as a Marker of NAFLD and Metabolic Impairments in Women Referred for Oligomenorrhea and/or Hirsutism and in Women With Sexual Dysfunction.

PCOS is one of the most common endocrine disorders and NAFLD is one of its most dangerous metabolic consequences. The diagnosis of NAFLD is not a practical task and the condition is at risk of being overlooked. The use of simpler but still reliable surrogate markers is necessary to identify women with a high likelihood of NAFLD. The aim of this study was to evaluate the clinical correlates of NAFLD Liver Fat Score (NAFLD-LFS) in women with oligomenorrhea and/or hirsutism. Furthermore, the study aimed to evaluate whether, among the hormonal parameters evaluated in such women, possible hallmarks of NAFLD may be identified. To this purpose, 66 women who attended our Outpatient Clinic for oligomenorrhea and/or hyperandrogenism were included in the study. In order to validate the results obtained in the first cohort, a second independent sample of 233 women evaluated for female sexual dysfunction (FSD) was analyzed. In cohort 1, NAFLD-LFS positively correlated with metabolic and inflammatory parameters. Among the hormone parameters, NAFLD-LFS showed no significant relationships with androgens but a significant negative correlation with SHBG (p<0.0001) that therefore appeared as a candidate hallmark for pathologic NAFLD-LFS. The ROC analysis showed a significant accuracy (81.1%, C.I.69.1-93.0, p <0.0001) for SHBG in identifying women with a pathological NAFLD-LFS. In particular, a SHBG 33.4 nmol/l was recognized as the best threshold, with a sensitivity of 73.3% and a specificity of 70.7%. In order to validate this SHBG as a marker of metabolic impairment possible related with the presence of NAFLD, we tested this threshold in cohort 2. FSD women with SHBG <33.4 nmol/l had worse metabolic parameters than women with SHBG ≥33.4 nmol/l and a significantly higher NAFLD-LFS even after adjusting for confounders (B=4.18 [2.05; 6.31], p=0.001). In conclusion, this study provides a new evidence in the diagnostic process of NAFLD, showing that the measurement of SHBG, which is routinely assessed in the workup of women referred for possible PCOS, could identify women at higher metabolic risk, thus detecting those who may deserve further targeted diagnostic assessment.

Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?

RATIONALE AND OBJECTIVE: Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. METHODS: We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. RESULTS: Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-ß levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients' BMI, blood glucose, and proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1ß and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. CONCLUSION: Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.

Factors Influencing Total Serum IgE in Adults: The Role of Obesity and Related Metabolic Disorders.

BACKGROUND AND AIM: Few reports have investigated the association between metabolic abnormalities (obesity and related metabolic syndrome) and total serum IgE concentrations. METHODS: This cross-sectional study included a random sample of 1,516 adult individuals (44.7% men, aged 18-91 years, median 52 years) from a single municipality in Spain. Serum IgE was measured in the ADVIA Centaur system. Atopy was defined by the presence of positive skin prick tests to a panel of common aeroallergens in the area. Body mass index and data related to the definition of metabolic syndrome were obtained from all participants. Alcohol consumption, smoking, and regular physical exercise were assessed by a questionnaire. RESULTS: Atopy (present in 21.9% of 1,514 evaluable individuals) was the strongest factor determining serum IgE concentrations. Male sex and heavy alcohol drinking were independently associated with higher IgE concentrations, particularly in the non-atopic individuals. Body mass index was positively associated with IgE concentrations, independent of potential confounders, although the effect was only evident among non-atopic individuals. In that group, median IgE concentrations in normal-weight and obese individuals were 15 and 24 kU/L, respectively (p < 0.001); likewise, obesity was associated with high (>100 kU/L) IgE concentrations after adjusting for potential confounders (odds ratio: 1.79, 95% confidence interval: 1.26-2.56, p = 0.001). The presence of metabolic syndrome and its components, particularly abdominal obesity and hyperglycaemia, was also positively and independently associated with higher IgE concentrations in non-atopic individuals. CONCLUSIONS: Obesity and metabolic syndrome components are associated with high total serum IgE concentrations, particularly in non-atopic individuals.

Comparison of metabolic and obesity biomarkers between adolescent and adult women with polycystic ovary syndrome.

PURPOSE: Knowledge of adolescent and adult phenotypes of women with polycystic ovary syndrome (PCOS) might drive opportune management. The aim of this study was to compare metabolic and obesity biomarkers between adolescent and adult women with PCOS. METHODS: This observational study compared biomarkers of obesity and metabolism derangements between adolescent (n = 62) and adult (n = 248) women with PCOS. Predictors of metabolic syndrome (MS) were investigated using univariate and multivariate binary logistic regression analysis. RESULTS: The postmenarcheal age of adolescents was 4.9 ± 0.03 years. Systolic blood pressure was lower in adolescents than in adults (112.3 mmHg vs 117.0 mmHg, p = 0.001) Diastolic blood pressure was also lower in adolescents (70.7 mmHg vs 75.8 mmHg, p < 0.001). Glucose intolerance (12.0% vs 19.3%) and insulin resistance (18.2% vs 17.7%) were similar in both groups (p > 0.05, for comparisons). Impaired fasting glucose was lower in adolescents (1.8% vs 11.6%, p = 0.015). Total cholesterol and low-density lipoprotein cholesterol were lower in adolescents (p < 0.001). MS in adolescents and adults were found in 10.3% and 27.8%, respectively (p = 0.005). Visceral adiposity index (VAI) was a good predictor of MS in both adolescents (OR = 12.2), and adults (OR = 9.7). CONCLUSIONS: Most biomarkers of glucose metabolism abnormalities were similar in adolescents and adults with PCOS. The prevalence of MS was lower in adolescents. VAI was a strong predictor of metabolic syndrome, both in adolescent and adult women with PCOS.

Non-classical effects of vitamin D: Non-bone effects of vitamin D.

Our understanding of vitamin D has improved considerably in recent years. The role of vitamin D in preventing osteoporotic fractures is now well-established. However, an important controversy has emerged in the last decade concerning the effects of the active form of vitamin D (1,25-dihydroxy-vitamin D) on tissues other than bone (non-classical effects). The demonstration that the vitamin D receptor (VDR) is ubiquitously, expressed combined with increasing observational data supporting a relationship between the level of 25-hydroxy-vitamin D in the serum and chronic metabolic disorders, cardiovascular disease and neoplasms, have led to its redefinition as a steroid hormone and the proposal of its use in preventing and/or treating those diseases. This article is an update on the different non-bone or non-classical effects of "vitamin-hormone D", and its potential preventive or therapeutic role in certain diseases, however, this review is not exhaustive. The different modalities of substitution or supplementation proposed in France by the Groupe de Recherche et d'Information sur les Ostéoporoses (GRIO) are also summarised.

Granzyme B Expression in Visceral Adipose Tissue Associates With Local Inflammation and Glyco-Metabolic Alterations in Obesity.

Granzyme B (GrB) is a serine protease produced by immune and non-immune cells, able to promote multiple processes, like apoptosis, inflammation, extracellular matrix remodeling and fibrosis. GrB expression in visceral adipose tissue (VAT) was associated with tissue damage, local inflammation and insulin resistance in obesity murine model, but there is no data in humans. Aim of this study was to explore the expression of GrB in VAT from obese subjects in relation to adipose tissue injury, inflammation, metabolic alterations and GrB circulating levels. For this purpose, 85 obese individuals undergoing bariatric surgery and 35 healthy subjects (as control) were recruited at Sapienza University, Rome, Italy. Study participants underwent clinical work-up and routine biochemistry. mRNA expression of GrB in VAT and of a panel of VAT inflammatory markers was analyzed by real-time PCR. Serum GrB levels were measured by Elisa Affymetrix EBIO. We observed that 80% of obese patients expressed GrB mRNA in VAT, and GrB VAT expression was associated with the presence of local inflammation and glucose homeostasis alterations. Moreover, GrB serum levels, which were higher in obese subjects compared to non-obese healthy individuals, were associated with GrB expression in VAT and glyco-metabolic impairment. Our data show, for the first time in humans, that obese subjects with "sick" fat and altered glucose tolerance exhibit GrB expression in VAT, and suggest that GrB might contribute to obesity-related VAT inflammatory remodeling and glucose homeostasis dysregulation. Moreover, increased circulating GrB levels might represent a possible peripheral marker of VAT dysfunction in metabolic diseases.

The influences of DNA methylation and epigenetic clocks, on metabolic disease, in middle-aged Koreans.

BACKGROUND: Considering that DNA methylation (DNAm) profiles are, in large part, modifiable by lifestyle and environmental influences, it has been proposed that epigenetic clocks provide a better estimate of biological age than chronological age, as associated with current health status. Even though metabolic diseases induce precocious aging, little is known about associations between metabolic syndrome (MetS) and DNA methylation clocks, and stochastic epigenetic mutations (SEMs), in a Korean population. Therefore, we assessed four different epigenetic clocks (Pan-tissue, Hannum, PhenoAge, and GrimAge), and their accelerations, on MetS and MetS-related lifestyle factors, in Koreans. We measured genome-wide DNA methylation (485,512 CpGs), using an Illumina 450 methylation BeadChip array, with data from 349 blood samples. RESULTS: DNAm GrimAge strongly correlated with chronological age (r = 0.77, p < 0.001) compared to the other three epigenetic clocks and SEMs. DNAm-based surrogate markers, with regard to MetS, including the gene encoding plasminogen activator inhibitor-1 (PAI1), also correlated with chronological age. Within cohorts stratified by age group, sex, regional area, smoking, and alcohol drinking, a positive correlation was observed between DNAm GrimAge and chronological age (0.43 ≤ r ≤ 0.78). In particular, we identified MetS to associate with accelerated GrimAge, and age-adjusted PAI1, in the middle-age group. Accerelated GrimAge also associated with risk of MetS in the middle-age group (odds ratio = 1.16, p = 0.046), which appears to mediate their associations with fasting glucose. Multiple linear regression showed that DNAm GrimAge, and its acceleration, associate with MetS scores, in the middle-age group (r = 0.26, p = 0.006). Age-adjusted PAI1 was also significantly different between the MetS and control groups, and further associated with MetS scores (r = 0.31, P < 0.001), in the middle age group. CONCLUSION: DNAm GrimAge is a surrogate marker for MetS, and its component score, in Koreans. This association can be observed only in middle age. Therefore, appropriate DNA methylation clocks may aid in the prediction of Korean metabolic diseases.

Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD).

BACKGROUND: Although metabolic associate fatty liver disease (MAFLD) is associated with obesity, it can also occur in lean patients. MAFLD is more aggressive in lean patients compared to obese patients, with a higher risk of mortality. Specific biomarkers to diagnose differentially lean or overweight MAFLD are missing. Histones and nucleosomes are released in the bloodstream upon cell death. Here, we propose a new, fast, imaging and epigenetics based approach to investigate the severity of steatosis in lean MAFLD patients. RESULTS: A total of 53 non-obese patients with histologically confirmed diagnosis of MAFLD were recruited. Twenty patients displayed steatosis grade 1 (0-33%), 24 patients with steatosis grade 2 (34-66%) and 9 patients with steatosis grade 3 (67-100%). The levels of circulating nucleosomes were assayed using enzyme-linked immunosorbent assay, while individual histones or histone dimers were assayed in serum samples by means of a new advanced flow cytometry ImageStream(X)-adapted method. Circulating nucleosome levels associated poorly with MAFLD in the absence of obesity. We implemented successfully a multi-channel flow methodology on ImageStream(X), to image single histone staining (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2). We report here a significant depletion of the levels of histone variants macroH2A1.1 and macroH2A1.2 in the serum of lean MAFLD patients, either individually or in complex with H2B. CONCLUSIONS: In summary, we identified a new circulating histone signature able to discriminate the severity of steatosis in individuals with lean MAFLD, using a rapid and non-invasive ImageStream(X)-based imaging technology.

Association between serum magnesium and anemia in patients with chronic kidney disease.

PURPOSE: An inverse association was shown between serum magnesium levels and anemia in the general population. However, limited information is available about the association between serum magnesium level and anemia in the patient population with chronic kidney disease. We aimed to investigate the relationship between hypomagnesemia and anemia in pre-dialysis patients with chronic kidney disease stage 3-5. METHODS: This cross-sectional retrospective study included 213 chronic kidney disease patients with an estimated glomerular filtration rate of 60 mL/min and below. Laboratory and demographic data of outpatients were collected in January 2018-January 2019. Patients with a magnesium level below 1.9 mg/dL were accepted as the hypomagnesemia group. RESULTS: Serum magnesium level of 62 (29.1%) of these patients were below 1.9 mg/dL. Compared with normomagnesemic patients, hypomagnesemic patients had lower mean hemoglobin values (11.3 g/dL vs. 12.7 g/dL, P < 0.001), proton-pump inhibitor usage rates were significantly higher (33.9% vs. 17.2%, P = 0.008) and the median urine protein/creatinine ratio was found to be significantly higher (1017.5 mg/gCr vs. 536 mg/gCr, P = 0.045). In the multivariate analysis, the use of hemoglobin (OR 0.634; 95% CI 0.505-0.795; P < 0.001) and proton-pump inhibitor (OR 2.670; 95% CI 1.113-6.318; P = 0.025) were independent predictors of hypomagnesemia. CONCLUSIONS: Hypomagnesemia is a common electrolyte disorder in pre-dialysis CKD patients. In this patient group, anemia is independently associated with hypomagnesemia.

The impact of high-intensity interval training on inflammatory markers in metabolic disorders: A meta-analysis.

INTRODUCTION: High-intensity interval training (HIIT) is considered a time-efficient strategy to improve metabolic health. We performed a systematic meta-analysis to assess the effects of HIIT on inflammatory markers and adipo-cytokines compared with control conditions (CON) or moderate-intensity continuous training (MICT) in individuals with metabolic disorders. METHODS: Up to January 2020, electronic databases were searched for HIIT interventions based on populations with metabolic disorders including diabetes, metabolic syndrome, polycystic ovary syndrome, non-alcoholic fatty liver disease or overweight/obesity, with outcome measurements that included IL-6, TNF-α, CRP, leptin or adiponectin and training ≥2 weeks. Random-effects models were used to aggregate a mean effect size (ES), 95% confidence intervals (Cis), and potential moderators were explored. RESULTS: Twenty-nine studies involving 841 participants were included in the meta-analysis. HIIT improved circulating adiponectin (P = .02), leptin (P = .02), and TNF-α (P = .003) when compared to CON. There were no differences between groups in IL-6 and CRP. Intervention duration was a significant moderator for the effect of HIIT on IL-6, and leptin (P < .05). CONCLUSION: High-intensity interval training improves circulating TNF-α, leptin and adiponectin, thereby indicating that it may be an effective and time-efficient intervention for controlling low-grade inflammation in individuals with metabolic disorders.

The Association Between Prolactin and Metabolic Parameters in PCOS Women: A Retrospective Analysis.

Background: The aim of this retrospective study was to analyze the association between prolactin (PRL) and metabolic parameters in infertile patients with polycystic ovary syndrome (PCOS). Methods: A total of 2,052 patients with PCOS and 9,696 patients with tubal infertility (non-PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET) at the reproductive medicine center of the first affiliated hospital of Wenzhou Medical University from January 2007 to July 2017 were enrolled in this study. Serum PRL, basic endocrine hormones, fasting plasma lipid, fasting plasma glucose (FPG), liver function, thyroid hormone and other parameters were measured and analyzed. Result: PRL levels were significantly lower in PCOS patients than controls over all age groups (p < 0.05). In the PCOS patients, serum PRL was significantly and positively correlated with FPG, serum TSH and serum FT4, and significantly and negatively correlated with LH, LH/FSH, TC, TG, LDL-C, AST, ALT, γ-GGT, FT3, and FT3/FT4 (p < 0.05 or 0.01). After adjusted for age and body mass index (BMI), serum PRL was positively correlated with FPG, TSH, and FT4, and negatively correlated with LH and LH/FSH. Conclusion: Low serum PRL may be an important cause of metabolic risk in infertile patients with PCOS.

Sex Differences in Long-term Metabolic Effects of Maternal Resveratrol Intake in Adult Rat Offspring.

Maternal nutrition can affect the susceptibility of the offspring to metabolic disease later in life, suggesting that this period is a window of opportunity for intervention to reduce the risk of metabolic disease. Resveratrol, a natural polyphenol, has a wide range of beneficial properties including anti-obesogenic, anti-atherosclerotic, and anti-diabetic effects. We previously reported that maternal resveratrol intake during pregnancy and lactation has early metabolic effects in the offspring with these effects at weaning depending on the type of diet ingested by the mother and the offspring's sex. Here we analyzed whether these metabolic changes are maintained in the adult offspring and if they remain sex and maternal diet dependent. Wistar rats received a low-fat diet (LFD; 10.2% Kcal from fat) or high fat diet (HFD; 61.6% Kcal from fat) during pregnancy and lactation. Half of each group received resveratrol in their drinking water (50 mg/L). Offspring were weaned onto standard chow on postnatal day 21. Maternal resveratrol reduced serum cholesterol levels in all adult offspring from HFD mothers and increased it in adult female offspring from LFD mothers. Resveratrol increased visceral adipose tissue (VAT) in LFD offspring in both sexes but decreased it in male HFD offspring. Resveratrol shifted the distribution of VAT adipocyte size to a significantly higher incidence of large adipocytes, regardless of sex or maternal diet. These results clearly demonstrate that maternal resveratrol intake has long-lasting effects on metabolic health of offspring in a sex specific manner with these effects being highly dependent on the maternal diet.

Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83-2.76, p < 0.001, I2 99%). T2DM data were from 12 studies, with 22.8 million individuals followed up for a median of 10 years (IQR 6.4 to 16.9) experiencing 72,792 liver events. Fourteen studies were included in the meta-analysis of obesity (BMI > 30 kg/m2) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12-1.28, p < 0.001, I2 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta-analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome. CONCLUSIONS: In this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease. TRIAL REGISTRATION: PROSPERO CRD42018115459.