Biomarkers Of Glucose Metabolism Research Articles

Cognitive performance in young adult women with a history of premature adrenarche.

Girls with premature adrenarche (PA) mature earlier than peers and have been found to have greater symptom accounts reflecting anxiety compared to peers. It is not known, however, whether PA effects cognitive development. This longitudinal case-control cohort study aimed: (1) To investigate whether a history of PA leads to measurable changes in adulthood cognitive performance, and (2) to assess whether findings characteristic of PA girls predict adulthood cognitive performance. Twenty-seven girls with PA and 27 age-matched control girls were examined and followed from mid-childhood (mean age 7.2 years) until early adult age (18.5 years). Wechsler Adult Intelligence Scale, Fourth Edition scores were used as main outcome measure. Allostatic load (AL) scores, which compile multisystem variables to reflect the overall wear and tear of the body from increased and prolonged stress, were higher in the PA group in both prepuberty and adulthood, but there were no differences in WAIS-IV results between the groups (full-scale IQ 92.7 vs. 97.5, p 0.376; no differences in separate indexes). Childhood androgen levels, glucose metabolism biomarkers, and AL scores failed to predict adulthood cognitive performance outcomes. The study suggests that PA does not predispose to adverse adulthood outcomes of cognitive development. The study suggests that a history of premature adrenarche (PA) does not affect cognitive performance in adult age. Childhood androgen levels and biomarkers of glucose metabolism failed to predict adulthood cognitive outcomes in this study. Allostatic load scores were elevated in the PA group both in childhood and adulthood but did not predict adulthood cognitive outcomes.

Association of Age at Menarche with Inflammation and Glucose Metabolism Biomarkers in U.S. Adult Women: NHANES 1999-2018.

Early age at menarche (AAM) is a risk factor for type 2 diabetes later in life, but the pathogenic pathways that confer increased risk remain unknown. We examined the associations between AAM and inflammatory and glucose metabolism biomarkers among U.S. adult women who were free of diabetes. Using the National Health and Nutrition Examination Survey (NHANES) 1999-2018, 19,228 women over 20 years old who were free of self-reported cancer and diabetes were included in this cross-sectional analysis. AAM was the self-reported age at first menstruation. CRP, fasting glucose, fasting insulin, and ferritin levels were measured as biomarkers of inflammation and glucose metabolism in adult blood samples using latex-enhanced nephelometry, enzymatic, and immunoassay methods. Multiple linear regression was used to relate AAM to the biomarkers. The median age at the time of blood sample collection was 44 years (IQR, 33-62). After age adjustment, there was an association between a lower AAM and higher CRP (P-trend=0.006); fasting glucose (P-trend<0.0001); fasting insulin (P-trend <0.0001); and ferritin (p-trend<0.0001). These remained significant after additional adjustment for demographic, reproductive, lifestyle, and adiposity variables, except for ferritin. Smoking modified the effect of AAM on CRP (p-interaction = 0.014), fasting insulin (p-interaction <0.001), and fasting glucose (p-interaction<0.001). In stratified analysis, the observed associations became more pronounced in non-smokers, while they were attenuated to non-significance in active smokers. Earlier age at menarche is associated with an unfavorable inflammatory and glucose metabolic biomarker profile in a nationally representative sample of adult women free of diabetes, especially among non-smokers.

The association between the Canadian active living environments index and glucose metabolism in a Canadian national population study

Biomarkers of glucose metabolism may reflect insulin resistance, a risk factor for diabetes and cardiovascular disease (CVD). Neighborhoods conducive to a physically active lifestyle have the potential to improve these biomarkers. We examined cross-sectional associations between walkability and blood biomarkers of glucose metabolism in 29,649 Canadian Health Measures Survey (CHMS) participants. We used generalized linear mixed models with sampling weights adjusted for province, participants’ age, sex, annual household income and educational attainment, cigarette smoking, environmental tobacco smoke, alcohol consumption, and exposure to ambient fine particulate air pollution (PM2.5). A higher value of the Canadian Active Living Environments Index, a measure of neighborhood walkability, equivalent to the magnitude of its interquartile range (IQR) of 2.4 was significantly associated with percentage differences of −0.48 (95% confidence interval (CI): 0.63, −0.32), −3.17 (95%CI: 5.27, −1.08), −3.88 (95%CI: 6.38, −1.38), and −3.36 (95%CI: 5.25, −1.47) in HbA1C, fasting insulin, HOMA-IR, and HOMA-β, respectively, for all CHMS participants. No significant effects were observed in those ≤16 years old. Canadians living in neighborhoods that facilitate active living have more favorable biomarkers of glucose metabolism, suggesting that the built environment has the potential to improve risk factors for diabetes and CVD in adults.

Exploring the In Vitro Protective Effects of Green-Lipped Mussel (GLM) Oil Extract against Biomarkers of Glucose Metabolism and Inflammation in Chondrocyte Cells

Chondrocyte behavior is critical in osteoarthritis (OA) progression and cartilage deterioration. Recent studies have shown that green-lipped mussel (GLM) oil extracts obtained through solvent extraction can regulate cytokine secretion in cell lines, potentially reducing inflammation and immune cell activation. This study investigates the effects of these extracts on human chondrocyte cell lines to understand their impact on osteoarthritis development. Chondrocyte cultures exposed to osteoarthritis-related inflammatory factors were treated with various concentrations of GLM oil. The results revealed that mussel oils, particularly a commercial mussel powder extract (SOLV.COM), enhance glucose uptake and protect chondrocyte cells. SOLV.COM effectively manages the release of inflammatory markers like interleukin-6 (IL-6) and matrix metalloproteinases-3 (MMP-3), showing increased deoxyglucose uptake. This study highlights the significant influence of extract choice on managing interleukin-6 (IL-6) secretion and cellular activation pathways, demonstrating the potential of SOLV.COM in managing osteoarthritis by controlling reactive oxygen production, regulating glucose metabolism, and inflammatory markers.

Effects of biological agents on glycogen metabolism in psoriasis patients: A systematic review and meta-analysis.

The effectiveness and safety of biological agents for treating psoriasis have been confirmed; however, their effects on glucose metabolism biomarkers in psoriasis patients remain unclear. A systematic review and meta-analysis were performed according to PRISMA guidelines. The final analysis enrolled 12 studies, including eight randomized controlled trial (RCT) (n = 5628 patients) and four observational cohort studies (OBSs) (n = 393 patients). The meta-analysis comprising nine studies (six RCTs and three OBSs) revealed a slight reduction in the levels of HOMA-IR associated with the use of biological therapies in OBS (biological therapies vs. traditional therapies: WMD = -0.2, CI = -0.10 to 0.50, p = 0.02). Although a considerable number of studies were analysed, our review did not show a significant alteration in HOMA-IR levels among patients treated with biological therapies such as IL-17 inhibitors and IL-12/23 inhibitors at weeks 12-16 in RCTs. We also did not observe remarkable alterations in the fasting plasma glucose levels of patients in both OBS and RCT. Additional RCT on a larger scale and duration is required to provide more conclusive evidence regarding the effect of biological agents on glycogen metabolism in psoriasis.

Physical Activity and Cardiovascular Risk Factors in Children from 4 to 9 Years of Age

BackgroundPhysical activity guidelines for children encourage moderate-to-vigorous intensity activities (MVPA); however, some studies have found that only vigorous intensity activities (VPA) might promote health benefits in young children. Thus, the aim of this study is to investigate cross-sectional and 5-year longitudinal associations of VPA and MVPA with cardiovascular disease (CVD) risk factors in childhood using compositional data analysis.ResultsThis study utilized data from the SPINACH study (n = 411). Physical activity was measured with accelerometers at 4- and 9-years of age. CVD risk factors were measured at 9-years of age, and included blood pressure (BP), lipid metabolism, and glucose metabolism biomarkers, as well as a continuous metabolic syndrome risk score (MetS). Cross-sectional and longitudinal linear regression models were built using compositional data analysis standards. Cross-sectionally, reallocating time to VPA from lower-intensity behaviours at 9-years was associated with lower waist circumference (B = − 3.219, P = 0.002), diastolic BP (B = − 1.836, P = 0.036), triglycerides (B = − 0.214, P < 0.001), glucose (B = − 0.189, P = 0.033), insulin (B = − 2.997, P < 0.001), and HOMA-IR (B = − 0.778, P < 0.001). Similarly, reallocating time to VPA at 4-years was associated with lower MetS (B = − 0.831, P = 0.049), waist circumference (B = − 4.211, P = 0.015), systolic BP (B = − 5.572, P = 0.015), diastolic BP (B = − 2.931, P = 0.044), triglycerides (B = − 0.229, P = 0.034), glucose (B = − 0.325, P = 0.032), insulin (B = − 5.114, P = 0.001), and HOMA-IR (B = − 0.673, P = 0.001) at 9-years. Reallocations of time to MVPA at 4- or 9-years were not associated with CVD risk factors at 9-years.ConclusionsVPA was associated with CVD risk factors in children both cross-sectionally (9-years) and longitudinally (at 4- and 9-years). MVPA seemed not to be a stimulus of enough intensity to trigger these potential cardiometabolic benefits in healthy children. Thus, these findings suggest the importance of higher intensity activities, i.e., VPA already in early childhood for cardiometabolic health.

Influence of general anaesthesia on circulating biomarkers of glucose metabolism in pigs.

Pigs are widely used in metabolic research with procedures often requiring general anaesthesia. The aim was to investigate the effect of four different anaesthetic protocols: 1) isoflurane inhalation, 2) propofol infusion, 3) a mixture of tiletamine, zolazepam, medetomidine, ketamine and butorphanol (TZMKB)) and 4) ketamine combined with midazolam and xylazine (KMX)) on selected biomarkers during basal and glucose stimulated conditions. Eight domestic pigs were included in a cross-over design. Plasma concentrations of glucose, insulin, C-peptide, glucagon, cortisol, triglycerides, total cholesterol, aspartate amino transferase and alanine amino transferase, creatinine, urea, fructosamine, albumin, free fatty acids (FFAs) and glycerol were measured at baseline, during 2 h of anaesthesia and during 1 h of recovery. Intravenous glucose tolerance test (IVGTT, 0.5 g glucose/kg) was performed after 1 h of anaesthesia. Glucose disappearance rate and areas under the insulin, C-peptide and glucagon curves from the IVGTT were calculated. All four anaesthetic protocols affected glucose metabolism parameters significantly compared with un-anaesthetised pigs, which was particularly evident during IVGTT and for TZMKB and KMX anaesthesia. Propofol additionally influenced the plasma concentrations of triglycerides, FFAs and glycerol significantly. The remaining circulating biomarkers were largely unaffected by anaesthesia. These data underline the importance of considering the anaesthetic protocol in porcine studies of circulating metabolic biomarkers.

Glucose metabolism, hippocampal subfields and cognition in first-episode and never-treated schizophrenia

BackgroundPrevious studies have indicated that glucose metabolism and altered hippocampal structure and function play a pivotal role in cognitive deficits in schizophrenia (SZ). This study was designed to explore the inter-relationship between glucose metabolism, hippocampal subfield volume, and cognitive function in the antipsychotics-naive first episode (ANFE) SZ patients. MethodsWe chose the fasting insulin, glucose, and insulin resistance (HOMA-IR) index as biomarkers of glucose metabolism. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). The hippocampal subfield volume, glucose metabolism biomarkers, and cognitive function were evaluated in 43 ANFE SZ and 29 healthy controls (HCs). ResultsCompared with HCs, SZ patients had higher fasting blood glucose and insulin levels and HOMA-IR (all p < 0.05). Correlation analysis revealed that category fluency performance was positively associated with fasting glucose level. Fasting insulin or HOMA-IR was positively associated with the hippocampal subfield volume in patients (all p<0.05). Moreover, the spatial span index score was associated with the volume of the right presubiculum, subiculum, and right hippocampal tail. In addition, multiple regression analysis found that the interaction effects of insulin × right fimbria or insulin × left fimbria were independent predictors of the MCCB total score. ConclusionsOur findings suggest that abnormal glucose metabolism and cognitive decline occur in the early stage of SZ. The interaction between abnormal glucose metabolism and hippocampal subfields was associated with cognitive functions in SZ.

Dietary Supplements Containing Oat Beta-Glucan and/or Green Coffee (Poly)phenols Showed Limited Effect in Modulating Cardiometabolic Risk Biomarkers in Overweight/Obese Patients without a Lifestyle Intervention.

Obesity has reached pandemic proportions and has become a major health concern worldwide. Therefore, it is necessary to find new strategies against this condition and its associated comorbidities. Green coffee polyphenols (GCP) and oat beta-glucans (BGs) have proven their hypolipidaemic and hypoglycaemic effects. This study aimed to examine the effects of the long-term consumption of supplements containing GCP, BG or the novel GCP/BG combination on lipid and glucose metabolism biomarkers in overweight/obese subjects who maintained their dietary habits and physical activity, hence addressing the difficulty that this population faces in adapting to lifestyle changes. A randomised, crossover, blind trial was carried out in 29 volunteers who consumed either GCP (300 mg), BG (2.5 g) or GCP/BG (300 mg + 2.5 g) twice a day for 8 weeks. Blood samples were collected, and blood pressure and body composition were measured at the beginning and end of each intervention. Total cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), very low-density lipoprotein (VLDL-C) cholesterol, glycated haemoglobin, fasting glucose, insulin, aspartate transaminase, alanine transaminase and different hormones and adipokines were analysed. Only VLDL-C (p = 0.01) and diastolic blood pressure (p = 0.027) decreased after the intervention, especially with the BG supplement. There were no other significant changes in the analysed biomarkers. In conclusion, the regular intake of GCP, BG and GCP/BG without lifestyle changes is not an efficient strategy to improve lipid and glucose homeostasis in overweight/obese subjects.

Overview of the Study on the Effect of Sucralose on Blood Glucose

For this purpose, we collected the clinical studies evaluating the effect of sucralose intake on blood glucose since 1996; the properties and metabolic characteristics of sucralose, the changes in blood glucose levels, and related biomarkers of glucose metabolism in different populations after single and long-term intake of sucralose were also summarized and reviewed.

Habitual coffee consumption and subsequent risk of type 2 diabetes in individuals with a history of gestational diabetes – a prospective study

Females with a history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes mellitus (T2D) later in life. This study prospectively examined whether greater habitual coffee consumption was related to a lower risk of T2D among females with a history of GDM. We followed 4522 participants with a history of GDM in the NHS II for incident T2D between 1991 and 2017. Demographic, lifestyle factors including diet, and disease outcomes were updated every 2-4 y. Participants reported consumption of caffeinated and decaffeinated coffee on validated FFQs. Fasting blood samples were collected in 2012-2014 from a subset of participants free of diabetes to measure glucose metabolism biomarkers (HbA1c, insulin, C-peptide; n=518). We used multivariable Cox regression models to calculate adjusted HRs and 95% CIs for the risk of T2D. We estimated the least squares mean of glucose metabolic biomarkers according to coffee consumption. A total of 979 participants developed T2D. Caffeinated coffee consumption was inversely associated with the risk of T2D. Adjusted HR (95% CI) for≤1 (nonzero), 2-3, and 4+cups/d compared with 0 cup/d (reference) was 0.91 (0.78, 1.06), 0.83 (0.69, 1.01), and 0.46 (0.28, 0.76), respectively (P-trend=0.004). Replacement of 1 serving/d of sugar-sweetened beverage and artificially sweetened beverage with 1 cup/d of caffeinated coffee was associated with a 17% (risk ratio [RR]=0.83, 95% CI: 0.75, 0.93) and 9% (RR=0.91, 95% CI: 0.84, 0.99) lower risk of T2D, respectively. Greater caffeinated coffee consumption was associated with lower fasting insulin and C-peptide concentrations (all P-trend<0.05). Decaffeinated coffee intake was not significantly related to T2D but was inversely associated with C-peptide concentrations (P-trend=0.003). Among predominantly Caucasian females with a history of GDM, greater consumption of caffeinated coffee was associated with a lower risk of T2D and a more favorable metabolic profile.

Association of smartphone-recorded steps over years and change in cardiovascular risk factors among working aged adults

Abstract Backgrounds Evidence indicates a causal role of physical activity (PA), including steps, in decreasing cardiovascular disease (CVD) risk. However, few data exist on long-term steps and their relation to changes in CVD risk factors. Objectives To examine the associations of long-term smartphone-recorded steps and changes in CVD-related biomarkers in a large cohort of working aged adults. Methods The present analysis made use of data two national database and a commercial app database. Participants who underwent an annual health check-up between April 2015 and November 2020 and a second health check-up 24 to 35 months thereafter, and whose daily step data were available, were included. We evaluated the associations between smartphone-recorded daily steps over two years following the initial health check-up and two-year changes in the following CVD risk factors: weight, waist, blood pressure (BP), lipid and glucose metabolism biomarkers. Generalized additive models were used to investigate the non-linear relationships of steps and changes in CVD risks. Models were adjusted for baseline steps and other confounders. The present study design is summarized in Figure 1. Results A total of 15,708 participants with mean (SD) age of 44.1 (9.5) and 23.5% women were included. Differences in weight were almost linearly associated with two-year steps in men (estimate [SE] per 1000 steps/day: −0.33 [0.029] kg), and inversely related only above 5,000 steps/day in women (−0.18 [0.054] kg) (Figure 2). Similar trends were observed in waist. An inverse linear association with systolic BP was observed in men (−0.34 [0.097] mmHg) but not in women. Greater steps were associated with favorable change in HDL cholesterol and triglycerides (0.61 [0.068] and −3.4 [0.61] mg/dL in men; 0.64 [0.17] and −2.3 [0.67] mg/dL in women), while negative changes in LDL cholesterol was evident in men only (−0.59 [0.17] mg/dL). A significant negative association with HbA1c was observed only in women (−0.012 [0.0043] %). In the secondary analyses of the associations between one-year steps and one-year (i.e., 12 to 23 months) changes in CVD related biomarkers (N=26,884), the relationships were weaker and less robust compared with those in two-year analyses. Conclusions In a large cohort of Japanese adults, smartphone-recorded steps over years were associated with beneficial changes in CVD risk factors, with some differences between men and women in the associational patterns. The sex differences might highlight the undercount of steps among women who may be less likely to always carry their phone [1], or true sex differences in the effects of steps. The findings support the benefit of long-term PA for CVD health and suggest a useful role of smartphone-recorded steps for monitoring CVD risk over the long term. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): DeSC Healthcare Inc., Tokyo, Japan

The Effect of a Comprehensive Life-Style Intervention Program of Diet and Exercise on Four Bone-Derived Proteins, FGF-23, Osteopontin, NGAL and Sclerostin, in Overweight or Obese Children and Adolescents.

The adipose and bone tissues demonstrate considerable interconnected endocrine function. In the present study, we determined the concentrations of fibroblast growth factor-23 (FGF-23), osteopontin, neutrophil gelatinase-associated lipocalin (NGAL) and sclerostin in 345 children and adolescents who were overweight or obese (mean age ± SD mean: 10.36 ± 0.16 years; 172 males, 173 females; 181 prepubertal; and 164 pubertal) before and after their participation in a comprehensive life-style intervention program of diet and exercise for one year. Following the one-year life-style interventions, there was a significant decrease in BMI (p < 0.01), FGF-23 (p < 0.05), osteopontin (p < 0.01) and NGAL (p < 0.01), and an increase in sclerostin (p < 0.01) concentrations. BMI z-score (b = 0.242, p < 0.05) and fat mass (b = 0.431, p < 0.05) were the best positive predictors and waist-to-height ratio (WHtR) (b = −0.344, p < 0.05) was the best negative predictor of the change of osteopontin. NGAL concentrations correlated positively with HbA1C (b = 0.326, p < 0.05), WHtR (b = 0.439, p < 0.05) and HOMA-IR (b = 0.401, p < 0.05), while BMI (b = 0.264, p < 0.05), fat mass (b = 1.207, p < 0.05), HDL (b = 0.359, p < 0.05) and waist circumference (b = 0.263, p < 0.05) were the best positive predictors of NGAL. These results indicate that FGF-23, osteopontin, NGAL and sclerostin are associated with being overweight or obese and are altered in relation to alterations in BMI. They also indicate a crosstalk between adipose tissue and bone tissue and may play a role as potential biomarkers of glucose metabolism. Further studies are required to delineate the physiological mechanisms underlying this association in children and adolescents.

Whole body vibration remodels skeletal muscle via autophagy and energy metabolism in diabetic mice.

Hyperglycemia occurs due to a defect in insulin secretion or impaired biological functions, or both. The long-term hyperglycemia during diabetes causes chronic damage and dysfunction of various tissues. Whole body vibration (WBV) has significant effects on lipid and glucose metabolism and endocrine and motor systems. In order to explore the effects of WBV on skeletal muscle, mice trained for 12 weeks with WBV (15 Hz, 30 min) were used as experimental subjects and their skeletal muscle morphology under the pathological state of diabetes was observed. In addition, the blood lipids, blood glucose, gastrocnemius muscle glycogen and mRNA and protein levels of autophagy and glucose metabolism biomarkers were compared among the three groups of mice via western blot and RT-qPCR. The results showed that WBV can significantly reshape skeletal muscle morphology and upregulate high density lipoprotein. The expression of glucose-6-phosphatase (G6P), Beclin1 and Atg7 in the gastrocnemius muscle of the WBV group was significantly increased. Therefore, it can be concluded that WBV promotes skeletal muscle remodeling in diabetic mice. The present study confirmed that WBV can attenuate the development of diabetes melitus (DM) and lead to lower level low density lipoprotein in the blood. In addition, G6P level plays an important role in WBV-treated DM model and may be used to monitor the effect of WBV in patients. The findings of the present study may provide a new molecular basis for WBV to play a therapeutic role in the treatment of diabetes and may have potential clinical applications in the future.

Higher Levels of Stress-Related Hair Steroid Hormones Are Associated with the Increased SCORE2 Risk Prediction Algorithm in Apparently Healthy Women.

Cardiovascular diseases (CVDs) are the major cause of death worldwide. Although the importance of conventional CVD risk factors, including older age, male gender, hypertension, obesity, dyslipidemia and hyperglycemia, is well-studied, psychosocial stress, which is considered an independent CVD risk factor, requires further investigation. Thus, we aimed to investigate the association between long-term secretion of stress-related steroid hormones, including cortisol, cortisone and dehydroepiandrosterone, and the 10-year fatal and non-fatal CVD risk estimated by the SCORE2 risk prediction algorithm, as well as traditional CVD risk factors in a group of apparently healthy women. A total of 145 women (aged 50–64 years) participating in the national CVD prevention program were enrolled in the study. Sociodemographic, lifestyle, health-related characteristics, stress, anxiety and sleep quality indicators were evaluated using specific questionnaires. Anthropometric and arterial blood pressure measures were assessed by trained personnel, lipid and glucose metabolism biomarkers were measured using routine methods, and hair steroid hormone levels were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. The results showed that higher levels of hair cortisol and cortisone are associated with increased SCORE2 values. Moreover, significant associations between hair glucocorticoids and individual cardiovascular risk factors, including obesity, hypertension, dyslipidemia and hyperglycemia, were found. These findings indicate that stress-related hair steroid hormones might be valuable biomarkers for CVD prediction and prevention.

Association between hepatic iron overload assessed by magnetic resonance imaging and glucose intolerance states in the general population

Background and aimWhile there is evidence that iron overload disorders are associated with type 2 diabetes, the relationship between hepatic iron overload and prediabetes remains unclear. We aimed to investigate the association between hepatic iron overload, as assessed by magnetic resonance imaging (MRI), and different glucose intolerance states in the population-based Study. Methods and resultsWe included data from 1622 individuals with MRI data, who did not have known type 2 diabetes (T2DM). Using an oral glucose tolerance testing, participants were classified as having isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT) or previously unknown T2DM. Hepatic iron and fat contents were assessed through quantitative MRI. We undertook linear and multinomial logistic regression models adjusted for potential confounders and MRI-assessed hepatic fat content to examine the association of hepatic iron overload with different glucose intolerance states or continuous markers of glucose metabolism.MRI-assessed hepatic iron overload was positively associated only with both 2-h plasma glucose (β = 0.32; 95%CI 0.04–0.60) and the combined IFG + IGT category (relative risk ratio = 1.87; 95%CI 1.15–3.06). No significant associations were found between hepatic iron overload and other glucose intolerance states or biomarkers of glucose metabolism, independently of potential confounders. ConclusionsMRI-assessed hepatic iron overload was associated with higher 2-h glucose concentrations and the combined IFG + IGT category, but not with other glucose intolerance states. Our findings suggest a weak adverse impact of hepatic iron overload on glucose metabolism, but further studies are needed to confirm these findings.

Biomaterial-mediated presentation of wnt5a mimetic ligands enhances chondrogenesis and metabolism of stem cells by activating non-canonical Wnt signaling

The presentation of development-relevant bioactive cues by biomaterial scaffolds is essential to the guided differentiation of seeded human mesenchymal stem cells (hMSCs) and subsequent tissue regeneration. Wnt5a is a critical non-canonical Wnt signaling ligand and plays a key role in the development of musculoskeletal tissues including cartilage. Herein we investigate the efficacy of biofunctionalizing the hyaluronic acid hydrogel with a synthetic Wnt5a mimetic ligand (Foxy5 peptide) to promote the chondrogenesis of hMSCs and the potential underlying molecular mechanism. Our findings show that the conjugation of Foxy5 peptide in the hydrogels activates non-canonical Wnt signaling of encapsulated hMSCs via the upregulation expression of PLCE1, CaMKII-β, and downstream NFATc1, leading to enhanced expression of chondrogenic markers such as SOX9. The decoration of Foxy5 peptide also promotes the metabolic activities of encapsulated hMSCs as evidenced by upregulated gene expression of mitochondrial complex components and glucose metabolism biomarkers, leading to enhanced ATP biosynthesis. Furthermore, the conjugation of Foxy5 peptide activates the non-canonical Wnt, PI3K-PDK-AKT and IKK/NF-κB signaling pathways, thereby inhibiting the hypertrophy of the chondrogenically induced hMSCs in the hydrogels under both in vitro and in vivo conditions. This enhanced chondrogenesis and attenuated hypertrophy of hMSCs by the biomaterial-mediated bioactive cue presentation facilitates the potential clinical translation of hMSCs for cartilage regeneration. Our work provides valuable guidance to the rational design of bio-inductive scaffolds for various applications in regenerative medicine.

A Systems-Level Analysis of Total-Body PET Data Reveals Complex Skeletal Metabolism Networks in vivo.

Bone is now regarded to be a key regulator of a number of metabolic processes, in addition to the regulation of mineral metabolism. However, our understanding of complex bone metabolic interactions at a systems level remains rudimentary. in vitro molecular biology and bioinformatics approaches have frequently been used to understand the mechanistic changes underlying disease at the cell level, however, these approaches lack the capability to interrogate dynamic multi-bone metabolic interactions in vivo. Here we present a novel and integrative approach to understand complex bone metabolic interactions in vivo using total-body positron emission tomography (PET) network analysis of murine 18F-FDG scans, as a biomarker of glucose metabolism in bones. In this report we show that different bones within the skeleton have a unique glucose metabolism and form a complex metabolic network, which could not be identified using single tissue simplistic PET standard uptake values analysis. The application of our approach could reveal new physiological and pathological tissue interactions beyond skeletal metabolism, due to PET radiotracers diversity and the advent of clinical total-body PET systems.

Effects of increased physical activity and/or weight loss diet on serum myokine and adipokine levels in overweight adults with impaired glucose metabolism.

The purpose of this study was to investigate the changes in serum irisin, fibroblast growth factor-21 (FGF21), visfatin, follistatin like protein-1 (FSTL1), and meteorin-like protein (Metrnl) levels in response to increased physical activity and/or diet interventions in overweight subjects with impaired glucose metabolism (IGM). A total of 60 subjects (BMI > 25.0 kg/m2) with IGM were recruited in this single-centered interventional study. Twelve subjects dropped out during the study and the study was completed with 48 patients. Patients were divided into two groups as diet only (DI, n = 24) and diet and physical activity intervention (DPA, n = 24). Patients in DI group received a diet program while DPA group received a diet combined with a physical activity intervention for 12 weeks. Additional 24 healthy subjects were recruited to compare the baseline levels of proteins. Serum protein levels, anthropometric measurements, and biochemical parameters were assessed. Irisin, FGF21, visfatin, and FSTL1 levels significantly decreased in both groups after 12-week intervention (p < 0.001). However, there were no differences in protein levels between DI and DPA groups (p > 0.05). Likewise, the total change in weight was similar in both DI (-4.35 kg) and DPA (-4.85 kg) groups (p > 0.05). A 5% reduction in initial body weight with DPA therapy resulted in a stronger correlation between the changes in irisin, visfatin, and FSTL1 levels and fasting glucose and HbA1c levels. These results demonstrate that serum irisin, FGF21, visfatin, and FSTL1 levels decreased in response to weight loss interventions. Weight loss induced by DI or DPA therapies had similar lowering effects on these proteins in subjects with IGM, and these myokines might be related to glucose metabolism biomarkers.

Characterization of a highly effective preparation for suppression of myocardial glucose utilization

BackgroundWith appropriate protocols, F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) can visualize myocardial inflammation. Optimal protocols and normative myocardial FDG uptake values are not well-established. MethodsWe evaluated 111 patients referred for inflammation cardiac FDG PET/CT. Patients followed a low-carbohydrate, high-fat diet for 36 hours before imaging and received unfractionated heparin. Glucose and fatty acid metabolism biomarkers were obtained. Mean blood pool and maximum myocardial uptake (SUVmean, SUVmax) were measured, avoiding areas of abnormal FDG uptake or spillover. ResultsAdequate suppression of myocardial FDG uptake occurred in 95% of patients (n = 106). Myocardial SUVmax was significantly below background blood pool SUVmean: septal myocardial to blood pool ratio 0.75 (95% CI 0.73-0.77; P < 0.001); lateral myocardial to blood pool ratio 0.70 (95% CI 0.68-0.72; P < 0.001). Glucose, insulin, and C-peptide correlated to blood pool SUVmean (Spearman rs = 0.39, P < 0.01; rs = 0.40, P < 0.01; rs = 0.35, P < 0.01) and myocardial SUVmax (Spearman rs = 0.31, P < 0.01; rs = 0.31, P < 0.01; rs = 0.26, P < 0.01). Fatty acid metabolism biomarkers did not correlate to myocardial SUVmax. ConclusionsPatients following intensive metabolic preparation have myocardial FDG SUVmax below background SUVmean. Biomarkers of glucose metabolism modestly correlate to FDG uptake.