Glycoprotein Acetylation Research Articles

Associations of coagulation parameters and thrombin generation potential with the incidence of type 2 diabetes: mediating role of glycoprotein acetylation.

Hypercoagulability is characterized by abnormal elevations of coagulation factor levels and increased thrombin generation potential. Prior studies demonstrated links between impaired glucose metabolism, endothelial dysfunction, and hypercoagulability. However, the associations between hypercoagulability and incident type 2 diabetes as well as its underlying mechanism remain unclear. We aimed to assess the associations between coagulation parameters including coagulation factor (F) VIII, FIX, FXI, fibrinogen, thrombin generation potential (lag time, endogenous thrombin potential [ETP], peak, time-to-peak, velocity) and incident type 2 diabetes, and to study the underlying mechanism by examining the mediating role of glycoprotein acetylation (GlycA). In the Netherlands Epidemiology of Obesity study, we applied a Cox Proportional-Hazards Model in 5718 participants after adjustment for confounders. We further conducted a mediation analysis investigating the mediation effect of GlycA on the observed associations. During a median follow-up of 6.7 years, 281 incident type 2 diabetes diagnoses were reported. Compared with the lowest quartile, hazard ratio (95% confidence interval) of the highest quartile was 2.47 (1.48-4.14) for FIX, 1.37 (0.85-2.20) for FVIII, 1.11 (0.76-1.63) for FXI, 0.98 (0.65-1.48) for fibrinogen, 1.56 (1.07-2.28) for ETP, 1.84 (1.23-2.74) for peak, 1.59 (1.08-2.33) for velocity, 0.92 (0.62-1.38) for lag time, and 1.21 (0.86-1.70) for time-to-peak. GlycA mediated only a small proportion of all observed associations. In conclusion, elevated levels of coagulation factor and thrombin generation potential are associated with incident type 2 diabetes, suggesting the involvement of hypercoagulability in the pathogenesis of type 2 diabetes.

Association between dietary magnesium intake, inflammation, and neurodegeneration

BackgroundConsistent evidence shows that magnesium (Mg) intake is associated with lower blood pressure (BP), and that lower BP is associated with improved cerebral health. However, recent findings indicate that the positive effect of dietary Mg intake on cerebral health is not mediated by a decrease in BP. As Mg’s anti-inflammatory action is a plausible alternative mechanism, the objective of this study was to investigate the associations between Mg intake and inflammation to determine whether it mediates any neuroprotective effect.MethodsParticipants from the UK Biobank (n = 5775, aged 40–73 years, 54.7% female) were assessed for dietary magnesium using an online food questionnaire, brain and white matter lesion (WML) volumes were segmented with FreeSurfer software, and inflammation markers including high-sensitivity C-reactive protein (hs-CRP), leukocyte, erythrocyte count, and Glycoprotein acetylation (GlycA) were measured using specific laboratory techniques such as immunoturbidimetry, automated cell counting, and nuclear magnetic resonance. Hierarchical linear regression models were performed to investigate the association between dietary Mg, and inflammatory markers and between dietary Mg, brain and WMLs volumes. Mediation analysis was performed to test a possible mediation role of inflammation on the association between dietary Mg and brain and WMLs volumes.ResultsHigher dietary Mg intake was associated with lower inflammation: hs-CRP level (− 0.0497%; 95% confidence interval [CI] − 0.0497%, − 0.0199%) leukocytes count (− 0.0015%; 95%CI − 0.00151%, − 0.0011%), and GlycA (− 0.0519%; 95%CI − 0.1298%, − 0.0129%). Moreover, higher dietary Mg intake was associated with larger grey matter volume (0.010%; 95%CI 0.004%, 0.017%), white matter volume (0.012%; 95%CI 0.003, 0.022) and right hippocampal volume (0.002%; 95%CI 0.0007, –0.0025%). Lower hs-CRP levels mediated the positive association between higher dietary Mg intake and larger grey matter volume.ConclusionsThe anti-inflammatory effects of dietary Mg intake in the general population, appears to mediate its neuroprotective effect.

Metabolites and depressive symptoms: Network- and longitudinal analyses from the Finnish Depression and Metabolic Syndrome in Adults (FDMSA) Study

BackgroundDepression is associated with metabolic abnormalities linked to metabolic syndrome and tissue inflammation, but the interplay between metabolic markers and their association with subsequent depression is unknown. Therefore, we aimed to describe the network of metabolites and their prospective association with depressive symptoms. MethodsThe Finnish Depression and Metabolic Syndrome in Adults (FDMSA) cohort, originally a prospective case-control study, comprised a group with Beck Depression Inventory (BDI)-I scores ≥10 at baseline, and controls (n = 319, BDI-I < 10); mean (sd) follow-up time: 7.4 (0.7) years. Serum metabolic biomarkers were determined by proton nuclear magnetic resonance (NMR), and depressive symptoms sum-score by using the BDI-I. We examined the prospective associations between metabolites at baseline and BDI score at follow-up utilizing multivariate linear regression, parsimonious predictions models and network analysis. ResultsSome metabolites tended to be either negatively (e.g. histidine) or positively associated (e.g. glycoprotein acetylation, creatinine and triglycerides in very large high density lipoproteins [XL-HDL-TG]) with depressive symptoms. None of the associations were significant after correction for multiple testing. The network analysis suggested high correlation among the metabolites, but that none of the metabolites directly influenced subsequent depressive symptoms. LimitationsAlthough the sample size may be considered satisfactory in a prospective context, we cannot exclude the possibility that our study was underpowered. ConclusionsOur results suggest that the investigated metabolic biomarkers are not a driving force in the development of depressive symptoms. These findings should be confirmed in studies with larger samples and studies that account for the heterogeneity of depressive disorders.

GlycA: Evaluation of a New Biomarker of Acute Pancreatitis.

Acute pancreatitis (AP) is a leading cause of gastrointestinal hospital admissions, with up to 40% mortality in patients with moderate-severe AP. Glycoprotein acetylation (GlycA) is measured as a nuclear magnetic resonance signal (NMR) of the post-translational modification of glycosylated acute-phase proteins released during inflammation. We aimed to investigate the role of GlycA as an inflammatory biomarker of AP. We prospectively enrolled 20 AP patients and 22 healthy controls and collected EDTA plasma samples at admission and discharge. NMR spectra were acquired from these samples using a 400 MHz Vantera® Clinical Analyzer, and GlycA concentrations were calculated (normal = 400 μmol/L). The GlycA NMR signal, at 2.00 ± 0.01 ppm in the NMR spectrum, is derived from the N-acetyl methyl group protons within the carbohydrate side chains of circulating glycoproteins such as α1-acid glycoprotein, haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin. GlycA levels were then compared between AP patients and controls, as well as within the AP group, based on etiology and severity. Demographic comparisons were similar, except for a higher BMI in AP patients compared to healthy controls (29.9 vs. 24.8 kg/m2; p < 0.001). AP was mild in 10 patients, moderate in 7, and severe in 3. GlycA levels were higher in AP patients than healthy controls on admission (578 vs. 376 μmol/L, p < 0.001) and at discharge (655 vs. 376 μmol/L, p < 0.001). GlycA levels were significantly higher in patients with moderate-severe AP than in those with mild AP at discharge (533 vs. 757 μmol/L, p = 0.023) but not at admission. After adjusting for BMI, multivariable regression indicated that patients with GlycA levels > 400 μmol/L had significantly higher odds of having AP of any severity (OR = 6.88; 95% CI, 2.07-32.2; p = 0.004) and mild AP (OR = 6.12; 95% CI, 1.48-42.0; p = 0.025) than controls. Our pilot study highlights the use of GlycA as a novel diagnostic biomarker of inflammation in patients with AP. Our study shows that GlycA levels were significantly higher in hospitalized AP patients compared to healthy controls. Patients with moderate-to-severe AP had higher GlycA levels compared to patients with mild AP at the time of their hospital discharge, suggesting persistent inflammation in patients with severe disease.

Combined Association of Novel and Traditional Inflammatory Biomarkers With Carotid Artery Plaque: GlycA Versus C-Reactive Protein (ELSA-Brasil)

Elevated levels of glycoprotein acetylation (GlycA) and C-reactive protein (CRP) have been associated with carotid artery plaque (CAP). However, it is not yet established if elevations in both inflammatory biomarkers provide incremental association with CAP. This study aimed evaluate the cross-sectional association of high CRP and GlycA with CAP at baseline participants from the ELSA-Brasil adult cohort. Participantswith information on CRP, GlycA, and CAP with neither previous cardiovascular disease nor CRP >10mg/L were included. High GlycA and CRP were defined as values within upper quintile and >3mg/L, respectively. Participants were classified into 4 groups: 1. nonelevated CRP/GlycA (reference group); 2. elevated CRP alone; 3. elevated GlycA alone; and 4. both elevated. The analysis included 4,126 participants with median age of 50 years-old, being 54.2% of women. Prevalence of CAP was 36.1%. Participants with high CRP had the highest frequency of obesity, whereas participants with high GlycA presented higher cardiovascular risk factor burden and were more likely to have CAP than the reference group (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.11 to 1.73), persisting after multivariable adjustment (OR 1.37, 95% CI 1.02 to 1.83). Participants with both elevated CRP and GlycA were more likely to have CAP in crude (OR 1.35, 95% CI 1.10 to 1.65) but not in adjusted models. The findings suggest potential different biologic pathways between inflammation and carotid atherosclerosis: high GlycA was associated with CAP whereas high CRP was more associated with obesity.

Association of Advanced Lipoprotein Subpopulation Profiles with Insulin Resistance and Inflammation in Patients with Type 2 Diabetes Mellitus.

Plasma lipoproteins exist as several subpopulations with distinct particle number and size that are not fully reflected in the conventional lipid panel. In this study, we sought to quantify lipoprotein subpopulations in patients with type 2 diabetes mellitus (T2DM) to determine whether specific lipoprotein subpopulations are associated with insulin resistance and inflammation markers. The study included 57 patients with T2DM (age, 61.14 ± 9.99 years; HbA1c, 8.66 ± 1.60%; mean body mass index, 35.15 ± 6.65 kg/m2). Plasma lipoprotein particles number and size were determined by nuclear magnetic resonance spectroscopy. Associations of different lipoprotein subpopulations with lipoprotein insulin resistance (LPIR) score and glycoprotein acetylation (GlycA) were assessed using multi-regression analysis. In stepwise regression analysis, VLDL and HDL large particle number and size showed the strongest associations with LPIR (R2 = 0.960; p = 0.0001), whereas the concentrations of the small VLDL and HDL particles were associated with GlycA (R2 = 0.190; p = 0.008 and p = 0.049, respectively). In adjusted multi-regression analysis, small and large VLDL particles and all sizes of lipoproteins independently predicted LPIR, whereas only the number of small LDL particles predicted GlycA. Conventional markers HbA1c and Hs-CRP did not exhibit any significant association with lipoprotein subpopulations. Our data suggest that monitoring insulin resistance-induced changes in lipoprotein subpopulations in T2DM might help to identify novel biomarkers that can be useful for effective clinical intervention.

Association of physical activity with metabolic profile from adolescence to adulthood.

Physical activity benefits cardiometabolic health, but little is known about its detailed links with serum lipoproteins, amino acids, and glucose metabolism at young age. We therefore studied the association of physical activity with a comprehensive metabolic profile measured repeatedly in adolescence. The cohort is derived from the longitudinal Special Turku Coronary Risk Factor Intervention Project. At ages 13, 15, 17, and 19 years, data on physical activity were collected by a questionnaire, and circulating metabolic measures were quantified by nuclear magnetic resonance metabolomics from repeatedly assessed serum samples (age 13: n=503, 15: n=472, 17: n=466, and 19: n=361). Leisure-time physical activity (LTPA;MET h/wk) was directly associated with concentrations of polyunsaturated fatty acids, and inversely with the ratio of monounsaturated fatty acids to total fatty acids (-0.006SD; [-0.008, -0.003]; p < 0.0001). LTPA was inversely associated with very-low-density lipoprotein (VLDL) particle concentration (-0.003SD; [-0.005, -0.001]; p=0.002) and VLDL particle size (-0.005SD; [-0.007, -0.003]; p < 0.0001). LTPA showed direct association with the particle concentration and size of high-density lipoprotein (HDL), and HDL cholesterol concentration (0.004SD; [0.002, 0.006]; p < 0.0001). Inverse associations of LTPA with triglyceride and total lipid concentrations in large to small sized VLDL subclasses were found. Weaker associations were seen for other metabolic measures including inverse associations with concentrations of lactate, isoleucine, glycoprotein acetylation, and a direct association with creatinine concentration. The results remained after adjusting for body mass index and proportions of energy intakes from macronutrients. Physical activity during adolescence is beneficially associated with the metabolic profile including novel markers. The results support recommendations on physical activity during adolescence to promote health and possibly reduce future disease risks.

Circulating cell-free DNA in health and disease — the relationship to health behaviours, ageing phenotypes and metabolomics

Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.

Social Jetlag Is Associated With Poor Diet and Increased Inflammation in the ZOE PREDICT 1 Cohort

ObjectivesSocial jetlag is a habitual pattern of short sleep on work days relative to longer, often later, ‘catch-up sleep’, on work-free days. This chronic pattern of inconsistent sleep times has been associated with poor dietary choices and unfavourable body weight and cardiometabolic health outcomes. We explored associations between social jetlag with dietary intake, body composition, and cardio-metabolic health in the densely phenotyped PREDICT 1 cohort. MethodsParticipants (n = 931) who self-reported habitual sleep on week-days and weekend days, (males, n = 258 and females, n = 673, aged 18–65 years) were identified from the ZOE PREDICT 1 study, a multi-centre dietary intervention study of 1002 healthy UK individuals (NCT03479866). Demographic information (age, gender, education level, ethnicity, menopausal status), habitual diet (FFQ), cardiometabolic blood biomarkers and postprandial responses to standardized test meals in clinic and free-living settings were collected. Social jetlag was calculated as a difference of ≥ 1.5 h in sleep midpoint on week versus weekend days. Differences in diet and cardiometabolic risk factors were tested (analysis of covariance) adjusting for sex, age, BMI, ethnicity and socio-economic status. ResultsOnly 3% (n = 26) of participants were short sleepers (< 7 h), 25% (n = 237) were long sleepers (> 9 h) and 16% (n = 145) had social jetlag. The social jetlag group had a higher proportion of males (39% vs 25%) and were younger (mean ± SD) (38.4 ± 11.3 y vs 46.8 ± 11.7 y). Social jetlag was associated with less healthy diets (healthy plant based dietary index) and lower intakes of fruits, nuts and number of plants consumed, as well as higher intakes of sugar-sweetened beverages (p < 0.05 for all). Fasting concentrations of glycoprotein acetylation (GlycA), a composite marker of systemic inflammation, was slightly higher (1.35 ± 0.19 mmol/L vs 1.32 ± 0.18 mmol/L, p = 0.034) in participants with social jetlag. ConclusionsOur findings support the complex relationship between sleep patterns, diet quality and markers of cardiometabolic health. Multi-factorial diet and lifestyle approaches are needed to improve health, now underpinned by emerging knowledge about the potential long-term impacts of modest circadian misalignments and low grade inflammation. Funding SourcesZOE Ltd.

Meal-induced inflammation: postprandial insights from the Personalised REsponses to DIetary Composition Trial (PREDICT) study in 1000 participants

ABSTRACTBackgroundMeal-induced metabolic changes trigger an acute inflammatory response, contributing to chronic inflammation and associated diseases.ObjectivesWe aimed to characterize variability in postprandial inflammatory responses using traditional (IL-6) and novel [glycoprotein acetylation (GlycA)] biomarkers of inflammation and dissect their biological determinants with a focus on postprandial glycemia and lipemia.MethodsPostprandial (0–6 h) glucose, triglyceride (TG), IL-6, and GlycA responses were measured at multiple intervals after sequential mixed-nutrient meals (0 h and 4 h) in 1002 healthy adults aged 18–65 y from the PREDICT (Personalised REsponses to DIetary Composition Trial) 1 study, a single-arm dietary intervention study. Measures of habitual diet, blood biochemistry, gut microbiome composition, and visceral fat mass (VFM) were also collected.ResultsThe postprandial changes in GlycA and IL-6 concentrations were highly variable between individuals. Participants eliciting an increase in GlycA and IL-6 (60% and 94% of the total participants, respectively) had mean 6-h increases of 11% and 190%, respectively. Peak postprandial TG and glucose concentrations were significantly associated with 6-h GlycA (r = 0.83 and r = 0.24, respectively; both P < 0.001) but not with 6-h IL-6 (both P > 0.26). A random forest model revealed the maximum TG concentration was the strongest postprandial TG predictor of postprandial GlycA and structural equation modeling revealed that VFM and fasting TG were most strongly associated with fasting and postprandial GlycA. Network Mendelian randomization demonstrated a causal link between VFM and fasting GlycA, mediated (28%) by fasting TG. Individuals eliciting enhanced GlycA responses had higher predicted cardiovascular disease risk (using the atherosclerotic disease risk score) than the rest of the cohort.ConclusionsThe variable postprandial increases in GlycA and their associations with TG metabolism highlight the importance of modulating TG in concert with obesity to reduce GlycA and associated low-grade inflammation–related diseases.This trial was registered at clinicaltrials.gov as NCT03479866.

Associations between Dietary Patterns and Inflammatory Markers during Pregnancy: A Systematic Review.

Elevated inflammation in pregnancy has been associated with multiple adverse pregnancy outcomes and potentially an increased susceptibility to future chronic disease. How maternal dietary patterns influence systemic inflammation during pregnancy requires further investigation. The purpose of this review was to comprehensively evaluate studies that assessed dietary patterns and inflammatory markers during pregnancy. This review was guided by the Preferred Reporting Items for Systematic Review and Meta-Analyses. Included studies were sourced from EMBASE, PubMed, Web of Science, and Scopus and evaluated using The Quality Assessment Tool for Quantitative Studies. Inclusion criteria consisted of human studies published in English between January 2007 and May 2020 that addressed associations between dietary patterns and inflammatory markers during pregnancy. Studies focused on a single nutrient, supplementation, or combined interventions were excluded. A total of 17 studies were included. Despite some inconsistent findings, maternal diets characterized by a higher intake of animal protein and cholesterol and/or a lower intake of fiber were shown to be associated with certain pro-inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF- α), IL-8, serum amyloid A (SAA), and glycoprotein acetylation (GlycA)). Future studies that explore a broader range of inflammatory markers in the pregnant population, reduce measurement errors, and ensure adequate statistical adjustment are warranted.

Distinct Metabolomic Profile Because of Gestational Diabetes and its Treatment Mode in Women with Overweight and Obesity.

Whether the presence of gestational diabetes (GDM) and its treatment mode influence the serum metabolic profile in women with overweight or obesity was studied. The serum metabolic profiles of 352 women with overweight or obesity participating in a mother-infant clinical study were analyzed with a targeted NMR approach (at 35.1 median gestational weeks). GDM was diagnosed with a 2-hour 75-g oral glucose tolerance test. The metabolomic profile of the women with GDM (n = 100) deviated from that of women without GDM (n = 252). Differences were seen in 70 lipid variables, particularly higher concentrations of very low-density lipoprotein particles and serum triglycerides were related to GDM. Furthermore, levels of branched-chain amino acids and glycoprotein acetylation, a marker of low-grade inflammation, were higher in women with GDM. Compared with women with GDM treated with diet only, the women treated with medication (n = 19) had higher concentrations of severalizes of VLDL particles and their components, leucine, and isoleucine, as well as glycoprotein acetylation. A clearly distinct metabolic profile was detected in GDM, which deviated even more if the patient was receiving medical treatment. This suggests a need for more intense follow-up and therapy for women with GDM during pregnancy and postpartum to reduce their long-term adverse health risks.

Metformin and insulin treatment of gestational diabetes: effects on inflammatory markers and IGF-binding protein-1 \u2013 secondary analysis of a randomized controlled trial

BackgroundGestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation. We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes.MethodsThis is a secondary analysis of a previous randomized controlled trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum samples were collected at the time of diagnosis (baseline, mean 30 gestational weeks [gw]) and at 36 gw. Inflammatory markers serum high-sensitivity CRP (hsCRP), interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and glycoprotein acetylation (GlycA) as well as three IGFBP-1 phosphoisoform concentrations were determined.ResultsIn the metformin and insulin groups combined, hsCRP decreased (p = 0.01), whereas IL-6 (p = 0.002), GlycA (p < 0.0001) and all IGFBP-1 phosphoisoforms (p < 0.0001) increased from baseline to 36 gw. GlycA (p = 0.02) and non-phosphorylated IGFBP-1 (p = 0.008) increased more in patients treated with metformin than those treated with insulin. Inflammatory markers did not clearly associate with pregnancy outcomes but non-phosphorylated IGFBP-1 was inversely associated with gestational weight gain.ConclusionsMetformin had beneficial effects on maternal serum IGFBP-1 concentrations compared to insulin, as increased IGFBP-1 related to lower total and late pregnancy maternal weight gain. GlycA increased more during metformin treatment compared to insulin. The significance of this observation needs to be more profoundly examined in further studies. There were no evident clinically relevant relations between inflammatory markers and pregnancy outcome measures.Trial registrationThe trial comparing metformin and insulin treatment was registered in ClinicalTrials.gov (NCT01240785) November 3, 2010. Retrospectively registered.

Prospective associations between hsCRP and GlycA inflammatory biomarkers and depression: The Brazilian longitudinal study of adult health (ELSA-Brasil)

BackgroundAlthough low-grade inflammation is associated with onset and persistence of depression, most biomarkers display modest predictive effects. GlycA (glycoprotein acetylation) is a unique metabolomic composite of pro-inflammatory acute-phase glycoproteins. We hypothesized that GlycA levels would predict depression incidence, remission and persistence, with higher accuracy than high-sensitivity c-reactive protein (hsCRP). We also explored the additive predictive value of GlycA above and beyond hsCRP. MethodsCohort design using the sample of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)'s São Paulo site. Baseline GlycA and hsCRP levels were measured in blood plasma. Depression incidence, remission, and persistence were assessed using the Clinical Interview Scheduled Revised (CIS-R) at two time points separated by a mean of 3.8 years. Multivariable Poisson, logistic and linear regression models were used for prediction. Models were adjusted for sociodemographic and clinical confounders, including age, gender, ethnicity, education, cardiovascular assessments, antidepressant and anti-inflammatory drug use, anxiety disorders, alcohol use, and body mass index. ResultsWe included 4,364 participants (53.2% females, mean age 51.4 ± 8.9 years) with no autoimmune disorders. GlycA robustly predicted depression persistence (relative risk of 7.28, 95% confidence interval 1.33–45.57, p = 0.023 in the fully-adjusted model), but not depression onset. Although hsCRP also predicted depression persistence, its effects were fully explained by confounders and by GlycA levels. GlycA also predicted worsening of depressive symptoms in depressed patients and depression persistence vs. remission in fully-adjusted models. LimitationsBrief depressive episodes could not be measured by our assessments. ConclusionsGlycA might be a new inflammatory prognosis biomarker for depression.

Serum GlycA Level is Elevated in Active Systemic Lupus Erythematosus and Correlates to Disease Activity and Lupus Nephritis Severity.

Objective: Reliable non-invasive biomarkers are needed to assess disease activity and prognosis in patients with systemic lupus erythematosus (SLE). Glycoprotein acetylation (GlycA), a novel biomarker for chronic inflammation, has been reported to be increased in several inflammatory diseases. We investigated the relevance of serum GlycA in SLE patients exhibiting various levels of activity and severity, especially with regards to renal involvement. Methods: Serum GlycA was measured by nuclear magnetic resonance spectroscopy in samples from well characterized SLE patients and from both healthy controls and patients with other kidney diseases (KD). Disease activity was evaluated using the Systemic Lupus Erythematosus Activity Index 2000 (SLEDAI-2K). Renal severity was assessed by kidney biopsy. Results: Serum GlycA was elevated in active (n = 105) compared to quiescent SLE patients (n = 39, p < 10−6), healthy controls (n = 20, p = 0.009) and KD controls (n = 21, p = 0.04), despite a more severely altered renal function in the latter. GlycA level was correlated to disease activity (SLEDAI-2K, ρ = 0.37, p < 10−4), C-reactive protein, neutrophil count, triglyceride levels, proteinuria and inversely to serum albumin. In patients with biopsy-proven lupus nephritis (LN), GlycA levels were higher in proliferative (n = 26) than non-proliferative LN (n = 10) in univariate analysis (p = 0.04), and was shown to predict proliferative LN independently of renal parameters, immunological activity, neutrophil count and daily corticosteroid dosage by multivariate analysis (p < 5 × 10−3 for all models). In LN patients with repeated longitudinal GlycA measurement (n = 11), GlycA varied over time and seemed to peak at the time of the flare. Conclusions: GlycA, as a summary measure for different inflammatory processes, could be a valuable biomarker of disease activity in patients with SLE, and a non-invasive biomarker of pathological severity in the context of LN.

Association of lipoprotein subfractions and glycoprotein acetylation with coronary plaque burden in SLE

ObjectiveSubjects with SLE display an enhanced risk of atherosclerotic cardiovascular disease (CVD) that is not explained by Framingham risk. This study sought to investigate the utility of nuclear MR (NMR)...

Metabolic profiling of adherence to diet, physical activity and body size recommendations for cancer prevention

Maintaining a healthy body weight, eating well and being physically active lowers cancer risk by 30%. However, the biology underlying these relationships is not well understood. We examined cross-sectional associations between metabolites and cancer preventive behaviors as well as the relevance to cancer-related pathways among 120 participants (50% men, mean BMI 26.6 kg/m2, mean age 54 years) with no history of smoking or cancer. Participants completed questionnaires, physical measurements and provided blood samples. Non-targeted nuclear magnetic resonance captured 223 metabolite measures. Factor analysis was performed separately for amino acid, fatty acid and lipoprotein groups. Multivariable-adjusted linear regression was used to evaluate associations between cancer preventive recommendations and metabolite-containing factors (p-value < 0.05, false discovery rate <0.20). An inflammation-related metabolite (glycoprotein acetylation) loaded strongly on a factor that was associated with excess adiposity (body fat ≥25% (men) or ≥30% (women) ß (SE) = 0.74 (0.18)) and not meeting physical activity recommendations (ß (SE) = 0.40 (0.20)). Insulin sensitivity-related metabolites including monounsaturated and polyunsaturated fats were lower among participants not meeting recommendations for adiposity, fruits and vegetables and physical activity while branched chain amino acids were higher. Cancer preventive behaviors were associated with complex metabolic signatures, including alterations in pathways known to be involved in cancer pathogenesis.

Dietary intake of fat and fibre according to reference values relates to higher gut microbiota richness in overweight pregnant women - CORRIGENDUM.

The diet-microbiota-metabolism relationships during pregnancy are mostly unknown. We explored the effect of the habitual diet and adherence to the dietary reference values on gut microbiota composition and diversity. Further, the association of gut microbiota with serum lipidomics and low-grade inflammation was evaluated. Overweight and obese women (BMI 30·7 (sd 4·4) kg/m2, n 100) were studied at early pregnancy (≤17 weeks). Intakes of nutrients were calculated from 3-d food diaries. Faecal microbiota composition was analysed using 16S rRNA gene sequencing. Fasting serum lipidomic profiles were determined by NMR. High-sensitivity C-reactive protein, glycoprotein acetylation (GlycA) and lipopolysaccharide activity were used as markers for low-grade inflammation. The recommended dietary intake of fibre and fat was related to higher gut microbiota richness and lower abundance of Bacteroidaceae. Correlations were observed between gut microbiota richness and GlycA and between a few microbiota genera and serum lipoprotein particles. As a conclusion, adherence to the dietary reference intake of fat and fibre was associated with beneficial gut microbiota composition, which again contributed to lipidomic profile. Higher gut microbiota richness and nutrient intakes were linked to a lower level of low-grade inflammation marker GlycA. This finding offers novel insights and opportunities for dietary modification during pregnancy with potential of improving the health of the mother and the child.

Increased glycoprotein acetylation is associated with high cardiac event rates: Analysis using coronary computed tomography angiography.

Objective:Glycoprotein acetylation (GlycA), an emerging inflammatory biomarker, has been used as an indicator of cardiovascular disease. Our research aimed to evaluate the correlation between GlycA and coronary artery disease (CAD) using coronary computed tomography angiography (CCTA).Methods:In the present study, a total of 342 patients were enrolled, and each of them underwent CCTA. The correlation between GlycA and major adverse cardiac events (MACE) was detected via Cox’s proportional hazards models. Based on differences in the GlycA level, patients were categorized into three groups (T1, T2, and T3).Results:Compared with the group with the lowest GlycA level (T1), the group with the highest GlycA level (T3) exhibited stronger atherosclerotic pressure involving the extent of atherosclerotic plaque and risk of obstructive CAD. In addition, the patients in the T3 group had a greater chance of experiencing MACE and higher all-cause mortality than those in the T1 group. Among patients without CAD who underwent CCTA, those with high GlycA levels experienced elevated atherosclerotic stress and heightened risk of MACE compared with those with low GlycA levels.Conclusion:These results suggest that serum GlycA is significantly associated with the long-term clinical results of patients with no known CAD undergoing CCTA. The risks of death and experiencing MACE increase among patients with high GlycA levels.

Статистика фамилий в СССР в начале XX века

В обзоре представлены данные о недавно (2015 г.) выявленном предикторе смерти, независимо от причин её вызывающих. На роль предиктора смерти претендует продукт ацетилирования гликопротеинов - GlycA (N-acetylglucosamine/galactosamine). Обсуждаются тонкие механизмы действия GlycA при воспалении, сердечно-сосудистой патологии, онкологических заболеваниях и диабете 2-го типа. Выявлены тесные корреляционные связи между содержанием GlycA и резистентностью к инсулину. С возрастом и увеличением массы тела (ИМТ) содержание GlycA повышается. Высокие концентрации GlycA обратно пропорциональны объему памяти и скорости обработки информации. This review presents data on a recently discovered (2015) predictor for death regardless of its cause, a glycoprotein acetylation product, GlycA (biomarker of protein glycan N-acetyl groups). Subtle mechanisms of GlycA action in inflammation, cardiovascular diseases, cancer, and type 2 diabetes are discussed. A strong correlation of GlycA content with insulin resistance was found. The GlycA content increases with increasing age and body weight (BWI). High concentrations of GlycA are inversely proportional to global cognition, memory, and speed of information processing.