Preeclampsia (PE) and fetal growth restriction (FGR) are both placenta-mediated disorders with unclear pathogenesis. Metabolomics of maternal and fetal pairs might help in understanding these ...disorders. We recruited prospectively pregnancies with normotensive FGR, PE without FGR, PE + FGR and uncomplicated pregnancies as controls. Nuclear magnetic resonance metabolomics were applied on plasma samples collected at delivery. Advanced lipoprotein, glycoprotein and choline profiling was performed using the Liposcale test. The software package Dolphin was used to quantify 24 low-molecular-weight metabolites. Statistical analysis comprised the comparison between each group of complicated pregnancies versus controls, considering 5% false discovery rate correction. Lipid profiles were altered in accordance with the clinical presentation of these disorders. Specifically, PE mothers and FGR fetuses (with or without FGR or PE, respectively) exhibited a pro-atherogenic and pro-inflammatory profile, with higher concentrations of triglycerides, remnant cholesterol (VLDL, IDL) and Glc/GalNAc-linked and lipid-associated glycoproteins compared to controls. Low-molecular-weight metabolites were extensively disturbed in preeclamptic mothers, with or without FGR. Growth restricted fetuses in the presence of PE showed changes in low-molecular-weight metabolites similar to their mothers (increased creatine and creatinine), while normotensive FGR fetuses presented scarce differences, consistent with undernutrition (lower isoleucine). Further research is warranted to clarify maternal and fetal adaptations to PE and FGR.
A 10-month strategy of cardiac telerehabilitation (CTR) improved outcomes over a standard centre-based cardiac rehabilitation (CBCR), as recently published. We hypothesised that prolonged ...telerehabilitation could also improve proinflammatory status and lipoprotein particle composition.
A randomised controlled trial compared a prolonged CTR program with CBCR in post-ACS patients. Patient's age was 18–72 years with low-risk criteria. Blood samples were drawn at baseline, at 4- and 10-months follow-up. Advanced lipoprotein characterization was performed using the NMR-based Liposcale test. Signals from glycoproteins (GlycA and GlycB) were also assessed.
The final analysis included 31 patients in the CTR group and 25 patients in the CBCR group. GlycA decreased in the CTR group (p = 0,007). LDL particle number (LDL-P) increase in both groups, but it was at the expense of small-sized LDL in the CBCR group (p = 0.012). Triglycerides in intermediate-density lipoprotein (IDL-TG) increased only in the CBCR group (p = 0.043). The triglyceride-to-HDL (TG/HDL) ratio decreased only in the CTR group (p = 0.006). The TG/HDL ratio was correlated with GlycA (Spearman's correlation coefficient: 0.558, p < 0.001) but not with CRP (p = 0.101).
Our results showed that a 10-month CTR program reduced GlycA levels, the TG/HDL ratio and avoided unfavourable long-term changes in lipoprotein particle composition.
Registration at ClinicalTrials.gov. NCT number: 04942977
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•GlycA levels are associated with risk of new coronary events and mortality.•Small lipoprotein particles are associated with atherosclerosis progression.•Extended cardiac telerehabilitation reduced GlycA levels.•Extended cardiac telerehabilitation prevented unfavourable lipoprotein changes.•These results could modify rehabilitation protocols if confirmed subsequently.
The role of inflammation in heart failure (HF) has been extensively described, but it is uncertain whether inflammation exerts a different prognostic influence according to etiology. We aimed to ...examine the inflammatory state in chronic HF by measuring N-acetylglucosamine/galactosamine (GlycA) and sialic acid (GlycB), evolving proton nuclear magnetic resonance biomarkers of systemic inflammation, and explore their prognostic value in patients with chronic HF. The primary end point was a composite of all-cause death and HF readmission. A total of 429 patients were included. GlycB correlated with interleukin-1 receptor-like 1 in the whole cohort (r2 = 0.14, p = 0.011) and the subgroup of nonischemic etiology (r2 = 0.31, p <0.001). No association was found with New York Heart Association functional class or left ventricular ejection fraction. In patients with nonischemic HF (52.2%, n = 224), GlycA and GlycB exhibited significant association with the composite end point (hazard ratio HR 1.19, 95% confidence interval CI 1.06 to 1.33, p = 0.004 and HR 2.13, 95% CI 1.43 to 3.13, p <0.001; respectively) and GlycB with HF readmission after multivariable adjustment (HR 2.25, 95% CI 1.54 to 3.30, p <0.001). GlycB levels were also associated with a greater risk of HF-related recurrent admissions (adjusted incidence rate ratio 1.33, 95% CI = 1.07 to 1.65, p = 0.009). None of the markers were associated with the clinical end points in patients with ischemic HF. In conclusion, GlycA and GlycB represent an evolving approach to inflammation status with prognostic value in long-term outcomes in patients with nonischemic HF.
Abstract
Objectives
To identify potential biomarkers of disease activity analysing the proteome of high-density lipoprotein (HDL) particles from SLE patients in clinical remission and when they ...develop a flare compared with a healthy control group.
Methods
Quantitative proteomic analyses of purified HDL were performed using Tandem Mass Tag isobaric tag-labelling and nanoLC-Orbitrap (nLC-MS/MS) from nine SLE patients in clinical remission when they developed a flare and from nine healthy controls (9–9-9). We verified the identified proteins by Western blot and ELISA in a cohort of 104 SLE women patients, 46 healthy women and 14 SLE patients when a flare developed.
Results
We found 17 proteins with a significant fold-change (>1.1) compared with the control group. In lupus patients experiencing a flare compared with those in remission, we identified four proteins with a significant fold-change (C4, Indian Hedgehog protein, S100A8 and gelsolin). Plasma gelsolin (pGSN) levels were decreased in the 104 SLE patients (176.02(74.9) mcg/l) compared with the control group (217.13(86.7) mcg/l); P=0.005 and when they developed a clinical flare (104.84(41.7) mcg/l); P=0.002). pGSN levels were associated with HDL cholesterol levels (r = 0.316, P<0.001). Antimalarial treated patients showed significant higher levels of pGSN (214.56(88.94) mcg/l regarding 170.35(66.36) mcg/l); P = 0.017.
Conclusion
Decreased pGSN are associated with clinical disease activity in SLE patients. Antimalarial treatment and HDL cholesterol are associated with higher levels of pGSN.
Background Supplementation with omega-3 (n-3) fatty acid or dietary fish may protect against atherosclerosis, but the potential mechanisms are unclear. Prior studies found modest ...triglyceride-lowering effects and slight increases in LDL (low-density lipoprotein) cholesterol. Limited evidence has examined n-3 effects on more detailed lipoprotein biomarkers. Methods and Results We conducted a study of 26 034 healthy women who reported information on fish and n-3 intake from a 131-item food-frequency questionnaire. We measured plasma lipids, apolipoproteins, and nuclear magnetic resonance spectroscopy lipoproteins and examined their associations with dietary intake of fish, total n-3, and the n-3 subtypes (eicosapentaenoic, docosahexaenoic, and α-linolenic acids). Top- versus bottom-quintile intake of fish and n-3 were significantly associated with lower triglyceride and large VLDL (very-low-density lipoprotein) particles. Fish intake, but not total n-3, was positively associated with total cholesterol, LDL cholesterol, apolipoprotein B, and larger LDL size, but only α-linolenic acid was associated with lower LDL cholesterol. Total n-3, docosahexaenoic acid, and α-linolenic acid intake were also positively associated with larger HDL (high-density lipoprotein) size and large HDL particles. High eicosapentaenoic acid intake was significantly associated with only a decreased level of VLDL particle concentration and VLDL triglyceride content. The n-3 fatty acids had some similarities but also differed in their associations with prospective cardiovascular disease risk patterns. Conclusions Higher consumption of fish and n-3 fatty acids were associated with multiple measures of lipoproteins that were mostly consistent with cardiovascular prevention, with differences noted for high intake of eicosapentaenoic acid versus docosahexaenoic acid and α-linolenic acid that were apparent with more detailed lipoprotein phenotyping. These hypothesis-generating findings warrant further study in clinical trials. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.
Cocoa constitutes one of the richest sources of dietary flavonoids with demonstrated anti-diabetic potential. However, the metabolic impact of cocoa intake in a diabetic context remains unexplored. ...In this study, metabolomics tools have been used to investigate the potential metabolic changes induced by cocoa in type 2 diabetes (T2D). To this end, male Zucker diabetic fatty rats were fed on standard (ZDF) or 10% cocoa-rich diet (ZDF-C) from week 10 to 20 of life. Cocoa supplementation clearly decreased serum glucose levels, improved glucose metabolism and produced significant changes in the urine metabolome of ZDF animals. Fourteen differential urinary metabolites were identified, with eight of them significantly modified by cocoa. An analysis of pathways revealed that butanoate metabolism and the synthesis and degradation of branched-chain amino acids and ketone bodies are involved in the beneficial impact of cocoa on diabetes. Moreover, correlation analysis indicated major associations between some of these urine metabolites (mainly valine, leucine, and isoleucine) and body weight, glycemia, insulin sensitivity, and glycated hemoglobin levels. Overall, this untargeted metabolomics approach provides a clear metabolic fingerprint associated to chronic cocoa intake that can be used as a marker for the improvement of glucose homeostasis in a diabetic context.
Renal complications are the major cause of morbidity and mortality in patients with familial lecithin-cholesterol acyltransferase (LCAT) deficiency (FLD). We report three FLD patients, two of them ...siblings-only one of whom developed renal disease-and the third case being a young man with early renal disease. The aim of this study was to analyze the clinical characteristics and possible mechanisms associated with renal disease in these patients. Plasma lipid levels, LCAT activity, lipoprotein particle profile by NMR and FPLC, free and esterified cholesterol, presence of lipoprotein X (LpX) and DNA sequencing in the three FLD patients have been determined. The three cases presented clinical characteristics of FLD, although only one of the siblings developed renal disease, at 45 years of age, while the other patient developed the disease in his youth. Genetic analysis revealed new missense homozygous mutations, p.(Ile202Thr) in both siblings and p.(Arg171Glu) in the other patient. Lipoprotein particle analysis showed that the two patients with renal disease presented higher numbers of small very low-density lipoprotein (VLDL) and a higher concentration of triglycerides in VLDL. This study reports three new cases of LCAT deficiency, not previously described. Renal disease is not only dependent on LCAT deficiency, and could be due to the presence of VLDL particles, which are rich in triglycerides, free cholesterol and LpX.
While cholesterol content in high-density lipoproteins (HDLs) is a well-established inverse marker of cardiovascular risk, the importance of HDL-triglyceride (HDL-TG) concentration is not well known. ...We aim to examine plasma HDL-TG concentrations, assessed by
H-NMR, in patients with metabolic diseases and their association with classical biomarkers. In this cross-sectional study, we included 502 patients with type 2 diabetes or metabolic syndrome attending the lipid unit of our University Hospital. The presence of arteriosclerotic plaques was assessed by ultrasonography. A complete lipoprotein profile was performed by
H-NMR (Liposcale test). HDL-TG was strongly positively correlated with total triglycerides, glycerol, and fatty liver index, while a strong negative correlation was observed with HDL-cholesterol (HDL-C) and HDL-particle number (HDL-P). HDL-TG was associated with all triglyceride-rich lipoprotein parameters and had an opposite association with HDL-C and HDL-P. It was also significantly correlated with circulating cholesterol ester transfer protein (CETP). HDL-TG concentrations were higher as metabolic syndrome components increased. HDL-TG was also higher with worsening glucose metabolism. Patients with carotid plaques also showed higher HDL-TG. In contrast to HDL-C, HDL-TG is directly associated with metabolism and arteriosclerotic vascular alterations. HDL-TG should be considered a biomarker of metabolic and cardiovascular risk and could be a marker of HDL dysfunction.
This study aimed to assess whether the advanced characteristics of serum lipoprotein subclasses could better predict the risk of developing diabetic retinopathy (DR) and its severity compared to ...other established risk factors in subjects with type 1 (T1D) and type 2 (T2D) diabetes. This observational, cross-sectional substudy analyzed DR-related data from 309 T1D and 264 T2D subjects. The advanced lipoprotein and glycoprotein profile was determined by nuclear magnetic resonance (NMR) spectroscopy (Liposcale test). NMR analysis of lipoproteins revealed that T1D subjects with DR showed standard non-HDL particles, despite higher IDL lipid concentrations. Notably, IDL lipids were elevated in T1D subjects with worsened DR. VLDL and LDL were smaller, whereas HDL triglycerides were increased in DR compared with non-DR. On the other hand, the T2D subjects with DR showed altered characteristics in the LDL fraction, mainly revealed by a significant decrease in smaller LDL and a reduction in LDL-C. Moreover, the glycoprotein profile did not reveal significant changes among DR groups, regardless of the type of diabetes. However, lipoprotein characteristics and glycoproteins unveiled by NMR analysis did not improve the predictive value of conventional lipids or other traditional, well-established biomarkers of DR in our cohorts.
Abstract
Background and aim
Circulating biomarkers of metabolic and cardiovascular diseases can help in the early detection and prevention of those diseases. Using proton nuclear magnetic resonance ...(1H-NMR), we aimed to study the plasma levels of low-molecular-weight metabolites (LMWMs) in a cohort of 307 patients with metabolic diseases to assess their relationships with type-2 diabetes (T2D) and incident atherosclerotic cardiovascular disease (ASCVD).
Methods
We conducted a cross-sectional and prospective study. We included 307 patients attending the Lipid Unit of our University Hospital for the treatment of the following metabolic disturbances and associated disorders: T2D (73.9%), obesity (58.7%), and hypertension (55.1%). 1H-NMR was used to study the plasma levels of 13 LMWMs. LMWM serum concentrations were evaluated in patients with and without T2D. and the correlations with several parameters and their associations with T2D were analyzed. The association between LMWM levels at baseline and the development of ASCVD in patients with T2D after 10 years of follow-up was also evaluated.
Results
Among the LMWMs measured, the branched-chain amino acids (BCAAs) valine, leucine and isoleucine showed a positive association with several clinical and lipid-related biochemical parameters and inflammatory markers (p < 0.05). Likewise, these three BCAAS were associated with diabetes even after adjusting for covariates (p < 0.05). During the follow-up period of 10 years, 29 of the 185 patients with diabetes at baseline (15.68%) developed ASCVD. After adjusting for clinical covariates, baseline levels of valine and alanine were associated with the development of ASCVD (p < 0.05).
Conclusion
Overall, our results indicated that plasma levels of LMWMs measured by 1H-NMR could be potential biomarkers associated with T2D. Moreover, alanine and valine can help in the early detection of the cardiovascular risk associated with this metabolic disease.
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