Abstract
High-density lipoprotein cholesterol (HDL-C) is not a homogenous lipid fraction, but it can be further divided into subfractions. It is well-known that the Roma population has a high ...prevalence of reduced HDL-C levels and cardiovascular diseases (CVDs). However, it is unknown how this reduction affects different HDL subfractions, and whether changes in their quantity/representation are associated with an increased cardiovascular risk among them. In the present study, the HDL subfraction profile of the Hungarian general (HG) and the Roma populations were compared, and the subfractions showing a significant difference between the two populations were identified. The association of HDL subfractions with CVD risk estimated by the Framingham risk score (FRS) and the Systematic COronary Risk Evaluation (SCORE) algorithms were also defined. The present study is the first to find a significant association between HDL subfractions and cardiovascular risk estimated by FRS and SCORE. Ten HDL subfractions were investigated on small but carefully selected samples comprising 100 control subjects (with normal lipid profile) and 277 case subjects (with reduced HDL-C levels) from HG and Roma populations of a complex health survey. The level of HDL-1 to 3 subfractions and HDL-L showed a significant inverse association with cardiovascular risk estimated by both SCORE and FRS algorithms, whereas HDL-4 to 6 and HDL-I only for FRS. A higher representation (in %) of HDL-1 to 3 has a significant risk-reducing effect, while HDL-8 to 10 has a risk-increasing effect estimated by FRS. Our results confirmed that reduced levels of HDL-6 and -7 expressed in mmol/L were significantly associated with Roma ethnicity.
Betatrophin, also known as angiopoietin-like protein 8 (ANGPTL8), mainly plays a role in lipid metabolism. To date, associations between betatrophin and lipoprotein subfractions are poorly ...investigated. For this study, 50 obese patients with type 2 diabetes (T2D) and 70 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index (BMI) as well as 49 gender- and age-matched healthy, normal-weight controls were enrolled. Serum betatrophin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint gel electrophoresis. Betatrophin concentrations were found to be significantly higher in the T2D and NDO groups compared to the controls in all subjects and in females, but not in males. We found significant positive correlations between triglyceride, very low density lipoprotein (VLDL), large LDL (low density lipoprotein), small LDL, high density lipoprotein (HDL) -6-10 subfractions, and betatrophin, while negative correlations were detected between betatrophin and IDL, mean LDL size, and HDL-1-5. Proportion of small HDL was the best predictor of betatrophin in all subjects. Small LDL and large HDL subfractions were found to be the best predictors in females, while in males, VLDL was found to be the best predictor of betatrophin. Our results underline the significance of serum betatrophin measurement in the cardiovascular risk assessment of obese patients with and without T2D, but gender differences might be taken into consideration.
Type 2 diabetes mellitus (T2DM) is a major global public health problem, as it is associated with increased morbidity, mortality, and healthcare costs. Insulin resistance (IR) is a condition ...characterized by disturbances in carbohydrate and lipid metabolism that precedes T2DM. The aim of the present study was to investigate the association between HDL and its subfraction profile and the progression of IR, as assessed by the Homeostatic Model Assessment for IR (HOMA-IR) index, and to define cut-off values to identify an increased risk of IR. Individuals with a HOMA-IR greater than 3.63 were considered to have IR. The HDL subfractions were separated using the Lipoprint system, which identifies ten subfractions (HDL-1-10) in three subclasses as large (HDL-L), intermediate (HDL-I) and small (HDL-S). Analyses were performed on samples from 240 individuals without IR and 137 with IR from the Hungarian general and Roma populations. The HDL-1 to -6 subfractions and the HDL-L and -I classes showed a significant negative association with the progression and existence of IR. Among them, HDL-2 (B = −40.37, p = 2.08 × 10−11) and HDL-L (B = −14.85, p = 9.52 × 10−10) showed the strongest correlation. The optimal threshold was found to be 0.264 mmol/L for HDL-L and 0.102 mmol/L and above for HDL-2. Individuals with HDL-L levels below the reference value had a 5.1-fold higher risk of IR (p = 2.2 × 10−7), while those with HDL-2 levels had a 4.2-fold higher risk (p = 3.0 × 10−6). This study demonstrates that the HDL subfraction profile (especially the decrease in HDL-2 and -L) may be a useful marker for the early detection and intervention of atherogenic dyslipidemia in subjects with impaired glucose and insulin metabolism.
Oxidative stress and chronic low-grade inflammation are major characteristics of obesity-related disorders. The dominance of pro-oxidant and pro-inflammatory mechanisms triggers insulin resistance ...and enhances the progression of atherosclerosis. Discovered first as an esterase that hydrolyze organophosphates, human paraoxonase-1 is bound to high-density lipoprotein and inhibits the oxidation of lipoproteins and reduces the degree of inflammation, hence it is considered to act against atherosclerosis. In contrast, the majority of the adipokines secreted from the enlarged white adipose tissue promote the atherosclerotic process; and altered adipokine secretion is now regarded as one of the major contributors of increased cardiovascular morbidity and mortality in obesity. In this review, we detail the correlations between paraoxonase-1 and some selected adipokines, namely leptin, adiponectin and chemerin. Adipokine imbalance leads to decreased paraoxonase-1 activity that results in enhanced atherosclerosis; therefore, altered adipokine secretion may be predictive of cardiovascular complications in obesity. As an active organ secreting biological active substances, white adipose tissue may also act as a “fine-tuner” of immune and endocrine actions attenuating or enhancing reactions triggered by pathogens, inflammation and metabolic stimuli; and obesity, as a chronic noxious state may perturb the proper functioning of this fine-tuning process. Further investigations are of major importance to elucidate the associations between adipokines and paraoxonase-1 and to establish accurate interventions against obesity-related disorders.
•White adipose tissue-derived adipokine secretion is altered in obesity.•Imbalance in adipokines leads to increased cardiovascular risk.•Adipokine imbalance results in decreased paraoxonase-1 activity.•Adipokines may serve as fine-tuners of metabolic and immune processes.
Altered organokine expression contributes to increased cardiometabolic risk in obesity. Our aim was to evaluate the associations of serum afamin with glucose homeostasis, atherogenic dyslipidemia, ...and other adipokines in severe obesity to clarify the early metabolic alterations. 106 non-diabetic obese (NDO) subjects and 62 obese patients with type 2 diabetes matched for age, gender, and body mass index (BMI) were enrolled in this study. We compared their data with 49 healthy, lean controls. Serum afamin and retinol-binding protein 4 (RBP4), as well as plasma plasminogen activator inhibitor-1 (PAI-1), were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint gel electrophoresis. Afamin and PAI-1 found to be significantly higher in the NDO and T2M group (
< 0.001 and
< 0.001, respectively) than in the controls. In contrast, RBP4 was unexpectedly lower in the NDO and T2DM group compared to controls (
< 0.001). Afamin showed negative correlations with mean LDL size and RBP4, but positive correlations with anthropometric, glucose/lipid parameters, and PAI-1 in both the overall patients and the in NDO + T2DM groups. BMI, glucose, intermediate HDL, and small HDL were predictors of afamin. Afamin may serve as a biomarker for the severity of cardiometabolic disturbances in obesity. The complexity of organokine patterns in NDO subjects draws attention to the diverse spectrum of obesity-related comorbidities.
Cholesteryl ester transfer protein (
) is known to influence HDL-C levels, potentially altering the profile of HDL subfractions and consequently cardiovascular risk (CVR). This study aimed to ...investigate the effect of five single-nucleotide polymorphisms (SNPs; rs1532624, rs5882, rs708272, rs7499892, and rs9989419) and their haplotypes (H) in the
gene on 10-year CVR estimated by the Systematic Coronary Risk Evaluation (SCORE), the Framingham Risk Score for Coronary Heart Disease (FRS
) and Cardiovascular Disease (FRS
) algorithms. Adjusted linear and logistic regression analyses were used to investigate the association of SNPs and 10 haplotypes (H1-H10) on 368 samples from the Hungarian general and Roma populations. The T allele of rs7499892 showed a significant association with increased CVR estimated by FRS. H5, H7, and H8 showed a significant association with increased CVR based on at least one of the algorithms. The impact of H5 was due to its effect on TG and HDL-C levels, while H7 showed a significant association with FRS
and H8 with FRS
mediated by a mechanism affecting neither TG nor HDL-C levels. Our results suggest that polymorphisms in the
gene may have a significant effect on CVR and that this is not mediated exclusively by their effect on TG and HDL-C levels but also by presently unknown mechanisms.
Rheumatoid arthritis and metabolic syndrome Kerekes, György; Nurmohamed, Michael T; González-Gay, Miguel A ...
Nature reviews. Rheumatology,
11/2014, Letnik:
10, Številka:
11
Journal Article
Recenzirano
Rheumatoid arthritis (RA), especially active disease, is associated with considerable changes in body composition, lipids, adipokines and insulin sensitivity. Metabolic changes, such as increased ...total cholesterol, LDL cholesterol and triglyceride levels, occur even in preclinical RA. Active RA is associated with decreased lipid levels, BMI, fat and muscle mass, as well as altered lipid profiles. Some of these changes are also seen in metabolic syndrome, and could increase cardiovascular mortality. Importantly, the systemic inflammation underlying RA is an independent risk factor for cardiovascular disease. This Perspectives article summarizes data on the associations of various components of metabolic syndrome with RA, and discusses the effects of biologic therapy on these factors. The authors propose that components of metabolic syndrome should be monitored in patients with RA throughout the disease course, and argue that optimal disease control using biologic agents might attenuate several adverse effects of metabolic syndrome in these patients.
We aimed to investigate serum amino-terminal C-type natriuretic peptide (NT-proCNP) and its relationship with quantitative and qualitative HDL-parameters in patients with end-stage renal disease ...(ESRD) before, then 1 and 6 months after kidney transplantation (TX). Seventy patients (47 males, 23 females, mean age 51.7 ± 12.4 years) were enrolled in a prospective follow-up study. We examined serum creatinine, C-reactive protein, procalcitonin, fasting glucose and lipid parameters before, then 1 and 6 months after TX. High-density lipoprotein- (HDL)-associated paraoxonase-1 (PON1) paraoxonase and arylesterase activities were measured spectrophotometrically. Lipoprotein subfractions were determined by Lipoprint. NT-proCNP and oxidized low-density lipoprotein (oxLDL) levels were measured by ELISA. Mean NT-proCNP was 45.8 ± 21.9 pmol/L before renal transplantation and decreased markedly 1 month and 6 months after transplantation (5.3 ± 2.5 and 7.7 ± 4.9 pmol/L, respectively, P = 1 × 10−4). During the 6 months’ follow-up, PON1 arylesterase, paraoxonase and salt-stimulated paraoxonase activities improved. NT-proCNP positively correlated with procalcitonin and creatinine and negatively with GFR, LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C). There was a negative correlation between serum NT-proCNP and PON1 arylesterase activity. According to the multiple regression analysis, the best predicting variables of NT-proCNP were serum procalcitonin, creatinine and PON1 arylesterase activity. NT-proCNP might be a novel link between HDL dysfunction and impaired vascular function in ESRD, but not after kidney transplantation. Further studies in larger populations are needed to clarify the exact role of NT-proCNP in the risk prediction for cardiovascular comorbidities and complications in ESRD.
In end stage renal disease (ESRD) enhanced vascular inflammation characterized by increased high-sensitivity C-reactive protein (hsCRP) and procalcitonin levels induces the endothelial expression of amino-terminal C-type natriuretic peptide (NT-proCNP) and the formation of reactive oxygen species which modifies the structure and function of high-density lipoprotein (HDL); leading to impaired human paraoxonase-1 (PON1) arylesterase activity and increases oxidized low-density lipoprotein (oxLDL) level. Besides diminishing renal clearance and an increase in tubular reabsorption of NT-proCNP, increased renal expression of NT-proCNP as a response to renal tubular injury also contributes to the higher circulating NT-proCNP in ESRD. NT-proCNP is produced as a propeptide (preproCNP), which is then cleaved into the biologically active C-terminal hormone (CNP), a signal peptide and the amino-terminal fragment (NT-proCNP). Serum NT-proCNP and HDL3 subfraction showed significant negative correlation with PON1 arylesterase activity, which highlights the intimate interaction between vascular function and HDL-quality in ESRD.After renal transplantation, there is an increase in oxidative stress associated to ischemia reperfusion. Furthermore, administration of immunosuppressive agents may also contribute to increased oxidative stress resulting in increased level of oxLDL. After renal transplantation we simultaneously found decreased inflammatory markers including hsCRP and procalcitonin compared to pre-TX. PON1 arylesterase activity significantly increased after kidney transplantation. We found a significant and permanent decrease in NT-proCNP after transplantation, which can be explained by the improved renal function. Furthermore, beneficial effect of transplantation on inflammatory processes may also contribute to decreased NT-proCNP due to the decelerated production of CNP. However, correlation between arylesterase activity, procalcitonin and NT-proCNP cannot be detected after transplantation. Based on our results, in ESRD patients increased serum NT-proCNP closely correlates with renal function, procalcitonin, HDL subfraction distribution and HDL's antioxidant function characterized by PON1 activities. After kidney transplantation, there is a significant and permanent drop in serum NT-proCNP, which is predominantly caused by improved renal function and inflammatory status. Display omitted
•Serum NT-proCNP levels were measured in ESRD and renal transplanted patients.•Mean NT-proCNP was decreased markedly 1 month and 6 months after transplantation.•PON1 arylesterase and paraoxonase activities improved after transplantation.•There was a negative correlation between NT-proCNP and PON1 arylesterase activity.•NT-proCNP might be a novel link between HDL dysfunction and vascular function.
Objectives
Progranulin (PGRN) is a secreted growth factor that helps to regulate neuronal survival by blocking tumor necrosis factor-alpha (TNFα) receptors. The antioxidant alpha-lipoic acid (ALA) is ...used in diabetic neuropathy to improve nerve conduction and relieve neuropathic pain, but its effects on PGRN levels have not yet been elucidated.
Methods
In this prospective study, 54 patients with type 2 diabetes and peripheral neuropathy received 600 mg of ALA daily for 6 months. Twenty-four patients with diabetes without neuropathy were also included in the study. Serum PGRN and TNFα levels were determined using enzyme-linked immunosorbent assays. In addition, current perception threshold (CPT) testing was used to assess sensory neuropathy.
Results
After ALA treatment, serum PGRN levels were significantly increased and CPT values were significantly improved. Furthermore, there were significant positive correlations among TNFα, ICAM-1, and PGRN levels both before and after ALA treatment. A significant negative correlation was observed between the improvements in CPT and the PGRN levels. Furthermore, ICAM-1 levels were an independent predictor of PGRN levels.
Conclusions
Changes in serum PGRN levels indicate that ALA treatment may have beneficial effects on endothelial function and neuronal inflammation.
The prevalence of obesity has been increasing worldwide. Chemerin is a recently discovered adipokine secreted by the enlarged adipose tissue with diverse biological effects that are not well detailed ...yet. This study aimed to elucidate the potential role of chemerin in oxidative stress and inflammation that are characteristics for excess weight and may eventually lead to insulin resistance and atherosclerotic complications. We also analysed the associations between chemerin and classical adipokines, namely leptin and adiponectin. Therefore, we investigated non‐diabetic obese patients without manifest cardiovascular disease and compared their data to healthy lean individuals. Chemerin correlated positively with markers of oxidative stress and inflammation, while it showed a negative correlation with the measure of antioxidant status, characterized by the HDL‐linked paraoxonase‐1 enzyme. Chemerin also correlated positively with leptin and negatively with adiponectin respectively. In our study population, oxidized low‐density lipoprotein and high‐sensitivity C‐reactive protein were found to be the strongest predictors of chemerin level. We conclude that chemerin may contribute to chronic inflammation and increased oxidative stress in obese individuals, even in the absence of manifest insulin resistance.
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