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1.
Optimum lipid testing for diabetic patients to enhance clinical care.
Devaraj, S, Jialal, I
Diabetes & metabolic syndrome. 2021;(1):461-464
Abstract
BACKGROUND AND AIMS Dyslipidemia is a common problem in diabetic patients that predisposes to premature ASCVD. Dyslipidemia in Type 2 diabetes (T2DM) is very common and is characterized by hypertriglyceridemia (HTG) with decreased levels of high-density lipoprotein (HDL)-cholesterol. METHODS Recommendations for lipid testing in diabetics from the Canadian, European and American guidelines will be discussed in this mini-review. RESULTS It is crucial to obtain appropriate lipid testing in patients with TG > 2.3 mmol/L and or LDL-C< 1.8 mmol/L. We also discuss the utility of the different measures of calculated LDL-C and their pitfalls. CONCLUSION In conclusion, we propose obtaining a non-HDL-C (preferred) or direct -LDL-C or apo B level to manage diabetic patients with dyslipidemia and optimize care. Also in some patients with a strong FH of premature ASCVD and have few or no risk factors, Lp (a) can be assayed to optimize statin therapy.
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2.
ABCA1 and metabolic syndrome; a review of the ABCA1 role in HDL-VLDL production, insulin-glucose homeostasis, inflammation and obesity.
Babashamsi, MM, Koukhaloo, SZ, Halalkhor, S, Salimi, A, Babashamsi, M
Diabetes & metabolic syndrome. 2019;(2):1529-1534
Abstract
ATP-binding cassette transporter A1 (ABCA1) is an integral cell-membrane protein that mediates the rate-limiting step of high density lipoprotein (HDL) biogenesis and suppression of inflammation by triggering a number of signaling pathways via interacting with an apolipoprotein acceptor. The hepatic ABCA1 is involved in regulation of very low density lipoprotein (VLDL) production by affecting the apolipoprotein B trafficking and lipidation of VLDL particles. This protein is involved in protecting the function of pancreatic β-cells and insulin secretion by cholesterol homeostasis. Adipose tissue lipolysis is associated with ABCA1 activity. This transporter is involved in controlling obesity and insulin sensitivity by regulating triglyceride (TG) lipolysis and influencing on adiponectin, visfatin, leptin, and GLUT4 genes expression. The ABCA1 of skeletal muscle cells play a role in increasing the glucose uptake by enhancing the Akt phosphorylation and transferring GLUT4 to the plasma membrane. Abnormal status of ABCA1-regulated phenotypes is observed in metabolic syndrome. This syndrome is associated with the occurrence of many diseases. This review is a summary of the role of ABCA1 in HDL and VLDL production, homeostasis of insulin and glucose, suppression of inflammation and obesity controlling to provide a better insight into the association of this protein with metabolic syndrome.
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3.
Effects of Freeze-Dried Grape Powder on High-Density Lipoprotein Function in Adults with Metabolic Syndrome: A Randomized Controlled Pilot Study.
Millar, CL, Duclos, Q, Garcia, C, Norris, GH, Lemos, BS, DiMarco, DM, Fernandez, ML, Blesso, CN
Metabolic syndrome and related disorders. 2018;(9):464-469
Abstract
BACKGROUND High-density lipoprotein (HDL) particles are protective against atherosclerosis. However, HDL function is impaired in metabolic syndrome (MetS) due to low-grade inflammation and dyslipidemia. Foods containing polyphenols, such as grapes, may prevent HDL dysfunction via antioxidant or anti-inflammatory effects. We evaluated the effects of grape powder ingestion on measures of HDL function in adults with MetS. METHODS Twenty adults (age: 32-70 years; body mass index: 25.3-45.4 kg/m2) consumed either 60 grams/day of freeze-dried grape powder (GRAPE) or a placebo for 4 weeks, separated by a 3-week washout period, in a randomized, double-blind crossover study. The primary outcome was serum paraoxonase-1 (PON1) arylesterase activity, a measure of HDL antioxidant function. Secondary outcomes included PON1 lactonase activity, plasma lipids, metabolic markers, cholesterol efflux capacity, and other HDL functional markers. RESULTS After 4 weeks, GRAPE did not alter the serum PON1 activity or other markers of HDL function compared with placebo. Measures of HDL function were positively correlated with each other and inversely with measures of insulin resistance and inflammation. GRAPE intake led to a significant reduction in fasting plasma triglycerides compared with placebo (P = 0.032). No other significant effects of GRAPE were observed for other plasma lipids, anthropometrics, or metabolic measures. CONCLUSIONS Grape powder consumption did not impact HDL function in this cohort of adults with MetS. However, it was shown to improve fasting triglycerides, a risk factor for cardiovascular disease.
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4.
Weight Loss and Exercise Alter the High-Density Lipoprotein Lipidome and Improve High-Density Lipoprotein Functionality in Metabolic Syndrome.
Khan, AA, Mundra, PA, Straznicky, NE, Nestel, PJ, Wong, G, Tan, R, Huynh, K, Ng, TW, Mellett, NA, Weir, JM, et al
Arteriosclerosis, thrombosis, and vascular biology. 2018;(2):438-447
Abstract
OBJECTIVE High-density lipoprotein (HDL) lipid composition and function may better reflect cardiovascular risk than HDL cholesterol concentration. This study characterized the relationships between HDL composition, metabolism, and function in metabolic syndrome (MetS) patients and how changes in composition after weight loss (WL) and exercise treatments are related to function. APPROACH AND RESULTS Plasma samples from MetS patients (n=95) and healthy individuals (n=40) were used in this study. Subsets of the MetS group underwent 12 weeks of no treatment (n=17), WL (n=19), or WL plus exercise (WLEX; n=17). HDL was isolated using density-gradient ultracentrifugation. The HDL lipidome was analyzed by mass spectrometry, and particle size determined by nuclear magnetic resonance. Cholesteryl ester transfer protein activity and ex vivo HDL cholesterol efflux capacity (CEC) were assessed. The HDL lipidome in the MetS patients was substantially different from that in healthy individuals, mean particle size was smaller, and CEC was lower. Several HDL phospholipid and sphingolipid species were associated with HDL diameter and CEC. The HDL lipidome and particle size were modified toward the healthy individuals after WL and WLEX treatments, with greater effects observed in the latter group. Cholesteryl ester transfer protein activity was reduced after WL and WLEX, and CEC was improved after WLEX. CONCLUSIONS WLEX treatment in MetS patients normalizes the HDL lipidome and particle size profile and enhances CEC. HDL lipids associated with diminished CEC may represent novel biomarkers for early prediction of HDL dysfunction and disease risk and may represent potential therapeutic targets for future HDL therapies. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00163943.
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5.
High-Density Lipoprotein Reduction Differentially Modulates to Classical and Nonclassical Monocyte Subpopulations in Metabolic Syndrome Patients and in LPS-Stimulated Primary Human Monocytes In Vitro.
Grün, JL, Manjarrez-Reyna, AN, Gómez-Arauz, AY, Leon-Cabrera, S, Rückert, F, Fragoso, JM, Bueno-Hernández, N, Islas-Andrade, S, Meléndez-Mier, G, Escobedo, G
Journal of immunology research. 2018;:2737040
Abstract
The effect of metabolic syndrome on human monocyte subpopulations has not yet been studied. Our main goal was to examine monocyte subpopulations in metabolic syndrome patients, while also identifying the risk factors that could directly influence these cells. Eighty-six subjects were divided into metabolic syndrome patients and controls. Monocyte subpopulations were quantified by flow cytometry, and interleukin- (IL-) 1β secretion levels were measured by ELISA. Primary human monocytes were cultured in low or elevated concentrations of high-density lipoprotein (HDL) and stimulated with lipopolysaccharide (LPS). The nonclassical monocyte (NCM) percentage was significantly increased in metabolic syndrome patients as compared to controls, whereas classical monocytes (CM) were reduced. Among all metabolic syndrome risk factors, HDL reduction exhibited the most important correlation with monocyte subpopulations and then was studied in vitro. Low HDL concentration reduced the CM percentage, whereas it increased the NCM percentage and IL-1β secretion in LPS-treated monocytes. The LPS effect was abolished when monocytes were cultured in elevated HDL concentrations. Concurring with in vitro results, IL-1β serum values significantly increased in metabolic syndrome patients with low HDL levels as compared to metabolic syndrome patients without HDL reduction. Our data demonstrate that HDL directly modulates monocyte subpopulations in metabolic syndrome.
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6.
Apolipoprotein A-I exchange is impaired in metabolic syndrome patients asymptomatic for diabetes and cardiovascular disease.
Borja, MS, Hammerson, B, Tang, C, Savinova, OV, Shearer, GC, Oda, MN
PloS one. 2017;(8):e0182217
Abstract
OBJECTIVE We tested the hypothesis that HDL-apolipoprotein A-I exchange (HAE), a measure of high-density lipoprotein (HDL) function and a key step in reverse cholesterol transport (RCT), is impaired in metabolic syndrome (MetSyn) patients who are asymptomatic for diabetes and cardiovascular disease. We also compared HAE with cell-based cholesterol efflux capacity (CEC) to address previous reports that CEC is enhanced in MetSyn populations. METHODS HAE and ABCA1-specific CEC were measured as tests of HDL function in 60 MetSyn patients and 14 normolipidemic control subjects. Predictors of HAE and CEC were evaluated with multiple linear regression modeling using clinical markers of MetSyn and CVD risk. RESULTS HAE was significantly reduced in MetSyn patients (49.0 ± 10.9% vs. 61.2 ± 6.1%, P < 0.0001), as was ABCA1-specific CEC (10.1 ± 1.6% vs. 12.3 ± 2.0%, P < 0.002). Multiple linear regression analysis identified apoA-I concentration as a significant positive predictor of HAE, and MetSyn patients had significantly lower HAE per mg/dL of apoA-I (P = 0.004). MetSyn status was a negative predictor of CEC, but triglyceride (TG) was a positive predictor of CEC, with MetSyn patients having higher CEC per mg/dL of TG, but lower overall CEC compared to controls. CONCLUSIONS MetSyn patients have impaired HAE that contributes to reduced capacity for ABCA1-mediated CEC. MetSyn status is inversely correlated with CEC but positively correlated with TG, which explains the contradictory results from earlier MetSyn studies focused on CEC. HAE and CEC are inhibited in MetSyn patients over a broad range of absolute apoA-I and HDL particle levels, supporting the observation that this patient population bears significant residual cardiovascular disease risk.
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7.
HDL-sphingomyelin reduction after weight loss by an energy-restricted diet is associated with the improvement of lipid profile, blood pressure, and decrease of insulin resistance in overweight/obese patients.
Martínez-Ramírez, M, Madero, M, Vargas-Alarcón, G, Vargas-Barrón, J, Fragoso, JM, Rodríguez-Pérez, JM, Martínez-Sánchez, C, González-Pacheco, H, Bautista-Pérez, R, Carreón-Torres, E, et al
Clinica chimica acta; international journal of clinical chemistry. 2016;:77-81
Abstract
BACKGROUND Sphingomyelin (SM) diminishes the fluidity of the surface monolayer of high-density lipoproteins (HDL), affecting their intravascular metabolism and antiatherogenic properties. Since overweight is associated with an altered HDL structure, weight loss may result in changes in HDL subclasses, particularly in their SM content. Therefore, we determined the plasma SM concentrations associated to both total HDL and HDL subclasses after weight loss in obese patients. METHODS Fifty overweight patients, 40 women and 10 men, aged 38.6±6.4 y, were given an energy-restricted diet according to their sex, age, and height. No physical activity was prescribed. Plasma SM concentrations of HDL subclasses were determined by a gel surface method developed for this study. Cholesterol of HDL subclasses was also determined by enzymatic methods performed on a gel surface. RESULTS Mean weight lost was 3.5±0.4 kg after 6 weeks of dietary intervention. As expected, insulin resistance and blood pressure decreased whereas lipid profile improved, except for HDL-cholesterol. SM in plasma and in all HDL subclasses significantly decreased after intervention. The magnitude of HDL-SM reduction was statistically associated with the amelioration of the components of the metabolic syndrome; the reduction of BMI explained the decrement of HDL-SM in a multivariate analysis. CONCLUSION HDL-SM decreased after weight loss by an energy-restricted diet. Further, the association of this decrement with the improvement of blood pressure, lipid profile and the decrease of insulin resistance, was statistically significant; all HDL subclasses were similarly affected. Whether a reduction in HDL-SM contributes to the cardiovascular benefits of weight loss remains to be elucidated.
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8.
HDL abnormalities in nephrotic syndrome and chronic kidney disease.
Vaziri, ND
Nature reviews. Nephrology. 2016;(1):37-47
Abstract
Normal HDL activity confers cardiovascular and overall protection by mediating reverse cholesterol transport and through its potent anti-inflammatory, antioxidant, and antithrombotic functions. Serum lipid profile, as well as various aspects of HDL metabolism, structure, and function can be profoundly altered in patients with nephrotic range proteinuria or chronic kidney disease (CKD). These abnormalities can, in turn, contribute to the progression of cardiovascular complications and various other comorbidities, such as foam cell formation, atherosclerosis, and/or glomerulosclerosis, in affected patients. The presence and severity of proteinuria and renal insufficiency, as well as dietary and drug regimens, pre-existing genetic disorders of lipid metabolism, and renal replacement therapies (including haemodialysis, peritoneal dialysis, and renal transplantation) determine the natural history of lipid disorders in patients with kidney disease. Despite the adverse effects associated with dysregulated reverse cholesterol transport and advances in our understanding of the underlying mechanisms, safe and effective therapeutic interventions are currently lacking. This Review provides an overview of HDL metabolism under normal conditions, and discusses the features, mechanisms, and consequences of HDL abnormalities in patients with nephrotic syndrome or advanced CKD.
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9.
Effect of an isoenergetic traditional Mediterranean diet on the high-density lipoprotein proteome in men with the metabolic syndrome.
Richard, C, Couture, P, Desroches, S, Nehmé, B, Bourassa, S, Droit, A, Lamarche, B
Journal of nutrigenetics and nutrigenomics. 2014;(1):48-60
Abstract
BACKGROUND/AIMS: The objective of this preliminary study was to examine the impact of the Mediterranean diet (MedDiet) on the high-density lipoprotein (HDL) proteome in men with the metabolic syndrome (MetS). METHODS Twenty-six men with the MetS first consumed a standardized baseline North American isoenergetic control diet (5 weeks) and then consumed an isoenergetic MedDiet (5 weeks), both in full feeding condition. The HDL fraction was isolated by ultracentrifugation at the end of each diet and the HDL proteome assessed by isobaric tags for relative and absolute quantitation and mass spectrometry. RESULTS Of all proteins identified within HDL, only 3 showed significant changes in relative abundance after the MedDiet versus the control diet, including a reduction in inflammation-related inter-α-trypsin inhibitor heavy chain H4 (fold change: 0.62) and hemoglobin subunits α (fold change: 0.40) and β (fold change: 0.46). Other HDL-bound proteins associated with functions related to lipid metabolism/cholesterol homeostasis, oxidation, coagulation, complement activation and immunity were unchanged after consumption of the MedDiet for 5 weeks. CONCLUSIONS Changes in the HDL proteome may explain, at least partly, the well-known anti-inflammatory effect ascribed to the MedDiet. Otherwise, short-term consumption of the MedDiet seems to have little impact on other features of the HDL proteome in men with the MetS.
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10.
Genes associated with low serum high-density lipoprotein cholesterol.
Ahmadzadeh, A, Azizi, F
Archives of Iranian medicine. 2014;(6):444-50
Abstract
Atherosclerosis is the main cause of death in the world through causing ischemic heart disease (IHD). Altered serum lipid level is the most important risk factor for coronary artery disease (CAD). Many studies reveal a strong inverse association between low levels of high density lipoprotein cholesterol (HDL-C) and increased risk of IHD. On the other hand, plasma levels of HDL-C has a strong hereditary basis. This review focuses on recent data about genetic defects that reduce the level of HDL-C. In order to investigate possible genes linked to low HDL-C disorder, we reviewed previous studies; we searched current medical literature from September 1990 through January 2013 for the genetics causes of low HDL-C levels. Genetic defects in ATP binding cassette protein (ABCA1), apolipoprotein (APO) A1, lecithin cholesteryl acyl transferase, Lipoprotein lipase (LPL), and angiopoietin-like 3 proteins (ANGPTL3) associated with low HDL-C. Other potentially important candidates involved in low HDL-C syndromes are metabolic disorders including sphingomyelin phosphodiesterase 1 and glucocerebrosidase. Also Molecular variations in many genes such as ABCAI and APOAI, TRIB1 and Apo E, lipoprotein lipase (LPL), WW domain-containing oxidoreductase (WWOX), Hepatic lipase (HL), lecithin cholesteryl acyl transferase and some linkage analysis have been associated with reduced HDL-Status. Low HDL-C syndrome has a strong genetic basis and is correlated with an increased risk of CAD.