Lower HDL-cholesterol Concentrations Research Articles

Appraising associations between signature lipidomic biomarkers and digestive system cancer risk: novel evidences from a prospective cohort study of UK Biobank and Mendelian randomization analyses

BackgroundThe roles of serum lipids on digestive system cancer (DSC) risk were still inconclusive. In this study, we systematically assessed indicative effects of signature lipidomic biomarkers (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)) on DSC (oesophagus, stomach, colorectal, liver, gallbladder, and pancreas cancers) risk.MethodsHDL-C, LDL-C, and TG concentration measurements were respectively analyzed with enzyme immunoinhibition, enzymatic selective protection, and GPO-POD methods in AU5800 supplied from Beckman Coulter. The diagnoses of DSCs were coded using International Classification of Diseases, Tenth Revision (ICD-10) codes updated until October 2022 in the UK Biobank (UKB). In this study, we assessed phenotypic association patterns between signature lipidomic biomarkers and DSC risk using restricted cubic splines (RCSs) in multivariable-adjusted Cox proportional hazards regression models. Moreover, linear and nonlinear causal association patterns of signature lipidomic biomarkers with DSC risk were determined by linear and nonlinear Mendelian randomization (MR) analyses.ResultsA median follow-up time of 11.8 years was recorded for 319,568 participants including 6916 DSC cases. A suggestive independent nonlinear phenotypic association was observed between LDL-C concentration and stomach cancer risk (Pnonlinearity < 0.05, Poverall < 0.05). Meanwhile, a remarkable independent linear negative phenotypic association was demonstrated between HDL-C concentration and stomach cancer risk (Pnonlinearity > 0.05, Poverall < 0.008 (0.05/6 outcomes, Bonferroni-adjusted P)), and suggestive independent linear positive associations were observed between HDL-C concentration and colorectal cancer risk, and between TG concentration and gallbladder cancer risk (Pnonlinearity > 0.05, Poverall < 0.05). Furthermore, based on nonlinear and linear MR-based evidences, we observed an suggestive independent negative causal association (hazard ratio (HR) per 1 mmol/L increase: 0.340 (0.137-0.843), P = 0.020) between LDL-C and stomach cancer risk without a nonlinear pattern (Quadratic P = 0.901, Cochran Q P = 0.434). Meanwhile, subgroup and stratified MR analyses both supported the category of LDL-C ≥ 4.1 mmol/L was suggestively protective against stomach cancer risk, especially among female participants (HR: 0.789 (0.637-0.977), P = 0.030) and participants aged 60 years or older (HR: 0.786 (0.638-0.969), P = 0.024), and the category of TG ≥ 2.2 mmol/L concluded to be a suggestive risk factor for gallbladder cancer risk in male participants (HR: 1.447 (1.020-2.052), P = 0.038) and participants aged 60 years or older (HR: 1.264 (1.003-1.593), P = 0.047).ConclusionsOur findings confirmed indicative roles of signature lipidomic biomarkers on DSC risk, notably detecting suggestive evidences for a protective effect of high LDL-C concentration on stomach cancer risk, and a detrimental effect of high TG concentration on gallbladder cancer risk among given participants.

ABCA1 variant rs9282541 is associated with metabolic syndrome in Maya children.

Metabolic syndrome (MetS) is a metabolic disorder encompassing risk factors for cardiovascular disease and type 2 diabetes (T2D). In Mexico, the MetS is a national health problem in adults and children. Environmental and genetic factors condition the MetS. However, studies to elucidate the contribution of genetic factors to MetS in Mexico are scarce. A recent study showed that variant rs9282541 (A-allele) in ATP-binding cassette transporter A1 (ABCA1) was associated with T2D in the Maya population in addition to low levels of high-density lipoprotein cholesterol (HDL-C). Thus, this study aimed to determine whether the genetic variant of ABCA1 A-allele (rs9282541, NM_005502.4:c.688C>T, NP_005493.2:p.Arg230Cys) is associated with MetS and its components in Mexican Maya children. The study was conducted in 508 children aged 9-13 from the Yucatán Peninsula. MetS was identified according to the de Ferranti criteria. Genotyping was performed using TaqMan assay by real-time PCR. Evaluation of genetic ancestry group was included. The frequency of MetS and overweight-obesity was 45.9% and 41.6%, respectively. The genetic variant rs9282541 was associated with low HDL-C and high glucose concentrations. Remarkably, for the first time, this study showed the association of ABCA1 rs9282541 with MetS in Maya children with an OR of 3.076 (95% CI=1.16-8.13 p=0.023). Finally, this study reveals a high prevalence of MetS and suggests that variant rs9282541 of the ABCA1 gene plays an important role in the developing risk of MetS in Maya children.

Lipids, lipoproteins, and apolipoproteins during the first year of life: a prospective cohort study

Abstract Background/Introduction Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally, and treatment of well-established lifestyle risk factors are cornerstones in CVD prevention. An atherogenic lipid profile with high concentrations of low-density lipoprotein (LDL) cholesterol and other apolipoprotein B containing lipoproteins is a driving force in the pathogenesis of atherosclerotic CVD (ASCVD). The lifelong atherosclerotic process is proportional to concentrations of apolipoprotein B-containing lipoproteins, hence risk of developing ASCVD is cumulative over time. The higher the baseline concentrations, the sooner the threshold for increased risk of ASCVD will be reached. It is therefore crucial to implement changes as early as possible and prevent risk factors in occurring – so-called primordial prevention. Childhood has been described as a "window of opportunity" for preventing risk factors in occurring and thus avoiding ASCVD. Whether concentrations of atherogenic lipoproteins at birth can predict future concentrations in early childhood and thus may indicate increased risk of dyslipidemia later in life remains unknown. Purpose The aim of the present study was to investigate atherogenic lipid traits during the first year of life, to identify influential factors for lipid concentrations, and to determine whether concentrations at birth can predict future lipid concentrations in early childhood. Methods For this purpose, we used the Copenhagen Baby Heart Study comprising more than 13,000 umbilical cord blood samples and parallel venous blood samples from children and parents at birth (n=444), at two months (n=363), and at 14-16 months (n=158). Lipid traits were determined in all samples. Results Concentrations of low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B increased during the first year of life. Girls had higher concentrations at birth and at two months compared with boys. Children born preterm had higher cord blood concentrations than children born at term. A linear mixed model showed that high concentrations of LDL cholesterol, non-HDL cholesterol and apolipoprotein B at birth predicted high concentrations at two months and at 14-16 months. Multivariable adjusted odds ratios (95% CI) for having high concentrations at two months when children had high concentrations at birth were 1.95 (1.01-3.79) for LDL cholesterol, 1.36 (0.69-2.67) for non-HDL cholesterol and 1.90 (1.02-3.53) for apolipoprotein B. Conclusion The lipid profile change during the first year of life and sex and gestational age influence concentrations. Children with high concentrations of LDL cholesterol, non-HDL cholesterol and apolipoprotein B at birth had higher levels at two and at 14-16 months. Concentrations at birth may thus be used to identify children at risk of dyslipidemia in later life.

Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium: a randomised controlled trial

Aims/hypothesisHypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown.MethodsUsing a randomised, double-blind (both participants and investigators were blinded to the participants’ treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age ≥18 years, BMI 18–40 kg/m2, HbA1c <100 mmol/mol [11.3%], serum magnesium ≤0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic–euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up.ResultsWe recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m2, HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg−1 min−1, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms.Conclusions/interpretationDespite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels.Trial registrationEudraCT number 2021-001243-27.FundingThis study was supported by a grant from the Dutch Diabetes Research Foundation (2017–81–014).Graphical

Prevalence of the metabolic syndrome by household food insecurity status in the United States adolescent population, 2001–2020: a cross-sectional study

BackgroundHousehold food insecurity (FI) is a modifiable social determinant of health linked to chronic health outcomes. Little is known, however, about the prevalence of metabolic syndrome (MetS) in pediatric population-based studies by household FI status. ObjectivesThe objective of the study was to estimate the prevalence of the MetS by household FI status over the past 2 decades. MethodsThis cross-sectional study used data from the 2001–2020 National Health and Nutrition Examination Survey (NHANES). Participants were nonpregnant adolescents ages 12– 18 y in United States. The prevalence of MetS [elevated waist circumference and >2 of the following risk factors: elevated blood pressure, and fasting glucose, triglyceride, and/or low high-density lipoprotein (HDL) cholesterol concentrations] by FI status was evaluated using chi-square and logistic regression analyses. ResultsThe estimated prevalence of MetS was 2.66% [95% confidence interval (CI): 2.28%, 3.09%] in the final analytical sample (unweighted N = 12,932). A total of 3.39% (95% CI: 2.53%, 4.53%) of adolescents from FI households had MetS compared to 2.48% (95% CI: 2.11%, 2.9%) among adolescents with no household FI. Hispanic adolescents had the highest prevalence of MetS (3.73%, 95% CI: 3.05, 4.56) compared with adolescents who identified as non-Hispanic White (2.78%, 95% CI: 2.25, 3.43), non-Hispanic Black (1.58%, 95% CI: 1.19, 2.10). Adolescents with household FI (23.20%) were more likely to have MetS [odds ratio (OR): 1.38; 95% CI: 1.02, 1.88; I=0.039) compared with adolescents with no household FI, but in fully adjusted models this was not significant (OR: 1.13; 95% CI: 0.75, 1.72). ConclusionsUsing the most current NHANES data, the estimated prevalence of MetS in adolescents in United States was slightly higher among those from FI households. However, after adjusting for potential confounders, the relationship between household FI and MetS was nonsignificant, highlighting the complexity of factors contributing to MetS in this population. Hispanic adolescents share a disproportionate burden of MetS compared with their non-Hispanic counterparts.

SYNERGISTIC EFFECT OF FRUITS EXTRACTS OF Balanites aeqyptiaca AND Adansonia digitata ON LIPIDERMIC PARAMETERS OF DIABETICS ALBINO RAT

Lipidemia is a significant risk factor for cardiovascular disease, particularly in people with diabetes mellitus. High plasma triglyceride concentration, low HDL cholesterol concentration, and elevated concentration of tiny dense LDL cholesterol particles are some of its distinguishing features. Fruits from Balanites aeqyptiaca and Adansonia digitata have the ability to decrease blood pressure. Therefore, the purpose of this study is to examine the combined effects of the two fruits on the lipidemia of alloxan-induced albino rats. Utilizing the glucose dehydrogenase method, glucometer accu-check was used for the evaluation of blood glucose levels. Investigations were also conducted on alloxan-induced diabetic albino rats to measure total cholesterol, triglycerides, high density lipoprotein (HDL), and low density lipoprotein (LDL). According to the results, B. aegyptiaca and A. digitata fruit extracts significantly reduced the lipid profiles of the treated groups when used at concentrations of 80:20, 160:40, and 240:60 mg/Kg body weight, respectively. While the lipid profiles were significantly reduced in groups that received treatment at dosages of 100, 200, and 300 mg/kg body weight. However, the groups treated with the highest doses of the extracts demonstrated the most significant effects on the levels of triglycerides (47mg/dl), HDL (79mg/dl), and LDL (40mg/dl). The fruits have shown cumulative effects on their potential to lower the lipid profile of diabetic rats, validating their folkloric usage in the management of cardiovascular illnesses.

Identification of the specific molecular and functional signatures of pre-beta-HDL: relevance to cardiovascular disease.

While low concentrations of high-density lipoprotein-cholesterol (HDL-C) are widely accepted as an independent cardiovascular risk factor, HDL-C-rising therapies largely failed, suggesting the importance of both HDL functions and individual subspecies. Indeed HDL particles are highly heterogeneous, with small, dense pre-beta-HDLs being considered highly biologically active but remaining poorly studied, largely reflecting difficulties for their purification. We developed an original experimental approach allowing the isolation of sufficient amounts of human pre-beta-HDLs and revealing the specificity of their proteomic and lipidomic profiles and biological activities. Pre-beta-HDLs were enriched in highly poly-unsaturated species of phosphatidic acid and phosphatidylserine, and in an unexpectedly high number of proteins implicated in the inflammatory response, including serum paraoxonase/arylesterase-1, vitronectin and clusterin, as well as in complement regulation and immunity, including haptoglobin-related protein, complement proteins and those of the immunoglobulin class. Interestingly, amongst proteins associated with lipid metabolism, phospholipid transfer protein, cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase were strongly enriched in, or restricted to, pre-beta-HDL. Furthermore, pre-beta-HDL potently mediated cellular cholesterol efflux and displayed strong anti-inflammatory activities. A correlational network analysis between lipidome, proteome and biological activities highlighted 15 individual lipid and protein components of pre-beta-HDL relevant to cardiovascular disease, which may constitute novel diagnostic targets in a pathological context of altered lipoprotein metabolism.

C3H/HeNSlc mouse with low phospholipid transfer protein expression showed dyslipidemia

High serum levels of triglycerides (TG) and low levels of high-density lipoprotein cholesterol (HDL-C) increase the risk of coronary heart disease in humans. Herein, we first reported that the C3H/HeNSlc (C3H-S) mouse, a C3H/HeN-derived substrain, is a novel model for dyslipidemia. C3H-S showed hypertriglyceridemia and low total cholesterol (TC), HDL-C, and phospholipid (PL) concentrations. To identify the gene locus causing dyslipidemia in C3H-S, we performed genetic analysis. In F2 intercrosses between C3H-S mice and strains with normal serum lipids, the locus associated with serum lipids was identified as 163–168 Mb on chromosome 2. The phospholipid transfer protein (Pltp) gene was a candidate gene within this locus. Pltp expression and serum PLTP activity were markedly lower in C3H-S mice. Pltp expression was negatively correlated with serum TG and positively correlated with serum TC and HDL-C in F2 mice. Genome sequencing analysis revealed that an endogenous retrovirus (ERV) sequence called intracisternal A particle was inserted into intron 12 of Pltp in C3H-S. These results suggest that ERV insertion within Pltp causes aberrant splicing, leading to reduced Pltp expression in C3H-S. This study demonstrated the contribution of C3H-S to our understanding of the relationship between TG, TC, and PL metabolism via PLTP.

FTO Gene Polymorphisms and Their Roles in Acromegaly.

The major causes of both morbidity and mortality in patients with acromegaly are cardiovascular diseases (CVDs). The polymorphisms of the fat mass and obesity-associated gene (FTO) are associated with obesity, as well as with an increased risk of CVDs. The aim of the study was to determine the relationship of risk alleles of four FTO gene polymorphisms with selected parameters of lipid and glucose metabolism as well as with IGF-1 and GH levels in the group of patients with acromegaly compared to the control group. The study group consisted of 104 patients with acromegaly and 64 healthy subjects constituting the control group. In the whole acromegaly group, the data reveal that the homozygous for risk allele carriers (rs1421085, rs9930506, rs9939609) as well as carriers of only one risk allele have lower IGF-1 concentrations. In the well-controlled acromegaly group, the homozygous for three risk allele carriers of FTO gene polymorphisms have lower HDL cholesterol concentration (rs1121980, rs1421085, rs993609). In the cured acromegaly group, homozygous risk allele carriers rs9930506 tend to have higher levels of total cholesterol and LDL cholesterol. These associations are not observed in the control group. Conclusion: there is an association between FTO gene polymorphisms and the metabolism of lipids, suggesting that the FTO gene may be associated with higher CVD risk in patients with acromegaly. In addition, there is an association between FTO gene polymorphisms and IGF-1, implying that FTO gene may influence/modify IGF-1 synthesis. Further investigation on a larger scale is required to provide more precise evidence.

Atherogenic dyslipidaemia in type 2 diabetes mellitus: The PREDISAT study.

Extremely variable prevalence rates of atherogenic dyslipidaemia (AD) in type 2 diabetes (T2DM) subjects have been reported. The primary aim was to assess AD prevalence in Spanish T2DM subjects. Secondary objectives were to evaluate the differential clinical characteristics between T2DM subjects with and without AD, to describe lipid profile evolution and use of lipid-lowering treatment in clinical practice by the Spanish Lipid Units. Data was obtained from the National Registry of Dyslipidaemias of the Spanish Atherosclerosis Society, from a multicentric sub-study focused on AD prevalence in T2DM subjects (PREDISAT study). The inclusion criteria were subjects diagnosed of T2DM with age ≥18 years old. A total of 385 T2DM subjects with a mean age of 61 years and 246 (64%) men were included. The mean follow-up was 22 ± 7.4 months. At baseline, 41.3% of the T2DM subjects presented AD, this percentage decreasing to 34.8% with therapeutic intervention. AD prevalence varied in different age groups and appeared to be more prevalent in younger T2DM subjects. Those with AD had a more atherogenic lipid profile at baseline, with higher total cholesterol, triglyceride and non-(high-density lipoprotein) HDL cholesterol levels at baseline, together with lower HDL cholesterol concentrations, without achieving lipid subfraction goals during follow-up. Although almost 90% of the AD subjects were under lipid-lowering treatment, most were receiving only one drug, being statins the most used treatmentA high AD prevalence in T2DM subjects was observed, being age a determinant factor, with a modest decline during follow-up. Although almost 90% of the AD subjects were under lipid-lowering drugs, most were only receiving monotherapy with statins.

Fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease (25-30% of the global adult general population) with no approved treatment to-date, although its treatment is attractive for the researchers and the pharmaceutical industry. The cessation of ovarian function (natural or iatrogenic menopause, premature ovarian insufficiency) is associated with increased abdominal adipose tissue and changes in carbohydrate and lipid metabolism. These changes lead to a dysmetabolic milieu, characterized by unfavorable lipid profile and the development of NAFLD, which may contribute to the increase in cardiovascular risk observed after menopause. Not only the prevalence of NAFLD seems to be higher in postmenopausal compared with premenopausal women, but also the rates of advanced types of the disease, i.e., nonalcoholic steatohepatitis and hepatic fibrosis, the latter regarded as the main histological prognostic factor of advanced liver disease and a difficult-to-reverse target. These observations may render menopausal hormone therapy (MHT) an appealing way to retard or even restore NAFLD after menopause. Although there are some experimental data favoring this consideration, there are only a few interventional clinical studies evaluating the effect of MHT on NAFLD, which have provided conflicting results. Some of them showed encouraging effects of MHT on liver function tests and/or lower rates of NAFLD in women receiving as compared with those not receiving MHT. However, other studies showed that MHT may adversely affect NAFLD. Regarding the route of administration of MHT, there are currently not comparative data between per os and transdermal use on NAFLD. Until waiting for the publication of relevant studies, based on the favorable effect of transdermal MHT on triglyceride concentrations and the fact that high triglyceride and low high-density lipoprotein-cholesterol concentrations are associated with the severity of NAFLD, the use of transdermal MHT may be preferred in women with NAFLD after the cessation of ovarian function. Of course, MHT could not be recommended as standard treatment of NAFLD in women, because MHT may be used for a certain time frame in a woman’s life. However, given that NAFLD seems to be common after the pause of ovarian function, any potential effect of MHT on NAFLD may be considered before treatment initiation and during the follow-up of these women.

HDL and chronic kidney disease

Low HDL-cholesterol (HDL-C) concentrations are a typical trait of the dyslipidemia associated with chronic kidney disease (CKD). In this condition, plasma HDLs are characterized by alterations in structure and function, and these particles can lose their atheroprotective functions, e.g., the ability to promote cholesterol efflux from peripheral cells, anti-oxidant and anti-inflammatory proprieties and they can even become dysfunctional, i.e., exactly damaging. The reduction in plasma HDL-C levels appears to be the only lipid alteration clearly linked to the progression of renal disease in CKD patients. The association between the HDL system and CKD development and progression is also supported by the presence of genetic kidney alterations linked to HDL metabolism, including mutations in the APOA1, APOE, APOL and LCAT genes. Among these, renal disease associated with LCAT deficiency is well characterized and lipid abnormalities detected in LCAT deficiency carriers mirror the ones observed in CKD patients, being present also in acquired LCAT deficiency. This review summarizes the major alterations in HDL structure and function in CKD and how genetic alterations in HDL metabolism can be linked to kidney dysfunction. Finally, the possibility of targeting the HDL system as possible strategy to slow CKD progression is reviewed.

Effects of the Ketogenic Diet on Metabolic Syndrome

The global prevalence of obesity and metabolic syndrome and its pathophysiologic sequela are currently approaching epidemic proportions, with unacceptable levels in much of Westernized and economically developed society. The clinical stigmata of metabolic syndrome typically include the comorbidities of obesity, hypertension, non-insulin dependent diabetes, and hyperlipidemia with decreased plasma high density lipoprotein concentrations. In addition, a common finding of hyperinsulinemia and insulin resistance typical of high carbohydrate diets often accompanies the syndrome. The incorporation of the insulin sparing ketogenic diet as a dietary strategy for the treatment of metabolic syndrome may bring about improvements in insulin action and substrate utilization in peripheral tissues with at least a partial if not significant resolution of the syndrome. Thus, the ketogenic diet in addition to adaptations toward a healthy lifestyle and pharmacologic therapies have been explored as potential mechanisms to resolve the pathophysiologic sequela of obesity and metabolic syndrome and their impact on the delivery of healthcare. Metabolic syndrome (MetS) is a condition defined as a clustering of risk factors that is strongly associated with obesity, heart disease, and diabetes [22]. It has recently been estimated that the global prevalence of MetS has reached epidemic levels including the U.S.A., where it has been estimated that 20% to 25% of the adult global population meets the diagnostic criterion for MetS [3], which may be established when at least three of the five primary risk factors are present. The risk factors include a large waistline (abdominal or visceral obesity), high plasma triglyceride levels, low plasma HDL cholesterol concentrations, elevated blood pressure, and fasting hyperglycemia. The standard and most effective treatments for MetS to date have been incorporation of lifestyle changes, with dietary interventions being one of the major effective lifestyle modifications utilized to treat both obesity and MetS [14];[41]. The Ketogenic Diet (KD) is one dietary intervention that may have the potential to improve MetS risk factors. Historically, one of the primary uses of the KD has been to treat epilepsy, however, there is substantial evidence that it may also help to improve other conditions and illnesses, including obesity and MetS [30]; [48]; [35]. Despite this potential, certain dietary misconceptions may have prevented or slowed further research on the KD applications to weight control and use of the KD, particularly the emergence of the national dietary guidelines that have now promoted a low-fat, high-carbohydrate diet for several decades [18]; [51]; [52]. The purpose of this paper is to conduct a review of the literature regarding MetS, the KD, and the implications of the KD as a treatment for obesity and MetS. Existing research is systematically reviewed regarding the KD’s potential to address MetS and MetS risk factors. The results of the review indicate the validity of the diet and the need for further research on the KD and its potential to address the benefits, potential risks and clinical efficacy of the KD on reducing the pathophysiologic sequalae of obesity and MetS. MetS = Metabolic Syndrome, KD = ketogenic diet, KB = ketone bodies, including metabolic remnants acetoacetate (AcAc),3-beta-hydroxybutyrate (3HB), and acetone, PSMF = Protein Sparing Modified Fast, HDL, HDL-C= plasma high density cholesterol lipoprotein, LDL, LDL-C = low density cholesterol lipoprotein, TG, TRIG = plasma triglycerides, CRP = C-reactive protein, GLUT4 = Glucose Transporter 4, and insulin-linked cellular entity, ATP = Adenosine tri-phosphate, a high energy phosphate, CCK = cholecystokinin, CR = calorie restricted diet, LFD = low fat diet, LCKD = low calorie ketogenic diet, BP = blood pressure; SBP = systolic blood pressure; DBP = diastolic blood pressure, A(1c) = glycosylated hemoglobin fraction, NHLBI = National Heart, Lung and Blood Institute of the National Institutes of Health

Replacement of dietary saturated with unsaturated fatty acids is associated with beneficial effects on lipidome metabolites: a secondary analysis of a randomized trial

BackgroundThe effects of replacing dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) and/or polyunsaturated fatty acids (PUFAs) on the plasma lipidome in relation to the cardiometabolic disease (CMD) risk is poorly understood. ObjectivesWe aimed to assess the impact of substituting dietary SFAs with unsaturated fatty acids (UFAs) on the plasma lipidome and examine the relationship between lipid metabolites modulated by diet and CMD risk. MethodsPlasma fatty acid (FA) concentrations among 16 lipid classes (within-class FAs) were measured in a subgroup from the Dietary Intervention and VAScular function (DIVAS) parallel randomized controlled trial (n = 113/195), which consisted of three 16-wk diets enriched in SFAs (target SFA:MUFA:n-6PUFA ratio = 17:11:4% total energy [TE]), MUFAs (9:19:4% TE), or a MUFA/PUFA mixture (9:13:10% TE). Similar lipidomics analyses were conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study (specific case/cohorts: n = 775/1886 for type 2 diabetes [T2D], n = 551/1671 for cardiovascular disease [CVD]). Multiple linear regression and multivariable Cox models identified within-class FAs sensitive to replacement of dietary SFA with UFA in DIVAS and their association with CMD risk in EPIC-Potsdam. Elastic-net regression models identified within-class FAs associated with changes in CMD risk markers post–DIVAS interventions. ResultsDIVAS high-UFA interventions reduced plasma within-class FAs associated with a higher CVD risk in EPIC-Potsdam, especially SFA-containing glycerolipids and sphingolipids (e.g., diacylglycerol (20:0) z-score = −1.08; SE = 0.17; P value < 10−8), whereas they increased those inversely associated with CVD risk. The results on T2D were less clear. Specific sphingolipids and phospholipids were associated with changes in markers of endothelial function and ambulatory blood pressure, whereas higher low-density lipoprotein cholesterol concentrations were characterized by higher plasma glycerolipids containing lauric and stearic acids. ConclusionsThese results suggest a mediating role of plasma lipid metabolites in the association between dietary fat and CMD risk. Future research combining interventional and observational findings will further our understanding of the role of dietary fat in CMD etiology.This trial was registered in ClinicalTrials.gov as NCT01478958.

The Association between the Atherogenic Index of Plasma and Cardiometabolic Risk Factors: A Review.

Metabolic syndrome (MetS) is a condition caused by a combination of cardiometabolic risk factors (CMR). MetS leads to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), both of which place a burden on not only the patients but also the healthcare system. Diagnostic criteria for MetS vary, and there is no universal tool to detect it. Recently, many studies have found positive associations between the atherogenic index of plasma (AIP) and some CMR factors. Therefore, a comprehensive review was needed to recapitulate these studies and qualitatively estimate the likelihood of AIP being associated with CMR. We aimed to review and summarise observational data on AIP and CMR factors and verify their association. A review of observational studies was conducted by searching "atherogenic index of plasma" in PubMed, One Search, and the Cochrane library. A total of 2068 articles were screened, and 32 were included after excluding paediatric, non-human and interventional studies, and those carried out on cohorts with conditions unrelated to MetS or on lipid-lowering medication. The Newcastle-Ottawa scale was used to assess their quality. Most studies that reported high waist circumference (WC), triglycerides (TG), insulin resistance (IR) and low high-density lipoprotein cholesterol (HDL-C) concentration, also reported high AIP. Few studies investigated blood pressure (BP) and some discrepancies existed between their results. AIP may be associated with WC, TG, IR, and HDL-C. It is unclear if AIP is associated with BP. The current study's results should be used to inform futureward a meta-analysis to be seen quantitatively. It is also recommended that more cohort studies stratified by gender and ethnicity be performed to ascertain if AIP can predict MetS before it manifests.

Dietary polyphenols, metabolic syndrome and cardiometabolic risk factors: An observational study based on the DCH-NG subcohort

Background and aimsPolyphenol-rich foods have beneficial properties that may lower cardiometabolic risk. We aimed to prospectively investigate the relationship between intakes of dietary polyphenols, and metabolic syndrome (MetS) and its components, in 676 Danish residents from the MAX study, a subcohort of the Danish Diet, Cancer and Health–Next Generations (DCH-NG) cohort. Methods and resultsDietary data were collected using web-based 24-h dietary recalls over one year (at baseline, and at 6 and 12 months). The Phenol-Explorer database was used to estimate dietary polyphenol intake. Clinical variables were also collected at the same time point. Generalized linear mixed models were used to investigate relationships between polyphenol intake and MetS. Participants had a mean age of 43.9y, a mean total polyphenol intake of 1368 mg/day, and 75 (11.6%) had MetS at baseline. Compared to individuals with MetS in Q1 and after adjusting for age, sex, lifestyle and dietary confounders, those in Q4 – for total polyphenols, flavonoids and phenolic acids–had a 50% [OR (95% CI): 0.50 (0.27, 0.91)], 51% [0.49 (0.26, 0.91)] and 45% [0.55 (0.30, 1.00)] lower odds of MetS, respectively. Higher total polyphenols, flavonoids and phenolic acids intakes as continuous variable were associated with lower risk for elevated systolic blood pressure (SBP) and low high-density lipoprotein cholesterol (HDL-c) (p < 0.05). ConclusionsTotal polyphenol, flavonoid and phenolic acid intakes were associated with lower odds of MetS. These intakes were also consistently and significantly associated with a lower risk for higher SBP and lower HDL-c concentrations.

Apolipoprotein mRNA in Liver and Intestine of Rats is Affected by Dietary Beet Fiber or Cholestyramine

Rats were fed a cholesterol-free diet with no added fiber (fiber-free) or with 15 g/100 g beet fiber or 5 g/100 g cholestyramine for 14 d. Final plasma total cholesterol concentrations were significantly lower in rats fed beet fiber than in those fed fiber-free or cholestyramine diets. This difference was due mainly to lower HDL cholesterol concentrations. The group fed beet fiber also tended (P < 0.1) to have lower apolipoprotein A-I concentration in plasma. Northern blot analysis revealed that the relative concentrations of jejunal apolipoprotein A-I and A-IV mRNA were the same in all groups, whereas ileal apolipoprotein A-I and A-IV mRNA levels were significantly lower in rats fed beet fiber or cholestyramine than in those fed the fiber-free diet. Hepatic apolipoprotein E mRNA concentrations were the same in all groups, but apolipoprotein A-I mRNA levels were significantly lower in rats fed beet fiber than in those fed the other diets. Apolipoprotein A-IV mRNA tended (P < 0.1) to be lower in rats fed the beet fiber diet. These data suggest that the hypocholesterolemic effect of dietary beet fiber is associated with diminished expression of the hepatic apolipoprotein A-I gene.

Atherogenic dyslipidemia and associated risk factors among hypertensive patients of five health facilities in Northeast Ethiopia.

One of the major risk factors for cardiovascular disease is atherogenic dyslipidemia. There was, however, little information available in Ethiopia. Therefore, the purpose of this study was to estimate the prevalence of atherogenic dyslipidemia and related risk factors in Northeast Ethiopian hypertension patients. A systematic random sampling technique was used to perform a cross-sectional study at an institution with 384 chosen participants. A structured questionnaire was used to collect the socio-demographic, anthropometric, lifestyle, and clinical characteristics of the respondents. Student's t-test, Mann-Whitney test, and Pearson's Chi-square test were employed to compare groups based on the type of data. Furthermore, Bivariate and multivariable logistic regression analyses were performed to identify factors independently associated with dyslipidemia. Crude and adjusted odds ratios and their corresponding 95% Confidence Intervals (CI) were computed. In all cases, statistical significance was declared at p <0.05. The majority (93.2%; 95%CI: 90.6-95.6) of patients had at least one atherogenic dyslipidemia. The prevalence of elevated total cholesterol (TC), elevated triglyceride (TG), raised low-density lipoprotein cholesterol (LDL-c), and reduced high-density lipoprotein cholesterol (HDL-c) were 47.7%, 50.3%, 44.3%, and 59.6%, respectively. Being≥ 40 years were at higher risk for having elevated levels of TC (AOR: 3.22, 95% CI: 2.40-4.32), TG (AOR: 2.30, 95% CI: 1.61-3.79), and LDL-c (AOR: 4.68, 95% CI: 2.0-10.95) than those who were below 40years. Obese participants were more likely to have high concentrations of TC (AOR: 2.57, 95%CI: 2.10-3.22), LDL-c (AOR: 3.13, 95% CI: 1.97-5.10), HDL-c (AOR: 2.71, 95% CI: 1.77-4.58), and TG (AOR: 2.23, 95%CI: 1.79-4.16). This study revealed that a high prevalence of atherogenic dyslipidemia. Thus, to prevent atherogenic dyslipidemia, it is crucial to create routine blood lipid testing programs and carry out suitable intervention programs focused on risk factor reduction.

Non-linear association between testosterone and LDL concentrations in men.

Contradictory data have been reported about the association between testosterone levels and the levels of low-density lipoprotein cholesterol (LDL). The aim of this study was to elucidate the association between testosterone and LDL levels. A cross-sectional study was conducted that included 7268 men who had participated in a health examination. Men who took agents that influence serum lipid profiles within the previous 6 months were excluded. A full metabolic work-up and serum testosterone level checks were performed. The main outcome measures included the testosterone level and testosterone<3.5ng/ml prevalence of each decile of LDL and their polynomial trendlines and the odds ratio (OR) of testosterone<3.5ng/ml according to the LDL level. The polynomial trendline suggests the inverse association of testosterone with the deciles of triglycerides, the positive association of testosterone with the deciles of high-density lipoprotein cholesterol and the inverted U-shaped association between testosterone and the deciles of LDL. The polynomial trendline suggests a U-shaped curvilinear relationship between the deciles of LDL and the prevalence of testosterone<3.5ng/ml. The adjusted ORs of testosterone<3.5ng/ml in men in the lowest and highest deciles were significantly higher than those of men in the 10th-90th deciles of LDL (OR [95% CI],<10th LDL: 1.4[1.2-1.8]; 10th - 90th LDL: 1.0 [reference];>90th LDL: 1.3[1.0-1.6]), which reinforces the U-shaped curvilinear relationship between LDL levels and the prevalence of testosterone<3.5ng/ml. Further research is needed to elucidate the association of very low or very high LDL concentrations with circulating testosterone in men.

Low HDL-Cholesterol Concentrations in Lung Transplant Candidates are Strongly Associated With One-Year Mortality After Lung Transplantation.

High-density lipoproteins (HDLs), whose main role is the reverse transport of cholesterol, also have pleiotropic anti-inflammatory, antioxidant, anti-apoptotic and anti-infectious properties. During sepsis, HDL cholesterol (HDL-C) concentration is low, HDL particle functionality is altered, and these modifications are correlated with poor outcomes. Based on the protective effects of HDL, we hypothesized that HDL-C levels could be associated with lung transplantation (LT) outcome. We thus looked for an association between basal HDL-C concentration and one-year mortality after LT. In this single-center prospective study including consecutive LTs from 2015 to 2020, 215 patients were included, essentially pulmonary fibrosis (47%) and chronic obstructive pulmonary disease (COPD) (38%) patients. Mortality rate at one-year was 23%. Basal HDL-C concentration stratified nonsurvivors to survivors at one-year (HDL-C = 1.26 [1.12-1.62] mmol/L vs. HDL-C = 1.55 [1.22-1.97] mmol/L, p = 0.006). Multivariate analysis confirmed that HDL-C concentration during the pretransplant assessment period was the only variable inversely associated with mortality. Moreover, mortality at one-year in patients with HDL-C concentrations ≤1.45mmol/L was significantly higher (log-rank test, p = 0.00085). In conclusion, low basal HDL-C concentrations in candidates for LT are strongly associated with mortality after LT. To better understand this association, further studies in this field are essential and, in particular, a better characterization of HDL particles seems necessary.