Plasma HDL Research Articles

Genome-wide investigation of DNA methylation in congenital adrenal hyperplasia

Patients with congenital adrenal hyperplasia (CAH) are at risk of long-term cognitive and metabolic sequelae with some of the effects being attributed to the chronic glucocorticoid treatment that they receive. Our pilot study investigates genome-wide DNA methylation in patients with CAH to determine whether there is preliminary evidence for epigenomic reprogramming as well as any relationship to patient outcome. Here, we analysed CD4 + T cell DNA from 28 patients with CAH (mean age = 18.5 ± 6.5 years [y]) and 37 population controls (mean age = 17.0 ± 6.1 y) with the Infinium-HumanMethylation450 BeadChip array to measure genome-wide locus-specific DNA methylation levels. Effects of CAH, phenotype and CYP21A2 genotype on methylation were investigated as well as the association between differentially methylated CpGs and glucose homeostasis, blood lipid profile, and cognitive functions. In addition, we report data on a small cohort of 11 patients (mean age = 19.1, ±6.0 y) with CAH who were treated prenatally with dexamethasone (DEX) in addition to postnatal glucocorticoid treatment.We identified two CpGs to be associated with patient phenotype: cg18486102 (located in the FAIM2 gene; rho = 0.58, adjusted p = 0.027) and cg02404636 (located in the SFI1 gene; rho = 0.58, adjusted p = 0.038). cg02404636 was also associated with genotype (rho = 0.59, adjusted p = 0.024). Higher levels of serum C-peptide was also observed in patients with CAH (p = 0.044). Additionally, levels of C-peptide and HbA1c were positively correlated with patient phenotype (p = 0.044 and p = 0.034) and genotype (p = 0.044 and p = 0.033), respectively. No significant association was found between FAIM2 methylation and cognitive or metabolic outcome. However, SFI1 TSS methylation was associated with fasting plasma HDL cholesterol levels (p = 0.035).In conclusion, in this pilot study, higher methylation levels in CpG sites covering FAIM2 and SFI1 were associated with disease severity. Hypermethylation in these genes may have implications for long-term cognitive and metabolic outcome in patients with CAH, although the data must be interpreted with caution due to the small sample size. Additional studies in larger cohorts are therefore warranted.

SUN-044 Gonadotropin Releasing Hormone (GnRH) Agonist Therapy Induces a Sustained Reduction in Plasma Testosterone Levels and Is Well Tolerated in Transwomen Veterans

Gender affirming hormone therapy (GAHT) is the mainstay of long-term management of transgender individuals. In transwomen, treatment with physiologic doses of estrogen alone is often insufficient to suppress testosterone to the desired level. Although GnRH agonist therapy is usually prescribed for puberty suppression in trans youth, in adult transwomen, GnRH agonist may be added. The durability of long-term GnRH agonist in lowering testosterone as well as the long-term safety is not clear. We examined the effect of leuprolide a GnRH agonist, on testosterone as well as clinical and metabolic features in transwomen Veterans. Out of 91 subjects with gender dysphoria followed at a VA Endocrinology clinic, 65 were transwomen (age 49 ± 3 years) who had a detailed clinical, biochemical and hormonal profile (lipid profile, HbA1C, FPG, testosterone, estradiol). We performed a retrospective cohort study of the 31 (48%) transwomen on Leuprolide (3.375mg q month) and 33 transwomen who were not on Leuprolide. Plasma testosterone, lipid profile, were analyzed before, 6 months, 1 year and at the last follow-up visit. The median follow-up of subjects on Leuprolide was 2.7 (1.7-3.8) years. Plasma testosterone concentration declined by 89% from 432±32 ng/dl to 47±9 ng/dl within 3-6 months after initiation of GnRH agonist treatment. Plasma testosterone remained persistently low 39±4ng/dl at 1 year and at the end of 2.7 yrs, most subjects on Leurprolide had plasma testosterone concentration <50ng/dl. Leuprolide therapy led to similar rapid decline in testosterone concentration in both younger (<40yrs) or relatively older (>50yr) transwomen. Leuprolide was in general well tolerated requiring discontinuation in just one patient due to severe fatigue. Three subjects (10%) experienced hot flashes which did not lead to discontinuation of medication. In the non-Leuprolide group, of 33 subjects, the follow-up was relatively inconsistent and only 12 subjects were regularly followed throughout a year with stable treatment. The decline in plasma testosterone was of a lower magnitude versus the leuprolide group (55% vs 89%, p <0.05). The testosterone levels declined from 393±42 to 180±44 ng/dl at 6 months. Body weight, and lipid profile: triglyceride, and plasma HDL concentration did not change significantly with or without GnRH agonist therapy. In conclusion, GnRH agonist therapy led to a sustained suppression of plasma testosterone levels in transwomen and was not associated with worsening lipid profile, was effective, and well tolerated in transwomen regardless of their age and may be considered an adjunct to the ant-androgen and estrogen therapy.

Real-life management of drug-drug interactions between antiretrovirals and statins.

PIs cause drug-drug interactions (DDIs) with most statins due to inhibition of drug-metabolizing enzymes and/or the hepatic uptake transporter OATP1B1, which may alter the pharmacodynamic (PD) effect of statins. To assess the management of DDIs between antiretrovirals (ARVs) and statins in people living with HIV (PLWH) considering statin plasma concentrations, compliance with dosing recommendations and achievement of lipid targets. PLWH of the Swiss HIV Cohort Study were eligible if they received a statin concomitantly with ARVs. HDL, total cholesterol (TC) and statin plasma concentration were measured during follow-up visits. Individual non-HDL and TC target values were set using the Framingham score and the 2018 European AIDS Clinical Society recommendations. Data were analysed for rosuvastatin (n = 99), atorvastatin (n = 92), pravastatin (n = 46) and pitavastatin (n = 21). Rosuvastatin and atorvastatin underdosing frequently led to suboptimal PD response. Insufficient lipid control was observed with PIs despite high atorvastatin concentrations, likely explained by inhibition of OATP1B1 resulting in less statin uptake in the liver. Target lipid values were more often achieved with unboosted integrase inhibitors due to both their favourable DDI profiles and neutral effect on lipids. Insufficient lipid control was common with pravastatin and pitavastatin regardless of co-administered ARVs and despite using maximal recommended statin doses. The latter suggests lower efficacy compared with rosuvastatin or atorvastatin. Suboptimal management of DDIs with statin underdosing was observed in 29% of prescriptions. Integrase inhibitor-based regimens and/or treatment with rosuvastatin or atorvastatin should be favoured in patients with refractory dyslipidaemia.

Intrahepatic Fat and Postprandial Glycemia Increase After Consumption of a Diet Enriched in Saturated Fat Compared With Free Sugars.

OBJECTIVEDebate continues regarding the influence of dietary fats and sugars on the risk of developing metabolic diseases, including insulin resistance and nonalcoholic fatty liver disease (NAFLD). We investigated the effect of two eucaloric diets, one enriched with saturated fat (SFA) and the other enriched with free sugars (SUGAR), on intrahepatic triacylglycerol (IHTAG) content, hepatic de novo lipogenesis (DNL), and whole-body postprandial metabolism in overweight males.RESEARCH DESIGN AND METHODSSixteen overweight males were randomized to consume the SFA or SUGAR diet for 4 weeks before consuming the alternate diet after a 7-week washout period. The metabolic effects of the respective diets on IHTAG content, hepatic DNL, and whole-body metabolism were investigated using imaging techniques and metabolic substrates labeled with stable-isotope tracers.RESULTSConsumption of the SFA diet significantly increased IHTAG by mean ± SEM 39.0 ± 10.0%, while after the SUGAR diet IHTAG was virtually unchanged. Consumption of the SFA diet induced an exaggerated postprandial glucose and insulin response to a standardized test meal compared with SUGAR. Although whole-body fat oxidation, lipolysis, and DNL were similar following the two diets, consumption of the SUGAR diet resulted in significant (P < 0.05) decreases in plasma total, HDL, and non-HDL cholesterol and fasting β-hydroxybutyrate plasma concentrations.CONCLUSIONSConsumption of an SFA diet had a potent effect, increasing IHTAG together with exaggerating postprandial glycemia. The SUGAR diet did not influence IHTAG and induced minor metabolic changes. Our findings indicate that a diet enriched in SFA is more harmful to metabolic health than a diet enriched in free sugars.

Effect of Mesenchymal Stem Cells Therapy on Cardiovascular Risk in Experimental Diabetic Kidney Disease

Abstract Background Bone Marrow-derived Mesenchymal stem cells (MSC)s were experimentally used in treating diabetes mellitus (DM) and its complications, particularly, diabetic kidney disease (DKD). Cardiovascular diseases are the leading cause of mortality in diabetic patients, which has been strongly associated with progression of DKD. Aim This study was designed to explore the effect of MSCs in modulating cardiovascular risk factors that develop with DKD. Study Design 60 adult female albino rats were allocated into three groups: control group, untreated diabetic kidney disease group (un-DKD) and MSCs treated diabetic kidney disease group (MSC-DKD). DM was induced by a single dose of Streptozotocin at a dose of 35mg/kg, then rats were sacrificed 8 weeks later. MSC-DKD rats were treated by IV injection of bone marrow-derived MSCs 4 weeks after DM induction. DKD establishment was confirmed by histopathological kidney changes and elevated plasma creatinine and urea in both un-DKD and MSC-DKD rats. Methods Blood Pressure and lipid profile were measured, and atherogenic index was calculated to assess cardiovascular risk accompanying the progression of the diabetic renal damage. Moreover, aortic reactivity studies were performed in vitro. Results A single MSCs injection to MSC-DKD rats resulted in significant decrease in final blood glucose, mean arterial blood pressure and atherogenic index, together with a significant increase in plasma HDL level compared to untreated rats, thus minimizing cardiovascular risk factors. MSC-DKD aortae also exhibited significant enhancement of vascular reactivity parameters, particularly vasorelaxation which could partially explain the improvement of blood pressure. On the other hand, DKD didn’t improve by MSCs therapy. These results conformed to tracking labelled MSCs which were found in abundance in both aortic and pancreatic tissues and absent in kidneys. Conclusion MSCs therapy holds hope of improving cardiovascular risk and mortality for diabetic patients with diabetic Kidney disease.

Model systems for studying the assembly, trafficking, and secretion of apoB lipoproteins using fluorescent fusion proteins

apoB exists as apoB100 and apoB48, which are mainly found in hepatic VLDLs and intestinal chylomicrons, respectively. Elevated plasma levels of apoB-containing lipoproteins (Blps) contribute to coronary artery disease, diabetes, and other cardiometabolic conditions. Studying the mechanisms that drive the assembly, intracellular trafficking, secretion, and function of Blps remains challenging. Our understanding of the intracellular and intraorganism trafficking of Blps can be greatly enhanced, however, with the availability of fusion proteins that can help visualize Blp transport within cells and between tissues. We designed three plasmids expressing human apoB fluorescent fusion proteins: apoB48-GFP, apoB100-GFP, and apoB48-mCherry. In Cos-7 cells, transiently expressed fluorescent apoB proteins colocalized with calnexin and were only secreted if cells were cotransfected with microsomal triglyceride transfer protein. The secreted apoB-fusion proteins retained the fluorescent protein and were secreted as lipoproteins with flotation densities similar to plasma HDL and LDL. In a rat hepatoma McA-RH7777 cell line, the human apoB100 fusion protein was secreted as VLDL- and LDL-sized particles, and the apoB48 fusion proteins were secreted as LDL- and HDL-sized particles. To monitor lipoprotein trafficking in vivo, the apoB48-mCherry construct was transiently expressed in zebrafish larvae and was detected throughout the liver. These experiments show that the addition of fluorescent proteins to the C terminus of apoB does not disrupt their assembly, localization, secretion, or endocytosis. The availability of fluorescently labeled apoB proteins will facilitate the exploration of the assembly, degradation, and transport of Blps and help to identify novel compounds that interfere with these processes via high-throughput screening.

A More Oxidized Plasma Albumin Redox State and Lower Plasma HDL Particle Number Reflect Low-Protein Diet Ingestion in Adult Rats

Plasma albumin (ALB) redox state reflects protein nutritional status, but how it differs from other protein nutrition biomarkers remains to be fully elucidated. This study aimed to delineate the characteristics of plasma ALB redox state as a protein nutrition biomarker. Adult male Wistar rats were maintained on an AIN-93 M [14% casein, control (CT)] diet or an AIN-93 M-based 5% casein [low protein (LP)] diet ad libitum for 4 wk. Plasma samples were repeatedly obtained from the same rats at weeks 0-4, ALB redox state was determined by HPLC, and the concentrations of conventional protein nutrition biomarkers, ALB and transthyretin (TTR), were compared between the groups by Student t test. Body mass, relative muscle masses, plasma proteome, and plasma lipids at week 4 were also compared. Plasma ALB redox state shifted to a more oxidized state in the LP diet group compared with the CT diet group at weeks 1-4. The LP diet group also showed significantly lower plasma ALB concentrations at weeks 1 and 2 (13% and 11% lower, respectively) and significantly lower TTR concentration at week 1 (21% lower) compared with the CT diet group, but these concentrations did not differ significantly at weeks 3 and 4. After 4 wk, body mass and relative soleus and gastrocnemius muscle masses did not differ, but the relative plantaris muscle mass tended to be 4% lower (1.75 compared with 1.68 g/kg body mass) in the LP diet group compared with the CT group (P=0.06). The LP diet group also had a significantly lower HDL particle number than the CT group (30% lower). A more oxidized plasma ALB redox state and lower plasma HDL particle number reflect LP diet ingestion in adult rats, which did not exhibit changes of plasma ALB and TTR concentrations.

Effect of dietary pomegranate by-product extract supplementation on growth performance, digestibility, and antioxidant status of growing rabbit.

The study objective was to investigate the effect of three levels of dietary pomegranate by-product extract (PBE) (100, 150, and 200mg) on growth performance, nutrient digestibility, carcass characteristics, and some blood parameters. Sixty weaned New Zealand White (NZW) rabbits at 5weeks of age with an average body weight 561.67 ± 6.68g were randomly allotted to four dietary groups; each group included three replicates (five rabbits each). The control group was fed a basal diet without PBE; the other three experimental groups fed diets supplemented with PBE at 100-, 150-, and 200-mg/kg diet. The results revealed that dietary supplementation of PBE at each level significantly (P < 0.05) improved the average final body weight and FCR. Rabbits group fed diet supplemented with 200 PBE recorded the highest (P < 0.05) of all nutrients digestibility, DCP, TDN, and DE. Feeding rabbits on diets supplemented with PBE at levels 100-, 150-, and 200-mg/kg diet increased (P < 0.05) plasma concentrations total protein, albumin, globulin, HDL, TAC, SOD, and GSH-Px, compared to the control group. The opposite trend was noticed with glucose, total lipids, triglycerides, total cholesterol, and LDL concentrations whereas they were lower (P < 0.05) than those of the control group. The obtained results also showed that PBE supplementation levels reduced (P < 0.05) both E. coli and salmonella counts in rabbit cecum. It could be concluded that the supplementation of rabbit diets with PBE at 100-, 150-, and 200-mg/kg diet improved growth performance and the nutrient digestibility. Moreover, PBE had an antioxidant and antibacterial effect of the growing rabbits.

The effectiveness of a low-fat vegan diet for the prevention and management of type 2 diabetes: A systematic review

AbstractGlobal diabetes prevalence is projected to rise from 382 million in 2013 to 592 million in 2030 with type 2 diabetes (T2D) accounting for 90–95% of cases(1,2). Approximately 4.7 million people in the UK had diabetes in 2018, this is estimated to rise to over 5 million by 2025(2) costing the NHS £15.1bn by 2035(3).Low-fat vegan (LFV) diets are associated with improvements in T2D biomarkers(4) however, to date no systematic review has evaluated the effectiveness of LFV diets in prevention and management of T2D. The aim of this study was to assess effects of LFV diets on T2D biomarkers in controlled trials for those with, or at risk of developing T2D.The review followed the PRISMA checklist for systematic reviews and used Cochrane Collaboration search strategies, which support the identification of randomised controlled trials (RCT's)(5). Searches were conducted and titles and abstracts screened for relevance by two independent review authors (AW or KEL). Studies that evaluated a LFV diet to reduce the risk of, or manage T2D using controlled trials were included with publication range from January 2003 to June 2018.Search criteria identified 130 articles, which reduced to 21 upon abstract and title screening. Further application of inclusion/exclusion criteria led to identification of six key studies. Four studies were RCT's, and two were cluster-controlled trials at corporate sites, one of which was randomised. In three of the studies participants were previously diagnosed with T2D, in two of the studies participants had a BMI ≥ 25 kg/m2 and/or were previously diagnosed with T2D, and one study had participants with BMI between 28 and 40 kg/m2. Four studies had a control group (non-intervention) two of which had a conventional diabetes diet (American Dietetic Association(6)) as a comparison group. Mean study length was 28.3 weeks; ranging from 16–74 weeks. An intention-to-treat and medication adjusted analysis was carried out; significant effects for BMI, body weight, HbA1c, fasting plasma glucose, LDL, HDL and total cholesterol were reported in most of the studies.Results from this systematic review demonstrate that a LFV diet is an effective alternative therapy to improve T2D biomarkers in those with, or at elevated risk of developing the disease. The LFV diet showed consistent positive effects on T2D biomarkers. Its effects are comparable to conventional T2D diets and energy restrictive diets, despite absence of restrictions on energy intake or portion sizes.

Comparison of Diabetogenic and Lipid Profile Among Vitamin D Deficient and Non-deficient Male Subjects

Objective: To evaluate diabetogenic and lipid profiles among subjects with or without vitamin D deficient male subjects. Design: Cross-sectional analysis Place and duration of study: From Jan- 2018 to Dec- 2018 at PNS HAFEEZ hospital Islamabad Subjects and methods: From a target population of adult male patients selected after several exclusion, we had a final total sample size of 133, which were evaluated among two groups formulated based upon whether having vitamin D deficiency or otherwise. We further compared diabetic and lipid indices including fasting plasma glucose, glycated hemoglobin (HbA1c), total cholesterol, fasting triglycerides, LDL cholesterol and HDL cholesterol among the vitamin D deficient group and vitamin D non-deficient groups by using Independent sample t-statistics. Results: HbA1c levels were higher in subjects with vitamin D deficiency [Mean: 7.43% (+2.45), n=87] in comparison to non-vitamin D deficient subjects [Mean: 6.54% (+1.67), n=45], (p=0.029). Fasting plasma glucose levels were higher in subjects with vitamin D deficiency [Mean: 8.12 mmol/L (+4.05), n=86] in comparison to non-vitamin D deficient subjects [Mean: 6.88 mmol/L (+2.85), n=43], (p=0.074). Lipid parameters did not demonstrate statistical significance among subjects with or without vitamin D deficiency. Conclusion: HbA1c and fasting plasma glucose levels were higher among subjects with vitamin D deficiency in comparison to non-vitamin D deficient male subjects.

Effects of metformin on high-fat diet-induced hyperlipidemic rats

Metformin as insulin sensitizer is now often associated with a significant decrease in plasma triglycerides, plasma total cholesterol, LDL cholesterol, and a significant increase in plasma HDL cholesterol without causing hypoglycemia. Current research aim are to determine the effects of metformin on high-fat diet-induced hyperlipidemic rats. To this end, a total of 30 Sprague-Dawley rats were divided into six groups (N = 5). Normal control was not treated, the negative group was given 0.5% CMC, the positive group used simvastatin dose of 1.8 mg/kg BW/day orally and three variation dose groups of metformin were given at a dose of 225; 450; and 900 mg/kg BW rat/day orally. Induction was carried out for 28 days and continued for 14 days treated with an administration orally. Lipid profile was measured by the colorimetric enzymatic method. As a result, all doses of metformin significantly decreased total cholesterol and LDL (p <0.05) compared to normal and negative controls. The highest dose significantly decreased triglyceride levels (p <0.05) and increased HDL levels (p <0.05) compared to normal and negative controls. Based on these results, metformin has a potential effect of antihyperlipidemic at a dose of 225 mg/kg BW rat.

Influence of CETP on High-Density Lipoprotein Subclasses in Patients with Coronary Heart Disease.

Inhibition of plasma cholesteryl ester transfer protein (CETP) can effectively reduce the risk of ath-erosclerotic cardiovascular disease by increasing high-density lipoprotein cholesterol (HDL-C) levels, but the effect of CETP on the distributions of HDL subclasses in patients with coronary heart disease (CHD) is still elusive. To investigate the correlation between the level of CETP and the distributions of HDL subclasses, 121 healthy controls and 139 patients with CHD were selected as study subjects. The plasma levels of CETP and each HDL subclass were respectively determined by enzyme-linked immunosorbent assay and two-dimensional gel electrophoresis associated with the immunodetection method. At the same time, blood biochemical data from all subjects were collected, including the levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C, apoA1, and apoB100. Correlation analysis and multiple regression analysis among the plasma HDL subclass values and biochemical parameters in subjects with CHD were conducted. As the plasma level of CETP increases, the contents of TC, TG, and apoB100/A1 were obviously elevated, while the levels of HDL-C and apoA1 decreased significantly. For distributions of HDL subclasses, large-sized HDL2a and HDL2b were markedly decreased in the middle CETP group (p < 0.05) and the high CETP group (p < 0.001) compared to the low CETP group, while the small-sized preβ1-HDL was obviously increased. Intriguingly, when the plasma concentration of TC or TG in patients with CHD was higher, the elevated preβ1-HDL and reduced HDL2a were more dependent on the increase in CETP. Furthermore, correlation analysis and multiple regression analysis also confirmed that plasma CETP was positively correlated with preβ1-HDL levels and negatively correlated with HDL2b levels. The distributions of HDL subclasses were associated with CETP in patients with CHD, especially in those with high levels of TC and TG. CETP levels were associated with an increase in small-sized preβ1-HDL and a decrease in large-sized HDL subclasses, which indicated that CETP might be a limiter of reverse cholesterol transport and HDL maturation.

Экспрессия генов ядерных факторов PPAR, LXRβ, RORα в эпикардиальной и подкожной жировой ткани у пациентов с ИБС

The nuclear factors PPARγ, RORα, and LXRβ are involved in transcriptional control of adipogenesis and implicated in glucose and lipid metabolism. In adipose tissues, they regulate inflammation. This study focuses on expression of the PPARG, RORA, and LXRβ (NR1H2) genes in epicardial and subcutaneous adipose tissues in patients with coronary heart disease as well as with concomitant abdominal obesity. In patients with coronary heart disease and abdominal obesity, PPARG mRNA level in subcutaneous adipose tissue was reduced in comparison with control group. In patients with total coronary occlusions, LXRβ mRNA level in epicardial adipose tissue was reduced, and it positively correlated with plasma HDL cholesterol. Thus, in cases of concomitant abdominal obesity and chronic total coronary occlusions, coronary heart disease is characterized by down-regulated expression of the genes of various transcriptional adipogenesis-regulating factors in adipose tissue.

Effects of High and Low Sugar Diets on Cardiovascular Disease Risk Factors.

It has been proposed that a high sugar intake was associated with cardiovascular disease (CVD) risk and metabolic syndrome depending on the amount of carbohydrate (CHO), other nutrients in foods, and underlying metabolic disturbances. This study aimed to investigate the effects of high (HS) and low sugar (LS) diets on metabolic profiles in 25 middle-aged men at increased CVD risk in a 12-week randomised cross-over intervention study. An isocaloric dietary exchanged model consisted of HS (24% energy from sugar) and LS (6% energy from sugar) with comparable total CHO, fat and fibre composition in normal foods was used. Anthropometric, blood pressure and plasma lipid profile were measured pre- and post-intervention. Body weight, waist circumference and fat mass increased and decreased significantly after HS (by 0.7±0.3 kg, 1.4±1.0 cm and 0.5±0.3 kg) and LS (by 2.1±0.5 kg, 2.0±0.8 cm and 1.4±0.3 kg) (p<0.05), respectively. Plasma TG increased significantly after HS by 0.26±0.07 mmol/L and decreased after LS by 0.35±0.16 mmol/L. Plasma HDL decreased by 0.11±0.03 mmol/L (p<0.05) after HS, whilst, plasma TC and LDL decreased significantly by 10% after LS. There was no significant change in other parameters after either diet. This study confirmed that a diet with a greater proportion of sugar increased CVD risk via negative changes in metabolic profiles including body weight, waist circumference and lipid parameters, whereas LS produced the positive effects. A restriction of sugar intake to lower than 10% energy intake is vital to reduce CVD risk.

Effects of salt reduction on cardiovascular risk factors. The STRIVE-study. A 4-month randomized controlled study among healthy families

AbstractDietary salt intake in most countries is far beyond the recommended level and many countries have initiated national programs to decrease salt intake. However, potential adverse effects of reducing salt intake in the general population are currently discussed. Hence some randomized studies have shown adverse effects on plasma lipids, the renin-angiotensin-aldosterone system and the sympathetic nervous system, which may again increase risk of CVD. These findings are however mainly based on short-term studies with a very large acute salt reduction. This study aims to explore the effect of gradually reducing salt intake in a real life setting according to recommendations, and to examine the effect of different salt reduction strategies among families.The study was a 4-month cluster randomized controlled trial with families randomly assigned to either A) salt reduced bread, B) salt reduced bread and dietary counselling or C) standard bread (control) Participants in intervention A received bread gradually reduced in salt content from 1.2 g salt/100 g (regular) to 0.6 g salt/100 g in ryebread and 0.4 g salt/100 g in wheat bread. Participants in intervention B received the same salt reduced bread and in addition, they received dietary advise on how to further reduce their salt intake and promote potassium. The control group received regular bread. Changes in outcomes were assessed using linear mixed models.Results: A total of 89 families (155 adults; 156 children) from the suburb of Copenhagen, Denmark, participated in the study (February-July 2018). A total of 291 (94%) participants completed the intervention. Results presented are preliminary.Intention to treat analyses showed no significant effects of the salt reduction intervention on changes in systolic and diastolic blood pressure, plasma triglyceride. A small, but significant (-0.26 mmol/l; P = 0.02) decrease in total plasma cholesterol was shown in intervention group A. A similar, but non-significant, tendency was found in intervention group B. (more results will follow).Subgroup analyses, including only participants in the intervention groups that decreased their salt intake by at least 20% from baseline to 4-month follow-up, showed a significant decrease in diastolic (-3.5 mmHg; P &lt; 0.0001) and systolic (-6.3 mmHg; P &lt; 0.0001) blood pressure, total plasma cholesterol (-0.25 mmol/l; P = 0.0009), LDL plasma cholesterol (logarithm transformed) (-6%; P = 0.03) and plasma triglyceride (logarithm transformed) (-17%; P = 0.04). No significant effects were found for HDL plasma cholesterol, aldosterone, renin, plasma glucose and HbA1c.Conclusion: Reduced salt intake were associated with beneficial changes in cardiovascular risk factors. No adverse effects were observed.

Prevalence of cardiac dysfunction in type 2 diabetes in a tertiary health care setup

Introduction: Diabetes mellitus (DM) may be one factor that specifically influences cardiac diastolic function. The present study was designed to examine cardiac dysfunction in diabetes subjects with non-chronic renal failure (CRF). Materials and methods: Study was approved by Institutional ethics committee, Informed consent from the study subjects. Diagnosis of diabetes was made according to WHO criteria. Plasma glucose concentration, serum lipids (total cholesterol, triglycerides, LDL cholesterol and HDL plasma cholesterol concentrations) were measured as per standard procedures. Glycosylated hemoglobin (HbA1c) was estimated by ion exchange resin method. ECG recording was obtained for every subject to rule out ischemic heart disease. Results: Of the 150 study Type 2 diabetes participants, the male female ratio was 1.1. The mean HbA1C was 9.112±1.36 %. 2D ECHO findings showed 34% left ventricular hypertrophy and 51.3% diastolic dysfunction. Dyslipidemia was identified in 54.7% and statistically there was no significant association between dyslipidemia and diastolic dysfunction (P = 0.532). Conclusion: In this study, diastolic dysfunction dyslipidemia was identified in 51.5% participants without dyslipedemia. Though, there was no significant difference, this number is to be considered. However, studies should be conducted with big samples size.

Development of Low Glycemic Index Rice and Its Effectiveness in the Regulation of Postprandial Glucose Response in Type 2 Diabetes

Background/Objective: To determine the glycemic index (GI) of RNR15048 rice variety and study its effectiveness in reducing postprandial blood glucose levels and the regulation of lipid profile in patients with type 2 diabetes. Subjects/Methods: The GI of RNR15048 rice was measured in 54 healthy subjects in the age group of 30-50 years. The dietary intervention study was conducted in 80 subjects with diabetes in the age group of 40-60 years where 40 test subjects replaced their regular rice with RNR 15048 rice variety for 3 months. Anthropometric and biochemical parameters, HbA1c, fasting blood glucose, lipid profile, insulin were determined before and after the study. Results: The glycemic index (GI) of RNR 15048 rice variety was observed to be low with GI of 51.72 ± 3.39. The dietary intervention study in type 2 diabetic subjects revealed significant decrease in fasting blood glucose (158.4 ± 9.30 vs 140.2 ± 8.87 mg/dL) and HbA1c levels (7.1 ± 0.34 vs 6.1 ± 0.33 %) with an increase in HDL levels (33.7 ± 1.29 vs 37.1 ± 1.83 mg/dL) while parameters such as body weight, blood pressure and insulin levels did not show any significant changes. Conclusion: Low GI rice is effective in the reduction of postprandial glucose response in type 2 diabetes and increase in plasma HDL levels and therefore useful in the management of type 2 diabetes and in the long term management of cardiovascular diseases.

Reduced CETP glycosylation and activity in patients with homozygous B4GALT1 mutations.

The importance of protein glycosylation in regulating lipid metabolism is becoming increasingly apparent. We set out to further investigate this by studying the effects of defective glycosylation on plasma lipids in patients with B4GALT1‐CDG, caused by a mutation in B4GALT1 with defective N‐linked glycosylation. We studied plasma lipids, cholesteryl ester transfer protein (CETP) glyco‐isoforms with isoelectric focusing followed by a western blot and CETP activity in three known B4GALT1‐CDG patients and compared them with 11 age‐ and gender‐matched, healthy controls. B4GALT1‐CDG patients have significantly lowered non‐high density lipoprotein cholesterol (HDL‐c) and total cholesterol to HDL‐c ratio compared with controls and larger HDL particles. Plasma CETP was hypoglycosylated and less active in B4GALT1‐CDG patients compared to matched controls. Our study provides insight into the role of protein glycosylation in human lipoprotein homeostasis. The hypogalactosylated, hypo‐active CETP found in patients with B4GALT1‐CDG indicates a role of protein galactosylation in regulating plasma HDL and LDL. Patients with B4GALT1‐CDG have large HDL particles probably due to hypogalactosylated, hypo‐active CETP.

Risk factors of systematic biliary complications in patients with gallbladder stones.

Gallbladder stone with symptom is an indication of cholecystectomy according to the current guideline. However, about 80% of gallstone patients are asymptomatic. The identification of gallbladder stone patients likely to develop symptomatic complications would be of benefit in clinical practice. The aim of this study was to investigate the risk factors for asymptomatic gallstone diseases developing into a gallstone-related biliary event. This retrospective study evaluated 1284 patients with gallstones and received laparoscopic cholecystectomy (LC) in Peking Union Medical College Hospital. The age-gender-matched patients were divided into the acute cholecystitis group (group A), biliary colic group (group B), and asymptomatic gallstone group (group C). Baseline clinical characteristics and serum biochemical indexes were recorded and analyzed among the groups. Univariate logistic regression and multivariate Cox proportional hazard regression analysis were performed to determine the risk factors. The incidence of diabetes, hypertension, and sludge was higher in group A than in group B and in group C. The concentrations of plasma HDL in group A were lower than those in group B and group C (P <0.05, 1.12 ± 0.19, vs. 1.21 ± 0.22, vs. 1.21 ± 0.21). Logistic regression analysis showed that diabetes (OR = 1.39, 95% CI 1.07-1.56, P =0.028), sludge (OR = 1.09, 95% CI 1.01-1.18, P =0.022), HDL (OR = 0.85, 95% CI 0.70-1.02, P =0.045), and FBG (1.91, 95% CI 1.26-2.90, P =0.034) were significantly associated with biliary events. Diabetes, sludge, and lower blood HDL level are risk factors for symptomatic gallstone diseases.

Urinary Ethyl Glucuronide Can Be Used as a Biomarker of Habitual Alcohol Consumption in the General Population

ABSTRACTBackgroundAlcohol consumption is a frequently studied risk factor for chronic diseases, but many studies are hampered by self-report of alcohol consumption. The urinary metabolite ethyl glucuronide (EtG), reflecting alcohol consumption during the past 72 h, is a promising objective marker, but population data are lacking.ObjectiveThe objective of this study was to assess the reliability of EtG as a marker for habitual alcohol consumption compared with self-report and other biomarkers in the general population.MethodsAmong 6211 participants in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort, EtG concentrations were measured in 24-h urine samples. EtG was considered positive when concentrations were ≥100 ng/mL. Habitual alcohol consumption was self-reported by questionnaire (categories: no/almost never, 1–4 units per month, 2–7 units per week, 1–3 units per day or ≥4 units per day). Plasma HDL cholesterol concentration, erythrocyte mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltransferase (GGT) were determined as indirect biomarkers of alcohol consumption. Sensitivity, specificity, positive and negative predictive value, and proportions of agreement between reported consumption and EtG were calculated. To test the agreement of EtG concentration and alcohol consumption in categories, linear regression analysis was performed. In addition, the association between EtG concentrations and indirect biomarkers was analyzed.ResultsMean age was 53.7 y, and 52.9% of participants men. Of the self-reported abstainers, 92.3% had an EtG concentration <100 ng/mL. Sensitivity was 66.3%, positive predictive value was 96.3%, and negative predictive value was 47.4%. The proportion of positive agreement was 78.5%, and the proportion of negative agreement was 62.7%. EtG concentrations were linearly associated with higher categories of alcohol consumption (P-trend < 0.001), adjusted for age, sex, and renal function. EtG was positively related to MCV, HDL cholesterol, and GGT but not to AST and ALT concentrations.ConclusionsThis study shows that urinary EtG is in reasonable agreement with self-reported alcohol consumption and therefore can be used as an objective marker of habitual alcohol consumption in the general population.