Decreased Serum High-density Lipoprotein Cholesterol Research Articles

Lipids and sudden sensorineural hearing loss: A bidirectional two-sample Mendelian randomization analysis

ObjectiveWhile numerous observational studies have indicated an association between lipids and Sudden Sensorineural Hearing Loss (SSNHL), it remains uncertain whether dyslipidemia serves as a causal risk factor for SSNHL. Our objective is to elucidate the potential causal relationship between lipid levels and SSNHL through Mendelian randomization analysis. MethodsThe primary and secondary lipid data used in this study were sourced from the UK Biobank (UKBB) and the Global Lipid Genetics Consortium results (GLGC), respectively. These datasets were obtained from large, publicly available genome-wide association studies (GWAS). The outcome data for sudden sensorineural hearing loss (SSNHL) were acquired from the Finnegan Biobank, consisting of 1491 cases and 196,592 controls. Subsequently, both single-variable Mendelian randomization (SVMR) and multivariate Mendelian randomization (MVMR) methods were employed to evaluate the causal relationship between lipids and the occurrence of SSNHL. ResultsAmong the primary lipid data, SVMR analysis showed a significant correlation between high density lipoprotein cholesterol (HDL-C) (OR: 0.822, 95 %CI: 0.694–0.974, p = 0.023) and SSNHL, and triglycerides (TG) (OR: 0.997, 95 %CI: 0.836–1.188, p = 0.975), low density lipoprotein cholesterol (LDL-C) (OR: 1.067, 95 %CI: 0.861–1.322, p = 0.552) did not correlate with SSNHL. In the secondary lipid data, SVMR analysis showed that HDL-C (OR: 0.987, 95 %CI: 0.805–1.210, p = 0.903), TG (OR: 0.991, 95 %CI: 0.787–1.246, p = 0.937) and LDL-C (OR: 1.092, 95 % CI: 0.926–1.287, p = 0.294) did not correlate with SSNHL. MVMR analysis of the primary lipid data showed that HDL-cholesterol (OR: 0.755, 95 % CI: 0.596–0.956, p = 0.019) was significantly associated with SSNHL, while TG (OR: 0.808, 95 %CI: 0.611–1.068, p = 0.134) and LDL-C (OR: 1.146, 95 %CI: 0.869–1.511, p = 0.333) did not correlate with SSNHL, consistent with the results of SVMR. Inverse MR results showed that SSNHL did not correlate with TG (OR: 0.999, 95 %CI: 0.997–1.001, p = 0.835), HDL-C (OR: 1.001, 95 %CI: 0.998–1.003), LDL-C (OR: 0.999, 95 %CI: 0.997–1.002, p = 0.863). ConclusionsMendelian randomization (MR) results suggest that decreased serum HDL-C levels are an independent risk factor for SSNHL. Monitoring and focusing on lipid levels may be of value in the prevention and treatment of SSNHL.

Influence of inflammation on lipid profile in chronic rheumatic diseases

Chronic inflammatory rheumatic diseases are associated with an increased risk of cardiovascular disease. In this group of patients, inflammation causes various changes in lipid metabolism, which in a chronic course may contribute to an increased risk of atherosclerosis. The most frequent abnormality is decreased serum high-density lipoprotein cholesterol (HDL–C) and increased triglyceride (TG) levels. This imbalance may be due to increased production and secretion of very low-density lipoprotein cholesterol (VLDL–С) in the liver and decreased clearance of TG-rich lipoproteins. The mechanisms by which inflammation lowers HDL–C levels are still unclear. Additionally, there is a persistent increase in lipoprotein (a) (Lp[a]) due to its increased synthesis. Thus, systemic inflammation negatively affects lipoprotein function: LDL–C oxidation becomes more active since there is the decreased ability of HDL–C to prevent this pathway. Moreover, chronic inflammation adversely affects the reverse cholesterol transport mechanism. The greater the severity of the underlying disease is associated with the more pronounced disorders in lipid metabolism. In general, approaches to the correction of lipid metabolism in patients with inflammatory rheumatic diseases are similar to those in patients from the general population.

The Effects of Atorvastatin Consumption on Biochemical Variables in Patients with Type 2 Diabetes Mellitus and Pre-diabetes

Background and Aims: Atorvastatin may alter glycemic traits and lipid profiles. This study aimed to evaluate the effects of atorvastatin on biochemical variables in patients with type 2 diabetes and pre-diabetes (borderline diabetes).
 Materials and Methods: This study included 80 individuals divided into five groups. Patients with type 2 diabetes mellitus and pre-diabetes used atorvastatin 20 mg/day for three months. After three months, variables such as serum fasting blood glucose (FBS), cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and glycosylated hemoglobin (HbA1c) levels were measured to assess the status of diabetes and pre-diabetes condition. Linear regression was applied to determine the association between atorvastatin uses and alters of biochemical variables levels.
 Results: The serum FBS and HbA1c levels in patients with diabetes and pre-diabetes who use atorvastatin were significantly lower than in patients with diabetes and pre-diabetes who did not use atorvastatin (p=0.001). Serum cholesterol and LDL-C levels decreased in diabetic and pre-diabetic patients who used atorvastatin in comparison with diabetic and pre-diabetic patients who did not use atorvastatin (p=0.001). In patients with pre-diabetes, the use of atorvastatin slightly increased serum HDL-C levels. However, in patients with diabetes, the use of atorvastatin slightly decreased serum HDL-C level (p= 0.001). Diabetic and pre-diabetic patients who use atorvastatin significantly decreased serum triglyceride levels (p=0.016), while in diabetic and pre-diabetic patients, using atorvastatin slightly increased the serum insulin level (p= 0.003).
 Conclusions: Atorvastatin using alters fat and sugar indices in diabetic and pre-diabetic patients.

Significance of Decreased Serum High-density Lipoprotein Cholesterol Levels in Patients with Gastric Cancer

Significance of Decreased Serum High-density Lipoprotein Cholesterol Levels in Patients with Gastric Cancer

DGAT2-MOGAT2 SNPs and Gene-Environment Interactions on Serum Lipid Profiles and the Risk of Ischemic Stroke.

Background: The genetic susceptibility to ischemic stroke (IS) is still not well-understood. Recent genome-wide association studies (GWASes) found that several single nucleotide polymorphisms (SNPs) in the Diacylglycerol acyltransferase 2 gene (DGAT2) and monoacylglycerol O-acyltransferase 2 (MOGAT2) cluster were associated with serum lipid levels. However, the association between the DGAT2-MOGAT2 SNPs and serum lipid phenotypes has not yet been verified in the Chinese people. Therefore, the present study was to determine the DGAT2-MOGAT2 SNPs and gene-environment interactions on serum lipid profiles and the risk of IS.Methods: Genotyping of 5 SNPs (DGAT2 rs11236530, DGAT2 rs3060, MOGAT2 rs600626, MOGAT2 rs609379, and MOGAT2 rs10899104) in 544 IS patients and 561 healthy controls was performed by the next-generation sequencing technologies. The association between genotypes and serum lipid data was determined by analysis of covariance, and a corrected P-value was adopted after Bonferroni correction. Unconditional logistic regression analysis was performed to assess the association between genotypes and the risk of IS after adjustment of potential confounders.Results: The rs11236530A allele was associated with increased risk of IS (CA/AA vs. CC, OR = 1.45, 95%CI = 1.12–1.88, P = 0.0044), whereas the rs600626G-rs609379A-rs10899104G haplotype was associated with decreased risk of IS (adjusted OR = 0.67, 95% CI = 0.48–0.93, P = 0.018). The rs11236530A allele carriers had lower high-density lipoprotein cholesterol (HDL-C) concentrations than the rs11236530A allele non-carriers (P < 0.001). The interactions of rs11236530-smoking, rs3060-smoking and rs10899104-smoking influenced serum apolipoprotein B levels, whereas the interactions of rs11236530- and rs3060-alcohol affected serum HDL-C levels (PI < 0.004–0.001). The interaction of rs600626G-rs609379A-rs10899104G-alcohol (OR = 0.41, 95% CI = 0.22–0.76) and rs600626G-rs609379C-rs10899104T-alcohol (OR = 0.12, 95% CI = 0.04–0.36) decreased the risk of IS (PI < 0.0001).Conclusions: The rs11236530A allele was associated with decreased serum HDL-C levels in controls and increased risk of IS in patient group. The rs600626G-rs609379A-rs10899104G haplotype, the rs600626G-rs 609379A-rs10899104G-alcohol and rs600626G-rs609379C-rs10899104T-alcohol interactions were associated with decreased risk of IS. The rs11236530 SNP may be a genetic marker for IS in our study populations.

Orally administered octacosanol improves some features of high fructose-induced metabolic syndrome in rats.

We examined whether orally administered octacosanol, a long-chain aliphatic saturated alcohol, improves the features of high fructose-induced metabolic syndrome in rats. Five-week-old rats were fed a high fructose diet containing 60% fructose for 3 weeks. Then, the high fructose fed rats received a daily single oral administration of octacosanol (10 or 100 mg/kg body weight) with high fructose feeding for one week. Three- or four-week high fructose feeding increased insulin resistance, serum insulin, triglyceride, total cholesterol, free fatty acids, uric acid, and lipid peroxide concentrations, and hepatic triglyceride and cholesterol contents significantly and decreased serum high-density lipoprotein cholesterol and adiponectin concentrations significantly but did not affect blood pressure and hepatic lipid peroxide and reduced glutathione contents. Four-week high fructose feeding decreased hepatic ascorbic acid content significantly. Oral administration of octacosanol (10 or 50 mg/kg body weight) to high fructose-fed rats for the last 1-week fructose diet feeding attenuated these changes except serum insulin level and insulin resistance significantly and increased hepatic reduced glutathione content significantly. The higher dose of Oct decreased hepatic lipid peroxide content significantly. These results indicate that orally administered octacosanol improves dyslipidemia, hyperuricemia, hypoadiponectinemia, and oxidative stress associated with the features of high fructose-induced metabolic syndrome rats.

Maternal fructose consumption down-regulates Lxra expression via miR-206-mediated regulation

Maternal fructose consumption affects the metabolic functions of offspring later in life. However, the molecular mechanism remains poorly understood. Differences of microRNA expression profile and DNA methylation status are a candidate mechanism to explain the developmental programming that contributes to the development of a metabolic disorder. This study examined the transgenerational effect of maternal fructose consumption from the perspective of epigenetic modification. To do this, we collected serum and liver tissues from male offspring rats that were exposed to maternal distilled water or 20% fructose water during gestation and lactation. A decreased serum high-density lipoprotein cholesterol (HDL-C) level was observed in the offspring of fructose-fed dams at postnatal day (PD) 160. Given research indicating a role of liver X receptor alpha (LXRA) in cholesterol metabolism, we analyzed Lxra expression. Real-time polymerase chain reaction analysis demonstrated that offspring that were delivered from fructose-fed dams exhibited decreased Lxra gene expression in their liver tissue. There is a well-established association between Lxra expression and the level of DNA methylation and miR-206 expression. Pyrosequencing assays revealed no differences in the level of DNA methylation in the Lxra promoter region, whereas miR-206 expression was increased in the liver at PD 60 and 160. Our data indicate that early-life exposure to maternal fructose results in changing of miR-206 expression level in the liver that suppresses the expression of Lxra. This phenomenon may be associated with the decreased serum HDL-C level in offspring.

Dyslipidemia and cardiovascular disease risk among the MASHAD study population

IntroductionDyslipidemia may be defined as increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration. Dyslipidemia is an established risk factor for cardiovascular disease (CVD). We aimed to investigate the association of dyslipidemia and CVD events among a population sample from Mashhad, in northeastern Iran.Material and methodsThis prospective cohort study comprised a population of 8698 men and women aged 35–65 years who were recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. Socioeconomic and demographic status, anthropometric parameters, laboratory evaluations, lifestyle factors, and medical history were gathered through a comprehensive questionnaire and laboratory and clinical assessment for all participants. Cox regression model and 95% confidence interval (CI) were used to evaluate the association of dyslipidemia and its components with CVD incidence.ResultsAfter 6 years of follow-up, 233 cases of CVD (including 119 cases of unstable angina [US], 74 cases of stable angina [SA], and 40 cases of myocardial infarction [MI]) were identified in the study population. Unadjusted baseline serum LDL-C, TC, and TG levels were positively associated with the risk of total CVD events among the entire population (HR: 1.54, 95% CI: 1.19–2; P-value< 0.01; HR: 1.53; 95% CI: 1.18–1.98; P < 0.01; HR: 1.57; 95% CI: 1.27–2.03; P < 0.01, respectively). However, after adjusting for confounding factors (age, body mass index [BMI], family history of CVD, smoking status [non-smoker, ex-smoker and current smoker], lipid lowering drug treatment, anti-hypertensive drug treatment, hypertension, healthy eating index [HEI], total energy intake, and presence of diabetes mellitus), a significant direct association only remained between TC and MI risk in men (HR: 2.71; 95%CI: 1.12–6.57; P-value< 0.05).ConclusionIn the present study, TC baseline level was significantly associated with the risk of MI among men.

Current status of the reference system for measurement of serum high- and low-density lipoprotein cholesterol

Decreased serum high-density lipoprotein cholesterol (HDL-C) and increased low-density lipoprotein cholesterol (HDL-C) concentrations are important risk factors for cardiovascular diseases. Achieving accurate and comparable HDL-C and LDL-C results is the primary requirement for the prevention and treatment of cardiovascular diseases, in which reference system including reference method, reference materials and standardization programs are needed. The current reference method for HDL-C and LDL-C measurement is the β-quantification method developed by the United States Center for Disease Control and Prevention (CDC), a multi-step procedure involving ultracentrifugation, chemical precipitation, and cholesterol analysis by CDC reference method. This method uses a large amount of serum and is technically demanding which limited its application in standardization. The reduced volume β-quantification method uses a small volume of serum sample, is simple and high through put and is more applicable. However, both methods are sensitive to serum matrix. Commutability of reference materials should be evaluated when they are used to calibrate routine methods. Fresh (non-frozen) serum samples should be used for a split sample comparison between reference and direct methods. In addition, development of reference measurement procedure based on ultracentrifugation and preparation of commutable reference materials are the important work in lipoprotein standardization. Key words: Cholesterol,HDL; Cholesterol,LDL; Ultracentrifugation; Reference standards; Reproducibility of results

The effect of chronic intermittent hypoxia on serum high-density lipoprotein cholesterol and the expressions of peroxisome proliferators-activated receptors .ALPHA. and adenosine triphosphate binding cassette transporter Al in rat liver tissues

Objective To investigate the effect of chronic intermittent hypoxia(CIH)on serum high-density lipoprotein cholesterol(HDL-C)and the changes of HDL-C metabolism-related indicators such as the expressions of peroxisome proliferators-activated receptor α(PPARα)and adenosine triphosphate binding cassette transporterA1(ABCA1)in liver in male SD rats. Methods Obstructive sleep apnea syndrome(OSAHS)-induced CIH rats were randomly allocated into 6 groups: 10%CIH-3 weeks, 5%CIH-3 weeks, 5%CIH-3 weeks + RH(Removal of hypoxia-3 weeks), 10%CIH-3 weeks + RH(Removal of hypoxia-3 weeks), control group-3 weeks, and control group-6 weeks.Serum lipids were measured and compared.To observe and compare the liver pathology, the expression levels of PPARα and ABCA1 in liver tissue of CIH rats were detected by immunohistochemical method. Results The levels of serum TC, TG and LDL-C was significantly higher in CIH rats than in control group.The levels of TC, TG and LDL-C were significantly lower in reoxygenation groups than in CIH groups.There was no significant difference between experiment groups and correspondent control groups(all P>0.05). Compared with control group, CIH rats had significantly lower levels of serum HDL-C; Compared with CIH groups, the levels of HDL-C were significantly higher in reoxygenation groups.There was no significant difference between experiment groups and correspondent control groups(all P>0.05). Compared with control group, the expression of PPARα and ABCA1 of CIH group was significantly lower; Compared with CIH groups, the expression of PPARα and ABCA1 was significantly higher in reoxygenation groups; There was no significant difference in the expression of PPARα and ABCA1 between reoxygenation groups and correspondent control groups, in which the oxygen level was recovered to normal. Conclusions The serum HDL-C level was obviously decreased in OSAHS-induced CIH rats, and the decreased serum HDL-C can be effectively improved by reoxygenation intervention.OSAHS-induced CIH may lead to the dyslipidemia through PPARα-ABCA1 pathway, and reoxygenation intervention for three weeks can effectively recover the expression levels of PPARα and ABCA1 to normal levels, which suggests that if CIH is effectively intervented, the change of PPARα and ABCA1 of liver can be reversed, thereby reversing dyslipidemia. Key words: Sleep apnea, obstructive; Anoxia; Cholesterol, HDL

Relationship between vascular function indexes, renal arteriolosclerosis, and renal clinical outcomes in chronic kidney disease.

Hypertension contributes critically to the development of renal arteriolosclerosis in chronic kidney disease (CKD), but the impact of vascular function indexes including central blood pressure on renal arteriolosclerosis has not been investigated. We determined whether vascular function indexes were related to renal arteriolosclerosis and renal clinical outcomes in CKD. This cross-sectional study was implemented in our hospital. Subjects were in-patients with CKD aged ≥20 years who underwent a renal biopsy. Vascular function indexes included central systolic blood pressure (SBP), cardio-ankle vascular index (CAVI), and renal resistive index. Central SBP was measured non-invasively using an automated device. Arteriolosclerosis was assessed histologically. Renal clinical outcomes included estimated glomerular filtration rate using serum creatinine (eGFRcreat) or cystatin C (eGFRcys), and the urinary albumin-creatinine ratio. Among vascular function indexes, central SBP was weakly correlated with renal arteriolosclerosis (n = 55). Renal arteriolosclerosis was increased in hypertensive or hyperuricaemic patients, and negatively correlated with serum high-density lipoprotein (HDL) cholesterol and eGFRcys, which were independent risk factors for renal arteriolosclerosis in a stepwise multivariate regression analysis. Of the vascular function indexes, CAVI showed the strongest correlation with all renal clinical outcomes. Central SBP was correlated with only urinary albumin-creatinine ratio, while renal resistive index was correlated with eGFRcreat and urinary albumin-creatinine ratio. Decreased serum HDL cholesterol was independently and most closely associated with renal arteriolosclerosis. Of the vascular function indexes, CAVI had the greatest impact on renal clinical outcomes, although it was not associated with renal arteriolosclerosis.

The Relationship between Reproductive Hormones and Metabolic Parameters in Women with Polycystic Ovary Syndrome

Background: Polycystic ovarian syndrome (PCOS) is a condition associated with chronic anovulation, and androgen excess. Clinically, PCOS women usually presents with menstrual irregularities, infertility, and hirsutism. Women with this syndrome are at increased risk of metabolic syndrome (MS).Patients and Methods: This study was conducted during the period from March 2013 until the end of September 2013. A total of 50 PCOS women were studied (25 PCOS women with MS and 25 PCOS women without MS) with an age ranged from (35-45) years. Women with PCOS were referred to Medical City Hospital in Baghdad and compared with 25 healthy women as control group. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, progesterone, testosterone, fasting serum glucose (FSG), serum triacylglycerol (TAG), and high density lipoprotein cholesterol (HDL-C) were measured for each individuals.Objective: To study the characteristics of the MS in women with PCOS.&#x0D; Results: Means of FSG, TAG, LH, prolactin, progesterone, testosterone levels, and LH/FSH ratio were significantly elevated in PCOS women than in the control group, while serum HDL-C levels were significantly lowered in PCOS women than in the control. There was a significant increase in FSG and TAG in PCOS women with MS as compared to PCOS women without MS, (P=0.0001). While, there was a significant decrease in serum HDL-C in PCOS women with MS as compared to PCOS women without MS. No significant differences were found in LH, FSH, prolactin, progesterone, testosterone, LH/FSH ratio, day of menstrual cycle, and duration of infertility between PCOS women with and without MS. Conclusions: The present study showed that PCOS women with MS had abnormalities in hormonal and lipid profile.

Curcumin ameliorates streptozotocin-induced heart injury in rats.

Heart failure (HF) is one of diabetic complications. This work was designed to investigate the possible modulatory effect of curcumin against streptozotocin-induced diabetes and consequently HF in rats. Rats were divided into control, vehicle-treated, curcumin-treated, diabetic-untreated, diabetic curcumin-treated, and diabetic glibenclamide-treated groups. Animal treatment was started 5 days after induction of diabetes and extended for 6 weeks. Diabetic rats showed significant increase in serum glucose, triglycerides, total cholesterol, low-density lipoprotein-cholesterol, very low density lipoprotein-cholesterol, nitric oxide, lactate dehydrogenase, cardiac malondialdehyde, plasma levels of interleukin-6, and tumor necrosis factor-alpha, and also showed marked decrease in serum high-density lipoprotein-cholesterol, cardiac reduced glutathione, and cardiac antioxidant enzymes (catalase, superoxide dismutase, and glutathione-S-transferase). However, curcumin or glibenclamide treatment significantly mitigated such changes. In conclusion, curcumin has a beneficial therapeutic effect in diabetes-induced HF, an effect that might be attributable to its antioxidant and suppressive activity on cytokines.

1,3-Dichloro-2-propanol induced hyperlipidemia in C57BL/6J mice via AMPK signaling pathway

1,3-Dichloro-2-propanol (1,3-DCP) is a well-known contaminant that has been detected in a wide range of foods. Dietary intake represents the greatest source of exposure to 1,3-DCP. In the study, we first found 1,3-DCP could induce hyperlipidemia in C57BL/6J mice below 1mg/kg/day. We investigated serum lipid profile, liver total cholesterol (TC) and triglyceride (TG), histopathology of Liver and adipose tissue. The results showed 1,3-DCP dose dependently increased serum TG, TC and low-density lipoprotein cholesterol (LDL-C), decreased serum high-density lipoprotein cholesterol (HDL-C), increased relative liver weight, liver TG and TC, relative adipose tissue weight and enlarged the size of adipose cells. Because AMPK signal pathway is important in the process of lipid metabolism, we further investigated the effects of 1,3-DCP on AMPK signaling pathway in murine models. The results showed that 1,3-DCP (0.1–1mg/kg/day) decreased p-AMPK/tAMPK ratio, p-ACC/tACC ratio, PPARα expression, but increased FAT, SREBP1, HMGCR and FAS expression. These observations indicated that 1,3-DCP induced hyperlipidemia in C57BL/6J mice at least partially through regulating AMPK signaling pathway.

Lipid Profile of Patients with Acute Myocardial Infarction and its Correlation with Systemic Inflammation

The biomarker potential of using various lipids fractions for predicting risk of acute myocardial infarction (AMI) is controversial. We therefore compared the lipid profiles, including serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) and triglycerides (TG), in 67 AMI patients. Patients included 28 STEMI (ST-elevated myocardial infarction) patients, 39 NSTEMI (non-ST-elevated myocardial infarction) patients and 25 patients with chest pain. Control group included 54 age- and gender-matched normal subjects. We also studied the correlation between lipid profile and systemic inflammation in these subjects. There were significant decreases in TC, LDL and HDL levels in both STEMI and NSTEMI patients as compared to normal subjects; however, patients with chest pain did not show any significant change in these lipids. Serum TG levels did not differ significantly among the study groups. There were significant increases in serum high-sensitive C-reactive protein (hs-CRP) levels in STEMI and NSTEMI patients, as compared to control group. Serum hs-CRP showed significant inverse correlation with HDL; however, hs-CRP was not correlated with TC, LDL, and TG. In conclusion, our findings suggest that reduction in serum TC does not prevent the risk of AMI, whereas a decrease in serum HDL and increase in hs-CRP strongly predisposes the risky individuals to an AMI event. We emphasize the importance of HDL and CRP measurements for the assessment of a combined lipid-inflammation risk factor that could be a useful predictor of high risk individuals, as well as a prognostic marker in AMI patients.

Serum Lipid Profile status of Type 2 Diabetic Patients in the cross section population in Dhaka City of Bangladesh

Objectives: Serum lipid profile viz the level of total cholesterol (TC), Triglyceride (TG), HDL-cholesterol and LDL-cholesterol of type2 diabetic patients have been studied and compares them with levels of control subjects. Results: The mean value of the TG level for male diabetics was higher than that for the female diabetics and the mean values of TC, HDL-C and LDL-C were not found significantly different between male and female diabetics. Hyperlipidemia has a documented causative relation with CAD, but the major risk associated with diabetes may be due to the associated hyperlipidemia. The study revealed that dyslipidemia is very common in type2 diabetics and the most common abnormality observed was increased serum triglyceride levels (58%). The next common abnormality was decreased serum high-density lipoprotein cholesterol (HDL-C) levels and increased serum low-density lipoprotein cholesterol (LDL-C) levels. A high total serum cholesterol levels was found in 41% patients. 39% of the patients examined were overweight, and 7% were overtly obese. Conclusion: Thus, the study clearly shows the relationship between type2 diabetes and hyperlipidemia, which may influence the mechanism by which type2 diabetes is associated with increased CAD risk. DOI: http://dx.doi.org/10.3329/bjms.v11i2.11479 Bangladesh Journal of Medical Science Vol. 11 No. 02 April 2012: 121-125

Inhibition of Apolipoprotein A‐I Gene Expression by Obesity‐Associated Endocannabinoids

Obesity is associated with increased serum endocannabinoid (EC) levels and decreased high-density lipoprotein cholesterol (HDLc). Apolipoprotein A-I (apo A-I), the primary protein component of HDL is expressed primarily in the liver and small intestine. To determine whether ECs regulate apo A-I gene expression directly, the effect of the obesity-associated ECs anandamide and 2-arachidonylglycerol on apo A-I gene expression was examined in the hepatocyte cell line HepG2 and the intestinal cell line Caco-2. Apo A-I protein secretion was suppressed nearly 50% by anandamide and 2-arachidonoylglycerol in a dose-dependent manner in both cell lines. Anandamide treatment suppressed both apo A-I mRNA and apo A-I gene promoter activity in both cell lines. Studies using apo A-I promoter deletion constructs indicated that repression of apo A-I promoter activity by anandamide requires a previously identified nuclear receptor binding site designated as site A. Furthermore, anandamide-treatment inhibited protein-DNA complex formation with the site A probe. Exogenous over expression of cannabinoid receptor 1 (CBR1) in HepG2 cells suppressed apo A-I promoter activity, while in Caco-2 cells, exogenous expression of both CBR1 and CBR2 could repress apo A-I promoter activity. The suppressive effect of anandamide on apo A-I promoter activity in Hep G2 cells could be inhibited by CBR1 antagonist AM251 but not by AM630, a selective and potent CBR2 inhibitor. These results indicate that ECs directly suppress apo A-I gene expression in both hepatocytes and intestinal cells, contributing to the decrease in serum HDLc in obese individuals.

Body mass index and some biochemical parameters among valproate treated male epileptic patients

Objective: To assess the effect of continuous valproate monotherapy (VPA) on body mass index (BMI), serum leptin, malondialdehyde (MDA) and lipid profile in male epileptic children and adult patients in comparison to healthy male controls. Subjects, materials and methods: A case-control study design was adopted. Samples from 44 male patients (22 less than 18 years old, and 22 over than 18 years old), with primary generalized epilepsy, on continuous VPA monotherapy, for at least six months before participation in the study, were collected over the period from October 2009 to March 2010. Forty-four apparently healthy male volunteers (22 less than 18 years old, and 22 over than 18 years old) without previous history of epilepsy were recruited as controls. Serum levels of leptin, and lipid profile indices were estimated using commercially available kits and a manually prepared reagent for MDA assay. (BMI) was calculated as weight in kilograms divided by the squared height in meters. Results: The results revealed that epileptic children and epileptic adults receiving continuous VPA monotherapy had a significantly higher BMI (p<0.001), serum leptin, serum MDA and atherogenic index (AI) and a significantly lower (p<0.001) serum high density lipoprotein cholesterol (HDL-c) as compared to their matched control subjects. The results also revealed insignificant difference in serum total cholesterol (TC), triglycerides (TGs) and low density lipoprotein cholesterol (LDL-c) between epileptic children and epileptic adults on VPA and their matched control subjects. Serum leptin was positively correlated with body mass index standard deviation score (BMI SDS) of epileptic children (r=0.542; P<0.001) and duration of using VPA (r=0.215; P<0.001) in epileptic children. The results showed insignificant difference in serum TC, TGs and LDL-c between epileptic adults on VPA and control subjects. This study also revealed that the increase in serum leptin was significantly higher (p<0.001) in epileptic adults receiving continuous VPA monotherapy than in epileptic children. Conclusion: Continuous VPA monotherapy was associated with higher BMI and serum leptin and an increase in the oxidative stress marker MDA in both male epileptic children and adults. There was no effect of VPA use on lipid profile indices in both epileptic children and adults except significant decrease in serum HDL-c and significant increase in AI.

High Prevalence of Low High-Density Lipoprotein Cholesterol Concentrations and Other Dyslipidemic Phenotypes in an Iranian Population

This study was designed to determine the prevalence of different atherogenic dyslipidemic phenotypes, especially decreased serum high-density lipoprotein cholesterol (HDL-C) in an Iranian population and its relationship to other coronary artery disease (CAD) risk factor. The prevalence of lipid abnormalities was assessed in 2941 people, including 1396 males and 1545 females, aged more than 20 years. The population is representative of Iranian urban adults living in northwestern Iran. In addition to isolated forms of hypertriglyceridemia, hypercholesterolemia, and hypoalphalipoproteinemia, some dyslipidemic phenotypes including hypertriglyceridemia/low high-density lipoprotein (HDL) combination, mixed dyslipidemias, and severe dyslipidemias were assessed. The most prevalent abnormality was low HDL cholesterol (HDL-C; 73% including 63% for men and 93.3% for women). Hypertriglyceridemia (>150 mg/dL) was the second most prevalent abnormality (40.6%). Increased total cholesterol (>200 mg/dL) was observed in 35.4% of the subjects. The combination of hypertriglyceridemia and low HDL-C was observed in 9.9% of the population. Fifty eight percent of the low HDL-C cases were not accompanied with hypertriglyceridemia, and 24.4% of hypertriglyceridemic subjects had low HDL-C. Among subjects younger than 30 years, 19% had hypercholesterolemia, 13% had isolated low HDL-C less than 35 mg/dL, and 63% had HDL-C less than 40 mg/dL. Unexpectedly, except for the hypertriglyceridemia/low HDL-C pattern, which was more common in males, the other abnormal lipid profiles were more common in females. The prevalence of dyslipidemia, especially low HDL cholesterol, in Iranian adults is very high. Urgent preventive programs and changes in lifestyle are needed in this area.

Paradoxical HDL‐C reduction during rosiglitazone and fibrate treatment

Dyslipidaemia in Type 2 diabetes mellitus (T2DM) is one of the major contributors in the pathogenesis of atherosclerosis. Thiazolidinediones (TZD), a class of drugs used in the treatment of T2DM, also modify lipids, especially lowering serum triglycerides and raising high-density lipoprotein cholesterol (HDL-C). We describe five patients taking rosiglitazone and a fibrate who showed a paradoxical fall in HDL-C, which would have been missed if HDL-C had not been routinely monitored. This could have had a major impact in increasing the cardiovascular risk in these patients. Our five patients showed marked variation in both the decrease in serum HDL-C (50-89%) and also in the time taken for recovery of HDL-C after withdrawal of rosiglitazone (between 5 and 20 weeks). Apolipoprotein A1 mirrored the drop in HDL-C in four of the five patients but in one subject this was not seen, suggesting the possibility of multiple mechanisms leading to the phenomenon described, perhaps involving HDL metabolism. Improvements in glycaemic control with rosiglitazone (absolute HbA(1c) reduction between 0.6 and 3.0%) were seen in four of our patients. This suggests that the peroxisomal proliferator-activated receptor gamma signalling pathways relevant to glucose homeostasis were intact. As atherosclerosis is associated with a decrease in the HDL-C level, our observations reinforce the message that HDL-C should be measured before and after the commencement of rosiglitazone and also on increasing the dosage