Plasma lipids and apolipoproteins A and B in human pregnancy

A cross sectional study was carried out in 200 normal pregnant women between 8-40th weeks of gestation, 25 women during delivery and 25 women 6 weeks after delivery. Plasma and lipoprotein lipids were measured using standard procedures. Apolipoprotein A (Apo A) and Apolipoprotein B (Apo B), were measured by electroimmunoassay. Plasma levels of Apo A were elevated in pregnant women but the elevations were not significant until 17-20 weeks of gestation. Apo A during pregnancy was significantly correlated (p less than 0.001) with high density lipoprotein cholesterol (HDL-C). The level of Apo B increased progressively during pregnancy and it was significantly correlated (p less than 0.001) with total cholesterol (TC), plasma triglycerides (TG) and phospholipids (PL). Apo A and Apo B levels returned to non pregnant values within the puerperium, whereas TC, TG and PL remained significantly elevated above controls (p less than 0.01) 6 weeks post partum.     

Apolipoprotein E genotypes and metabolic risk factors for coronary heart disease in middle-aged women

Apo E genotypes and plasma metabolic risk factors (total cholesterol, triglycerides, HDL and LDL cholesterol, total/HDL cholesterol ratio, lipoprotein Lp (a), apolipoprotein A-I, A-II, apo B, and apo E) were determined in 134 healthy middle-aged (X +/- SD 49.62 +/- 4.83) women. The aim of this study was to investigate metabolic risk markers according to various apo E genotypes, and to evaluate a possible risk for coronary heart disease. The results revealed that the frequencies of apo E3/3 are the most frequent (46%), followed by E4/4 (2%), E3/4 (14%), E2/3 (14%), and E2/4 (2%) in the middle-aged women. Higher mean triglycerides, LDL-C and apo B levels were found with apo E3/4, and lower mean levels of HDL-C i.e. apo A-I than in other analyzed genotypes. Greater mean of total/HDL ratio and lower levels of apo A-II were seen with E2/4. Serum lipoprotein Lp (a) concentration was higher in women with genotypes E3/3. Apo E concentration was the lowest with genotypes E4/4, i.e. the highest with E2/3. Serum total cholesterol tended to be higher in women with genotypes E4/4. Genotype E3/4 is connected with the highest concentrations of (X +/- SD) triglycerides (1.74 +/- 0.78), LDL (4.28 +/- 1.88), apo B (1.03 +/- 0.32) and with the lowest concentrations of HDL cholesterol (1.11 +/- 0.21) in the relation to the other analyzed genotypes. This group of women could possibly represent high risk women for CHD. Genotype E3/3 is associated with the highest concentration of independent genetic risk marker for CHD, lipoprotein Lp (a) (0.19 +/- 0.27). The genotype E4/4 has the highest concentration of total cholesterol (5.93 +/- 1.01), and has to be taken in account for risk evaluation in women. High level of apo E (0.11 +/- 0.05) and low level of apo A-I (1.80 +/- 0.44) were associated with E2/3 genotypes. The significance of E3/4 with the high total/HDL ratio (5.52 +/- 2.21) and low apo A-II (0.53 +/- 0.09) is important indicator, because total/HDL cholesterol ratio represents independent Established Risk Factor (ERF) for CHD. Apolipoprotein E genotypes as genetic markers and investigation of serum metabolic risk markers appear to be important in view for further evaluation of high risk women for CHD in our population.     

Persistence of an atherogenic lipid profile after treatment of acute infection with brucella

Serum lipid changes during infection may be associated with atherogenesis. No data are available on the effect of Brucellosis on lipids. Lipid parameters were determined in 28 patients with Brucellosis on admission and 4 months following treatment and were compared with 24 matched controls. Fasting levels of total cholesterol (TC), HDL-cholesterol (HDL-C), triglycerides, apolipoproteins (Apo) A, B, E CII, and CIII, and oxidized LDL (oxLDL) were measured. Activities of serum cholesterol ester transfer protein (CETP), paraoxonase 1 (PON1), and lipoprotein-associated phospholipase A₂ (Lp-PLA₂) and levels of cytokines [interleukins (IL)-1β, IL-6, and tumor necrosis factor (TNFa)] were also determined. On admission, patients compared with controls had 1) lower levels of TC, HDL-C, LDL-cholesterol (LDL-C), ApoB, ApoAI, and ApoCIII and higher LDL-C/HDL-C and ApoB/ApoAI ratios; 2) higher levels of IL-1b, IL-6, and TNFa; 3) similar ApoCII and oxLDL levels and Lp-PLA₂ activity, lower PON1, and higher CETP activity; and 4) higher small dense LDL-C concentration. Four months later, increases in TC, HDL-C, LDL-C, ApoB, ApoAI, and ApoCIII levels, ApoB/ApoAI ratio, and PON1 activity were noticed compared with baseline, whereas CETP activity decreased. LDL-C/HDL-C ratio, ApoCII, and oxLDL levels, Lp-PLA₂ activity, and small dense LDL-C concentration were not altered. Brucella infection is associated with an atherogenic lipid profile that is not fully restored 4 months following treatment.     

Plasma levels of lipids and apoprotein in a group of middle-school students 11-14 years of age: preliminary data]

Plasma lipids and apoprotein A and B levels were measured in 63 children, of both sexes, in the age range 11-14 years. The children have been subjected to a blood drawing after a 12 hour fast at least. Statistical analysis proves that total cholesterol (TC) is positively correlated with triglycerides (TG), HDL cholesterol (HDL) with apolipoproteins A (Apo A), apolipoproteins A (Apo A) with apoproteins B (Apo B). In the end we confirm the utility of determining plasma lipids and apoproteins to estimate lipidic risk for atherosclerosis in pediatric age.     

Association between Lipid Ratios and Insulin Resistance in a Chinese Population

Aim

To explore the association of lipid ratios and triglyceride (TG) with insulin resistance (IR) in a Chinese population. We also provide the clinical utility of lipid ratios to identify men and women with IR.

Methods

This cross-sectional study included 614 men and 1055 women without diabetes. Insulin resistance was defined by homeostatic model assessment of IR > 2.69. Lipid ratios included the TG/ high density lipoprotein cholesterol (HDL-C), the total cholesterol (TC)/HDL-C and the low density lipoprotein cholesterol (LDL-C)/HDL –C. Logistic regression models and accurate estimates of the area under the receiver operating characteristic (AUROC) curves were obtained.

Results

In normal-weight men, none of lipid ratios nor TG was associated with IR. In overweight/obese men, normal-weight women and overweight/obese women, the TG/HDL-C, the TC/HDL-C and TG were significantly associated with IR, and the associations were independent of waist circumference. All of the AUROCs for the TG/HDL-C and TG were > 0.7. The AUROCs for TC/HDL-C ratio were 0.69–0.77. The optimal cut-offs for TG/HDL-C were 1.51 in men and 0.84 in women. The optimal cut-offs for TG were 1.78 mmol/L in men and 1.49 mmol/L in women, respectively. In men, the optimal cut-off for LDL-C/HDL-C is 3.80. In women, the optimal cut-off for LDL-C/HDL-C is 3.82.

Conclusion

The TG/HDL-C, the TC/HDL-C and TG are associated with IR in overweight/obese men, normal-weight and overweight/obese women. The LDL-C/HDL-C is only associated with IR in normal-weight women. The TG/HDL-C and TG might be used as surrogate markers for assessing IR.     

Gender differences in plasma levels of lipoprotein (a) in patients with angiographically proven coronary artery disease

The objective of the study was to assess the association between plasma levels of lipoprotein(a) [Lp(a)] and the presence of angiographically defined coronary artery disease (aCAD). Patients (346 men and 184 women) undergoing selective coronary angiography (SCA) were classified into groups with positive [aCAD(+)] and negative [aCAD(-)] findings and their age, body mass index (BMI), waist circumference, blood pressure, smoking, plasma total, LDL-, HDL-cholesterol (TC, LDL-C, HDL-C), triglycerides (TG), apolipoprotein B (apoB), Log(TG/HDL-C) and TC/HDL-C were determined. Concentration of plasma Lp(a) was estimated using the commercial solid phase two-side immunoradiometric assay of apolipoprotein apo(a). The plasma Lp(a) was significantly higher in both women and men with aCAD(+) compared to those with aCAD(-). While there was no significant difference in the Lp(a) level between men and women with aCAD(-) (median 138 vs. 145 units/l), the women with aCAD(+) had almost twice as high Lp(a) levels as men (median 442 vs. 274 units/l, p<0.001). Women with aCAD(+) had also significantly lower HDL cholesterol levels (1.09 vs. 1.20 mmol/l, p<0.05), higher triglycerides (1.82 vs. 1.46 mmol/l, p<0.05) and Log(TG/HDL-C) than women with aCAD(-). The differences in Lp(a) between positive and negative findings remained highly significant (p<0.001 in women, p<0.05 in men) after the adjustment for age, plasma HDL- and LDL-cholesterol and triglycerides in logistic regression analyses. In logistic regression model the Lp(a) and Log(TG/HDL-C) and smoking in women but smoking and age in men were the most powerful predictors of positive aCAD findings. Our findings suggest that Lp(a) is more strongly associated with aCAD+ in women than in men.     

Carbohydrate intake is correlated with biomarkers for coronary heart disease in a population of overweight premenopausal women

The associations between macronutrient intake and plasma parameters associated with increased risk for coronary heart disease (CHD) were evaluated in 80 overweight premenopausal women. We hypothesized that higher carbohydrate intake would be associated with a more detrimental plasma lipid profile. Dietary data were collected using a validated food frequency questionnaire (FFQ). Plasma total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were determined from two fasting blood samples. In addition, selected apolipoproteins (apo) and LDL peak size were measured. Values for TC, TG and HDL were not in the range of risk classification; however, the mean values of LDL-C, 2.7 +/- 0.7 mmol/L, were higher than the current recommendations. Carbohydrate intake was positively associated with TG and apo C-III (P < .01) concentrations, and negatively associated with LDL diameter (P < .01). Participants were divided into low (<53% of energy) or high (> or = 53% energy) carbohydrate intake groups. Individuals in the <53% carbohydrate group consumed more cholesterol and total fat, but also had higher intake of polyunsaturated and monounsaturated fatty acids (SFAs). In contrast, subjects in the > or =53% group consumed higher concentrations of glucose and fructose than those in the low-carbohydrate (LC) group. In addition, subjects consuming <53% carbohydrate had lower concentrations of LDL-C and apo B (P < .01) and a larger LDL diameter (P < .05) than the > or =53% group. These results suggest that the lower LDL-C in the LC group may be related to both the amount of carbohydrate and the type of fatty acids consumed by these subjects.     

有氧运动对高胆固醇血症大鼠肝脏低密度脂蛋白受体活性调节…

本文研究了实验性在醇血症大鼠肝脏低密度脂蛋白受体（ＬＤＬ－Ｒ）活性变化及有氧运动时ＬＤＬ－Ｒ活性调节的影响,发现,高脂（ＨＣ）组肝组织匀浆ＬＤＬ－ＲＩ自古以来生较正常对照（ＮＣ）组降低３７％（Ｐ〈０．０５）,同时血清大醇（ＴＣ）、低密度脂收白胆固醇（ＬＤＬ－Ｃ）及血清栽脂蛋白Ｂ（ＡｐｏＢ）均显著高于ＮＣ组（Ｐ〈０．０１）;高脂＋运动（ＨＥ）组ＴＣ、ＬＤＬ－Ｃ及ＡｐｏＢ均明显低于ＨＣ组,而ＬＤＬ－Ｒ     

Evaluation of endothelial dysfunction, lipid metabolism in women with polycystic ovary syndrome: relationship of paraoxonase 1 activity, malondialdehyde levels, low-density lipoprotein subfractions, and endothelial dysfunction

The aim of this study was to assess relationship of insulin resistance, oxidant-antioxidant status, endothelial dysfunction, lipid metabolism, and their contribution to the risks of cardiovascular disease in women with polycystic ovary syndrome (PCOS). Forty-five women with PCOS and 17 healthy women were included in this study. Nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA), Apo A1, Apo B, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride, small, dense LDL cholesterol (sdLDL-C), large buoyant LDL cholesterol (LbLDL-C) levels, and paraoxonase 1 (PON1) activity were measured in serum/plasma obtained from study groups. Insulin resistance [homeostasis model assessment (HOMA) index] and serum sex hormone binding globulin (SHBG), total testosterone (tT), free testosterone (fT), androstenedione, and dehydroepiandrosteronsulfate (DHEAS) levels were also evaluated. Significantly decreased SHBG, NO, HDL-C levels, and PON1 activities, but increased tT, fT, androstenedione, DHEAS, HOMA index, MDA, ET-1, LDL-C, sdLDL-C, and LbLDL-C values were found in PCOS patients compared with those of controls. There was a positive correlation between MDA and fT levels; and a negative correlation between PON1 activity and fT. Our data show that insulin resistance, dyslipidemia, endothelial dysfunction, and oxidative stress might contribute to the excess risk of cardiovascular disease reported in PCOS patients.     

Night work is associated with glycemic levels and anthropometric alterations preceding diabetes: Baseline results from ELSA-Brasil

Night work has been suggested as a risk factor for diabetes. Individuals with high triglyceride levels, high LDL cholesterol, low HDL cholesterol and obesity, especially abdominal obesity, have a greater chance of developing diabetes. The aim of this study was to analyze glycemic levels, total cholesterol, HDL-C, LDL-C, triglycerides and the anthropometric alterations that precede diabetes, considering their possible association with nigh work among a non-diabetic population. Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) comprises of 15,105 civil servants (35–74 years old) at baseline (2008–2010). The following parameters were analyzed: serum cholesterol (total cholesterol, HDL-C, LDL-C), triglycerides and glucose drawn from 12-hour fasting blood sample, glycated hemoglobin and 2-hour plasma glucose obtained after a 75 g oral glucose tolerance test, BMI, hip and waist measurements using standard equipment and techniques. Participants with diabetes, retired workers and day workers with previous experience of night work were excluded. Generalized linear models, a gamma regression model with an identity link function, were performed to test the association of night work with metabolic and anthropometric variables. The study sample consisted of 3918 men and 4935 women; 305 (7.8%) and 379 (7.7%) of the participants were men and women who worked at night, respectively. Among the men, the exposure to night work was associated with an increase in BMI (b-value = 0.542; p = 0.032) and waist circumference (b-value = 1.66; p = 0.014). For women, increased fasting plasma glucose (b-value = 2.278; p < 0.001), glycated hemoglobin (b-value = 0.099, p < 0.001) and 2 hour plasma glucose (b-value = 5.479, p = 0.001) were associated with night work after adjustments. No significant associations between night work and triglycerides, LDL-C, HDL-C, total cholesterol levels or waist–hip ratio were found. The influences of night work on metabolic and anthropometric factors suggest night work as a potential risk factor for type 2 diabetes. Further studies are needed to investigate the inconclusive data on gender differences in the associations.     

Effects of conjugated equine estrogen and medroxyprogesterone acetate on lipoprotein(a) and other lipoproteins in japanese postmenopausal women with and without dyslipidemia

BACKGROUND/AIM: The cardiovascular effects of postmenopausal hormone replacement are controversially discussed. We investigated the effects of 12 months of treatment with conjugated equine estrogen and medroxyprogesterone acetate on lipoprotein(a) [Lp(a)] and other lipoproteins in Japanese postmenopausal women (PMW) with and without dyslipidemia. METHODS: Forty-three normolipidemic and 17 dyslipidemic PMW [total cholesterol (TC) >/=220 mg/dl or triglyceride (TG) >/=150 mg/dl] received conjugated equine estrogen (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) daily for 12 months, and the results were compared with those of 26 normolipidemic and 14 dyslipidemic subjects declining this treatment as controls. The fasting serum levels of Lp(a), TC, TG, high-density lipoprotein cholesterol, low- density lipoprotein cholesterol, apolipoprotein (Apo) AI, Apo AII, Apo B, Apo CII, and Apo E were measured in each subject at baseline and 12 months after this treatment initiation. RESULTS: The treatment decreased Lp(a) similarly in normolipidemic and dyslipidemic PMW and decreased TC, low-density lipoprotein cholesterol, Apo CII, and Apo E and increased high-density lipoprotein cholesterol, Apo AI, and Apo AII in both groups. The therapy also significantly increased TG in normolipidemic but not dyslipidemic subjects. In controls, the levels of Lp(a) and other lipoproteins were unaltered. CONCLUSIONS: In PMW with or without dyslipidemia, improvement in Lp(a) and other lipoproteins may represent cardiovascular benefits of hormone replacement therapy. However, an elevation of the TG levels seen with the therapy warrants caution, especially in PMW without dyslipidemia.     

Assessment of gender-related differences in vitamin D levels and cardiovascular risk factors in Saudi patients with type 2 diabetes mellitus

Diabetes is a major risk factor for cardiovascular disease (CVD) including stroke, coronary heart disease, and peripheral artery disease. It remains a leading cause of mortality throughout the world, affecting both women and men. This investigation was aimed to study gender based differences in cardiovascular risk factors of adult population with type-2 diabetes mellitus (T2DM) and to check the correlation between serum HbA1C, lipid profile and serum vitamin D levels, in T2DM patients of Riyadh, Saudi Arabia. This hospital-based cross-sectional study involving subjects was divided into two gender based groups; normal male (800), diabetic male (800) and normal female (800) and T2DM females (800). Blood samples were analyzed for fasting glucose (FBG), HbA1c, total cholesterol (TC), triglycerides (Tg), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and serum levels of 25(OH)-vitamin D in all groups. All the glycemic control parameters and lipid profile parameters were found to be significantly different in diabetic vs non-diabetic group (p < 0.001) in both genders. The results also show that vitamin D concentration decreased significantly (p < 0.001) in diabetic patients than the healthy individuals in both the genders. Vitamin-D and HbA1C were negatively correlated in both males and females in T2DM patients and significant at P < 0.05. Our study reveals that dyslipidemia remains one of the major risk factors of CVD in T2DM. In addition to dyslipidemia, decreased levels of vitamin-D associated with increased HbA1C alarms the early diagnosis of Type 2 Diabetes.     

Genetic loci for blood lipid levels identified by linkage and association analyses in Caribbean Hispanics

To identify genetic loci influencing blood lipid levels in Caribbean Hispanics, we first conducted a genome-wide linkage scan in 1,211 subjects from 100 Dominican families on five lipid quantitative traits: total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), and LDL-C/HDL-C ratio. We then investigated the association between blood lipid levels and 21,361 single nucleotide polymorphisms (SNP) under the 1-logarithm of odds (LOD) unit down regions of linkage peaks in an independent community-based subcohort (N = 814, 42% Dominican) from the Northern Manhattan Study (NOMAS). We found significant linkage evidence for LDL-C/HDL-C on 7p12 (multipoint LOD = 3.91) and for TC on 16q23 (LOD = 3.35). In addition, we identified suggestive linkage evidence of LOD > 2.0 on 15q23 for TG, 16q23 for LDL-C, 19q12 for TC and LDL-C, and 20p12 for LDL-C. In the association analysis of the linkage peaks, we found that seven SNPs near FLJ45974 were associated with LDL-C/HDL-C with a nominal P < 3.5 × 10(-5), in addition to associations (P < 0.0001) for other lipid traits with SNPs in or near CDH13, SUMF2, TLE3, FAH, ARNT2, TSHZ3, ZNF343, RPL7AL2, and TMC3. Further studies are warranted to perform in-depth investigations of functional genetic variants in these regions.     

Lipoprotein lipase and apoE polymorphisms: relationship to hypertriglyceridemia during pregnancy.

Pregnancy is associated with increases in plasma total cholesterol (TC) and triglycerides (TG). Individuals with decreased LPL activity have a mild form of hypertriglyceridemia. Variations in the apolipoprotein E (apoE) gene have been associated with increases in plasma TG in addition to differences in plasma TC, LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C). Because of the overproduction of TG-rich VLDL, normal pregnancy challenges the lipolytic capacity of LPL and the clearance of remnants particles. During pregnancy, LPL and apoE polymorphisms may contribute to hypertriglyceridemia. This study investigated the impact of three LPL polymorphisms and the apoE genotypes on lipid levels during pregnancy. Fasting plasma lipids were measured and analyses of the LPL and apoE polymorphisms were performed in 250 women in the third trimester of pregnancy. S447X carriers had lower TG (P = 0.003), and N291S carriers had lower HDL-C (P < 0.02) and higher fractional esterification rate of HDL (FER(HDL)) (P = 0.007), a measure of HDL particle size, than the noncarriers. The E2 allele was associated with lower TC, LDL-C, and FER(HDL) (P < 0.05) compared to the E3/E3 genotype. These findings support that LPL and apoE polymorphisms play an important role in lipid metabolism in pregnancy. The relationship of these polymorphisms to risk of coronary heart disease in women requires further study.     

FT3/FT4比值、Apo B/Apo A1比值与急性缺血性脑卒中患者临床疗效和出院后短期预后的关系研究

摘要 目的：探讨游离三碘甲腺原氨酸（FT3）/游离甲状腺素（FT4）比值、载脂蛋白B （Apo B）/载脂蛋白A1（Apo A1）比值与急性缺血性脑卒中（AIS）患者临床疗效和出院后短期预后的关系。方法：选取2020年2月至2022年2月安徽省第二人民医院收治的102例AIS患者,所有患者入院后接受血运重建、抗血小板等治疗,根据临床疗效将患者分为有效组（76例）和无效组（26例）。治疗后检测所有AIS患者血清FT3、FT4、Apo B、Apo A1水平,计算FT3/FT4比值、Apo B/Apo A1比值,所有AIS患者出院后随访3个月,根据AIS患者随访期间的预后情况将其分为预后不良组（31例）和预后良好组（71例）。比较不同组间血清FT3、FT4、Apo B、Apo A1水平以及FT3/FT4比值、Apo B/Apo A1比值差异,分析影响AIS患者出院后短期预后的因素。结果：无效组血清FT3水平、FT3/FT4比值低于有效组（P＜0.05）,血清Apo B水平、Apo B/Apo A1比值高于有效组（P＜0.05）。预后不良组血清FT3水平、FT3/FT4比值低于预后良好组（P＜0.05）,血清Apo B水平、Apo B/Apo A1比值高于预后良好组（P＜0.05）。美国国立卫生院神经功能缺损评分（NIHSS评分）高、Apo B/ApoA1比值增高是AIS患者出院后短期预后不良的危险因素（P＜0.05）,FT3/FT4比值增高是其保护因素（P＜0.05）。结论：AIS临床治疗无效和预后不良患者FT3/ FT4比值降低,Apo B/ApoA1比值增高,低FT3/ FT4比值和高Apo B/ApoA1比值与AIS患者出院后短期预后不良有关。     

Maternal serum lipids during pregnancy and infant birth weight: the influence of prepregnancy BMI

Maternal obesity may be associated with metabolic factors that affect the intrauterine environment, fetal growth, and the offspring's long-term risk for chronic disease. Among these factors, maternal serum lipids play a particularly important role. Our objective was to estimate the influence of variation in maternal serum lipid levels on variation in infant birth weight (BW) in overweight/obese and normal weight women. In a prospective cohort of 143 gravidas, we measured maternal serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) at 6-10, 10-14, 16-20, 22-26, and 32-36 weeks gestation. Effects of maternal serum lipid levels on infant BW adjusted for gestational age at delivery (aBW) were analyzed using linear regression models. In analyses stratified by maternal prepregnancy BMI categorized as normal (≤25.0 kg/m(2)) and overweight/obese (>25.0 kg/m(2)), we found a significant (P < 0.05) inverse association between aBW and HDL-C at all time points starting at 10 weeks gestation in overweight/obese women. No significant effect was found in normal weight women. In contrast, increased maternal serum TG was significantly associated with increased aBW only for normal weight women at 10-14 and 22-26 weeks gestation. Variation in aBW is not associated with variation in maternal serum TC or LDL-C for either stratum at any time point. We postulate that such differences may be involved in the "physiological programming" that influences later risk of chronic disease in the infants of overweight/obese mothers.     

Serum zinc in healthy Belgian children

Many reports mention marginal zinc status in childhood. Information on serum zinc (Zn) in Belgian children since the last reports are old and feeding habits are changing. Four hundred fifty-seven healthy children (0-14 yr, 262 boys) had a venipuncture after an overnight fast during a vaccination campaign. Serum Zn, alpha-tocopherol (alpha-T), cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (Apo B), Apo A, and malondialdehyde (MDA) were determinated. The median Zn value is lower in infants than in older children (respectively 11.6 micromol/L vs 12.8 micromol/L). The type of infant feeding does not influence the serum Zn concentrations (breast-feeding, adapted, hypoallergenic, soy, or thickened). No children had increased serum MDA concentrations and the value is not influenced by the Zn concentration. Children presenting higher serum Zn values also have significantly higher serum alpha-T levels. In infants, there is a significant positive correlation between serum Zn and cholesterol, LDL-C, and Apo B. In this apparently healthy population, no signs of abnormal in vivo peroxidation of fatty acids are observed, even in the children with low serum Zn. More sensitive methods for the detection of peroxidation are necessary for determination of in vivo effects of marginal trace element status.     

Apo E gene polymorphism on development of diabetic nephropathy

Type 2 diabetes causes premature morbidity and mortality due to the complications of atherosclerosis and diabetic nephropathy (DN). Polymorphism of Apo E gene is known to influence lipid metabolism. Apo E is polymorphic, consisting of three common isoforms (epsilon2, epsilon3 and epsilon4) encoded by three alleles (2, 3 and 4) in exon 4 on chromosome 19. The aim of this study was to investigate the effect of Apo E polymorphism as a prognostic risk factor for the development of DN. A total of 108 NIDDM patients were recruited from the Nephrology and Endocrinology Departments of our hospital. All subjects were divided into three groups: Group I: diabetes with nephropathy (n:37), group II: diabetes without nephropathy (n:71), group III: controls (n:46). Apo E genotypes were determined by real-time PCR. The epsilon4 allele frequency was significantly higher in-group I (10.8%) than in-group III (2.2%), (p < 0.05). In diabetics without nephropathy, the total cholesterol and LDL cholesterol levels were significantly lower in subjects with epsilon2 alleles than epsilon3 and epsilon4 alleles. In conclusion, the present prospective study indicates that the epsilon4 allele of the Apo E polymorphism is one of the prognostic risk factors involved in the development of DN with type 2 diabetes mellitus.     

Hyperexpression of N-acetylglucosaminyltransferase-III in liver tissues of transgenic mice causes fatty body and obesity through severe accumulation of Apo A-I and Apo B

N-Acetylglucosaminyltransferase (GnT)-III catalyzes the attachment of an N-acetylglucosamine (GlcNAc) residue to mannose in beta(1-4) configuration in the region of N-glycans and forms a bisecting GlcNAc. To investigate the pathophysiological role of dysregulated glycosylation mediated by aberrantly expressed GnT-III, we generated transgenic mice hyperexpressing the human GnT-III in the liver by introducing human GnT-III cDNA under the control of mouse albumin enhancer/promoter. Total five transgenic founder mice (pGnTSVTpA-10, -14, -20, -25, and -51) expressed the human GnT-III in their livers and were characterized by molecular genetic means. The copy number of transgene integrated into the genome of these mice ranged between 1 and 3 copies per haploid genome. Northern and Western blot analyses showed that the transgene is specifically expressed in the liver but not in any other tissues tested. The triglyceride level in GnT-III transgenic mice was significantly decreased, however, no significant differences in the levels of glucose, cholesterol, or albumin were observed between transgenic and nontransgenic mice. Although glutamate oxaloacetic transaminase and glutamic pyruvic transaminase activities of transgenic mice were also higher than those of nontransgenic mice, no differences in total bililubin and total protein were observed between the two animal lines. Large amounts of apolipoprotein (Apo) A-I and Apo B were specifically detected in the intracellular liver of transgenic mice. The accumulation of Apo A-I in hepatocytes may be due to aberrant glycosylation, since glycosylated Apo A-I was not observed in transgenic mice. However, the accumulated Apo B was severely glycosylated. Therefore, it is suggested that highly expressed transgenic GnT-III allowed unknown target proteins to be glycosylated in large amounts, and the resulting target protein(s) disrupted in assembly formation of Apo A-I in the hepatocytes and cause a decrease in the release of lipoproteins and accumulations of Apo A-I and Apo B in the liver. The transgenic mice showed aberrant glycosylation by GnT-III, resulting in numerous lipid droplets in liver tissues and the obesity. These mice showed microvesicular fatty changes with abnormal lipid accumulation in the hepatocytes. Our study provides the basis for future analysis of the role of glycosylation in hepatic pathogenesis. In the transgenic mice, Apo A-I and Apo B were significantly increased compared with levels in nontransgenic liver tissues.     

Colesevelam Hydrochloride-Ezetimibe Combination Lipid-Lowering Therapy in Patients with Diabetes or Metabolic Syndrome and a History of Statin Intolerance

ObjectiveTo determine the effectiveness and safety of colesevelam hydrochloride (HCl) and ezetimibe combination therapy in statin-intolerant patients with dyslipidemia and diabetes mellitus (DM) or metabolic syndrome (MS).MethodsWe identified potential study subjects through a computerized text search of patient electronic medical records using the terms colesevelam, WelChol, ezetimibe, and Zetia. Medical records were subsequently reviewed to identify all patients with DM or MS. Baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglyceride levels immediately before the initiation of therapy with colesevelam HCl (1.875 g twice a day) or ezetimibe (10 mg daily) were compared with those after a minimum of 3 months of single drug therapy and after a minimum of 3 months of combination therapy. Drug safety was evaluated by review of transaminase levels and reports of side effects or drug discontinuation.ResultsThe computerized search initially identified 91 electronic medical records; 16 patients fulfilled all study criteria. Baseline patient demographics included a mean age of 62.5 (± 11.8) years and a mean body mass index of 31.4 (± 5.2) kg/m²; 50% of patients were female, 75% had type 2 DM, and 25% had MS. In comparison with baseline, colesevelam HCl-ezetimibe combination therapy was associated with significant reductions in mean levels of total cholesterol (27.5%), LDL-C (42.2%), and non-HDL-C (37.1%). In addition, 50% of patients achieved the National Cholesterol Education Program Adult Treatment Panel III LDL-C target of less than 100 mg/dL. Therapy was well tolerated, with no significant changes in mean transaminase levels, no reports of myalgia, and no discontinuation of therapy.ConclusionColesevelam HCl-ezetimibe combination therapy was associated with improved TC, LDL-C, and non-HDL-C lipid profiles and was well tolerated. Such therapy may be a reasonable consideration for statin-intolerant patients with DM or MS who have elevated cholesterol levels. (Endocr Pract. 2007;13:11-16)