A preponderance of small dense LDL is associated with specific insulin,proinsulin and the components of the insulin resistance syndrome in non-diabetic subjects

Summary Recently, the presence of small dense low density lipoprotein (LDL) has been postulated to be a stronger risk factor for coronary heart disease than large LDL. While small dense LDL has been associated with individual components of the insulin resistance syndrome such as hypertension, high triglyceride level, low high density (HDL) cholesterol, and diabetess mellitus, there has been little work exploring whether LDL size is decreased in subjects with multiple metabolic disorders. We examined the association of LDL size and pattern to specific insulin (which does not cross-react with proinsulin), proinsulin, increased triglyceride, decreased HDL, hypertension and impaired glucose tolerance in 488 non-diabetic subjects from the San Antonio Heart Study. LDL size was significantly related to specific insulin, proinsulin and the fasting proinsulin/insulin ratio. Small dense LDL was significantly associated with high triglyceride level, decreased HDL cholesterol, hypertension and impaired glucose tolerance. LDL size (å) decreased in a stepwise fashion with increasing number of the metabolic disorders described above (zero 262.6±9.4; one 257.0±9.3; two 256.4±9.4; three 249.0±9.1; and four 244.9±9.0). These results were similar in men and women and in non-Hispanic whites and Mexican Americans. The association between LDL size and the number of metabolic disorders remained statistically significant even after adjustment for obesity, body fat distribution, gender, ethnicity, proinsulin and insulin concentrations. Furthermore, decreases in LDL size are also significantly associated with both a selective beta-cell defect (as estimated by the fasting proinsulin/insulin ratio) and insulin resistance (as estimated by the fasting insulin concentrations) although the association was some-what stronger for the latter. We conclude that small dense LDL may form part of the insulin resistance syndrome in non-diabetic subjects.Abbreviations BMI Body mass index - LDL low density lipoprotein - HDL high density lipoprotein - IGT impaired glucose tolerance - NIDDM non-insulin-dependent diabetes mellitus - WHR waist-hip ratio     

Hepatitis C virus infection causes hypolipidemia regardless of hepatic damage or nutritional state: An epidemiological survey of a large Japanese cohort

Aim: Infection with hepatitis C virus (HCV) is the leading cause of liver cirrhosis that develops into hepatocellular carcinoma. Previous studies have shown in vitro that lipids within hepatocytes are crucially important for a series of HCV infection–proliferation–release processes. On the other hand, in the patients with HCV, the serum total cholesterol (Total‐C) and low‐density lipoprotein cholesterol (LDL‐C) levels have been reported to be lower. We conducted an epidemiological survey of a large cohort and investigated whether the lower serum lipid levels were caused by a direct or the secondary effects of HCV infection (i.e. hepatic damage or nutritional disorder). Methods: Among 146 857 participants (male, 34%; female, 66%) undergoing public health examinations between 2002 and 2007 in Ibaraki Prefecture, Japan, the HCV positive rates determined by HCV antibody/antigen and/or RNA tests were 1.37% and 0.67% in males and females, respectively. Results: In addition to Total‐C and LDL‐C, serum high‐density lipoprotein cholesterol and triglyceride concentrations were also significantly lower in the HCV positive subjects compared with the negative subjects, regardless of sex, age or nutritional state evaluated by body mass index. Multivariate analysis showed that HCV infection was the strongest among the factors to be significantly associated with the lower level of these lipids. Particularly, the hypolipidemia was also confirmed in the HCV positive subjects with normal aminotransferase levels (alanine aminotransferase ≤30 and aspartate aminotransferase ≤30). Conclusion: This epidemiological survey in a large Japanese cohort suggests that the HCV infection itself might directly cause hypolipidemia, irrespective of host factors including age, hepatic damage and nutritional state.     

The association of triglyceride and glucose index,and triglyceride to high‐density lipoprotein cholesterol ratio with prehypertension and hypertension in normoglycemic subjects: A large cross‐sectional population study

Insulin resistance (IR) plays an important role in the development of hypertension. Triglyceride and glucose index (TyG index), and triglyceride to high‐density lipoprotein cholesterol ratio (TG/HDL‐c) as effective IR surrogate indexes have been verified in numerous studies. Therefore, the authors conducted a large cross‐sectional study to explore the association of TyG index and TG/HDL‐c with prehypertension and hypertension in the same normoglycemic subjects from Tianjin, China. A total of 32 124 adults were eligible for this study. According to the level of blood pressure, the enrolled individuals were divided into three groups, which were normotension, prehypertension, and hypertension. In multiple logistic regression analysis, there was associated with prehypertension and hypertension when comparing the highest TyG index to the lowest TyG index and corresponding ORs were 1.795 (1.638, 1.968) and 2.439 (2.205, 2.698), respectively. For TG/HDL‐c, the corresponding ORs were 1.514 (1.382, 1.658) and 1.934 (1.751, 2.137), respectively. Furthermore, when comparing the fourth quartile to the first quartile of TyG index and TG/HDL‐c, respectively, both corresponding ORs of hypertension were higher than prehypertension. Elevated TyG index and TG/HDL‐c levels were associated with prehypertension and hypertension in normoglycemic individuals. Moreover, the TyG index was more significant than TG/HDL‐c in distinguishing hypertension. They have the potential to become cost‐effective monitors in the hierarchical management of prehypertension and hypertension.     

The effect of insulin resistance and obesity on low-density lipoprotein particle size in children

Objective: In adults, it was shown that obesity and insulin resistance affect low−density lipoprotein (LDL) particle size and small dense (sd) LDL is associated with cardiovascular diseases. In this study, we investigated the effect of obesity and insulin resistance on LDL particle size.Methods: Twenty−six obese children (13 girls, 13 boys) with a median age of 10.5 years and 27 healthy control subjects (17 girls, 10 boys) with a median age of 11.5 were enrolled in the study.Results: The number of patients with insulin resistance in the obese group was 15 out of 26. In the control group, there was no subject with insulin resistance. Serum triglyceride and very LDL (VLDL) levels were higher and serum high−density lipoprotein levels (HDL) were lower in the obese patients than in the controls. There was no statistical difference in the LDL particle size between the two groups (medians: 26.6 vs. 26.7 nm (p=0.575)). The size of LDL particle was not correlated with body mass index (BMI) standard deviation score (SDS), homeostasis model assessment of insulin resistance (HOMA−IR), or serum lipids.Conclusion: Measurement of LDL particle size as a routine procedure is not necessary in childhood obesity.Conflict of interest:None declared.     

极低密度脂蛋白与胰岛素抵抗患者的脂代谢紊乱

极低密度脂蛋白(VLDL)是机体转运内源性甘油三酯的主要形式,可分为大颗粒的VLDL1和小颗粒的VLDL2。VLDL血浓度升高是胰岛素抵抗(IR)脂代谢紊乱的主要特征,以VLDL1升高为主。其升高的机制与IR密切相关,包括:磷脂酰肌醇3激酶信号转导途径受损,固醇调节元件结合蛋白-C表达上调,游离脂肪酸大量内流,载脂蛋白(apo)B-100稳定性增加、肠内apoB-48水平升高,脂蛋白脂酶活性下降及低密度脂蛋白受体清除途径受损,导致VLDL生成过度、清除减弱,从而使其血浓度升高。     

Obesity, adipocytokines, and insulin resistance in breast cancer

The adipocytokines are biologically active polypeptides that are produced either exclusively or substantially by the adipocytes, and act by endocrine, paracrine, and autocrine mechanisms. Most have been associated with obesity, hyperinsulinaemia, type 2 diabetes, and chronic vascular disease; in addition, six adipocytokines--vascular endothelial growth factor, hepatocyte growth factor, leptin, tumour necrosis factor-alpha, heparin-binding epidermal growth factor-like growth factor, and interleukin-6--promote angiogenesis while one, adiponectin, is inhibitory. Obesity and insulin resistance have both been identified as risk factors for breast cancer and are associated with late-stage disease and poor prognosis. Angiogenesis is essential for breast cancer development and progression, and so it is plausible that obesity-related increases in adipocytokine production and a reduction in adiponectin may adversely affect breast cancer outcome by their angiogenesis-related activities. There is also experimental evidence that some adipocytokines can act directly on breast cancer cells to stimulate their proliferation and invasive capacity. Thus, adipocytokines may provide a biological mechanism by which obesity and insulin resistance are causally associated with breast cancer risk and poor prognosis. Both experimental and clinical studies are needed to develop this concept, and particularly in oestrogen-independent breast cancers where preventive and therapeutic options are limited.     

Inhibition of intestinal cholesterol absorption by surfomer (alpha-olefin maleic acid] affects hepatic cholesterol synthesis and low density lipoprotein transport in hamsters fed a fat-enriched diet

BACKGROUND: Surfomer (alpha-olefin maleic acid) reduces intestinal cholesterol absorption. AIMS: This study was performed to investigate the effect of surfomer on cholesterol synthesis and low density lipoprotein in hamsters fed a hypercholesterolaemic, lipid-enriched diet. ANIMALS AND METHODS: Male hamsters were fed a diet enriched in cholesterol (0.07%) and saturated fatty acids (coconut oil 20%); the diet was supplemented with 3% surfomer, for 1-4 weeks. Cholesterol synthesis was assessed measuring incorporation of [3H]water into tissue sterols; low density lipoprotein clearance was determined using a primed-continuous infusion of (125I)tyramine-cellobiose lipoprotein. RESULTS: Cholesterol synthesis was suppressed after 3 weeks of hyperlipidaemic diet in liver and small bowel (by 88% and 38%, respectively) and was significantly increased by supplementing the fat-enriched diet with surfomer. Low density lipoprotein-cholesterol was increased by 44% after 4 weeks of hyperlipidaemic diet, in parallel with a decrease in hepatic low density lipoprotein clearance rates (48+/-3 vs 68+/-7 microl of plasma/h per g of tissue). Concurrent treatment with surfomer for 1, 2 or 4 weeks prevented the decrease of clearance and maintained normal low density lipoprotein-cholesterol levels at all time points. CONCLUSIONS: Surfomer represents a powerful tool to investigate the impact of cholesterol absorption on sterol homeostasis. Furthermore, since surfomer appears to normalize low density lipoprotein transport in hamsters fed a diet comparable to a lipid-rich "western-style" regimen, this drug may deserve consideration as an adjunct treatment for hypercholesterolaemia in selected patient groups.     

吡格列酮对实验性动脉粥样硬化大鼠血脂水平的影响及临床意义

目的观察吡格列酮对高脂饮食诱导动脉粥样硬化模型大鼠血脂水平的影响,并探索其临床意义。方法设清洁型SD大鼠26只,随机分为对照组(n=9)、高脂饮食组(n=17),高脂饮食组喂养12周后再随机分为模型组(n=8)和吡格列酮组(n=9),分别给予蒸馏水、蒸馏水(1.5ml/100g)和吡格列酮10mg/(kg·d)灌胃,1次/d,同时继续高脂饮食,干预4周后,检测各组血脂水平并观察主动脉病理形态学改变。结果高脂饮食喂养12周后,与对照组相比,模型组和吡格列酮组三酰甘油(TG)、总胆固醇(TC)显著升高(P<0.01)。给药干预4周后,吡格列酮组干预后TG、TC、低密度脂蛋白胆固醇(LDL-C)较干预前明显降低(P<0.01),与模型组比较,吡格列酮组TG、TC水平明显降低(P<0.01)。且可减轻高脂饮食诱导的主动脉内膜增厚和平滑肌细胞增殖。结论吡格列酮可改善高脂血症大鼠血脂水平,延缓主动脉粥样硬化病理改变,提示吡格列酮的抗动脉粥样硬化作用可能部分归于血脂改善效应。     

每日与隔日服用阿托伐他汀降低血清低密度脂蛋白胆固醇与高敏C-反应蛋白浓度的疗效比较

目的比较每日与隔日口服阿托伐他汀（立普妥）20mg降低血清低密度脂蛋白胆固醇（10wdensitylipoproteincholester01．LDL-C）与高敏C-反应蛋白浓度的治疗效果。方法96例高脂血症患者,按电脑随机数字表法分为每天口服组48例与隔日口服组48例。两组每次服用阿托伐他汀20mg,检测治疗前与治疗后2个月患者LDL-C、总胆固醇与高敏C-反应蛋白浓度并进行比较。结果阿托伐他汀治疗2个月后,每天口服组与隔日口服组血清LDL-C浓度分别下降34．3％和35．1％,两组比较差异无统计学意义（P〉O．05）;而血清总胆固醇下降6．7％和4．3％,两组比较差异无统计学意义（P＞O．05）;血清高敏C-反应蛋白浓度下降17．9％和20．7％,两组比较差异无统计学意义（P〉O．05）。结论每日与隔日口服阿托伐他汀20mg降低血清LDL-C及高敏C-反应蛋白浓度效果相似．可节约药费．     

磁共振波谱技术测定中国人群血脂亚组分的初步探讨

目的:脂蛋白颗粒直径、各血脂亚组分是独立于低密度脂蛋白胆固醇(LDL-C)的动脉粥样硬化性心血管疾病(ASCVD)的危险因素。本研究采用磁共振波谱技术(nuclear magnetic resonance spectroscopy,NMRS)分析中国人群的血脂亚组分谱,建立NMRS检测中51个检测指标中国表观健康人群的正常参考范围。方法:本研究首先评估NMRS的稳定性,并在1091例中国人群中比较了NMRS与当前临床常规血脂检测共同指标的一致性。随后以其中691例健康人群数据,建立NMRS各项血脂指标正常参考区间,并进行性别亚组的差异分析。结果:NMRS血脂检测平台稳定性评估中,6项临床常规血脂指标(总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白A1、载脂蛋白B)批间变异系数为1.39%~2.62%,并与临床常规生化方法学检测结果之间具有高度相关性(6项指标相关系数介于0.927~0.978)。691例健康成人的低密度脂蛋白颗粒平均粒径为19.93~21.20 nm,极低密度脂蛋白、中密度脂蛋白、低密度脂蛋白的总颗粒数参考区间分别为32.6~347.3 nmol/L、8.5~105.8 nmol/L、626.0~1829.6 nmol/L。建立5个极低密度脂蛋白亚组分、6个低密度脂蛋白亚组分、4个高密度脂蛋白亚组分的总胆固醇和甘油三酯浓度的中国表观健康成人参考区间。性别亚组分析显示,不同血脂组分在男性与女性间差异具有统计学意义。结论:NMRS检测可获得更丰富的血脂亚类谱,并建立中国健康成人的血脂各亚组分参考区间,为NMRS在临床的广泛应用打下坚实基础。     

Japanese IGT subjects with high insulin response are far more frequently associated with the metabolic syndrome than those with low insulin response

Impaired glucose tolerance (IGT) represents a prediabetic state positioned somewhere between normal glucose tolerance and diabetes, which is also assumed to make individuals in this state highly susceptible to atherosclerotic disease. IGT also accounts for a highly heterogeneous population, with the condition varying from individual to individual. In this study, we stratified subjects with IGT by their insulin response and compare the pathology of IGT when it is associated with high or low insulin response to gain insight into the diverse pathology of IGT. Of the male corporate employees who underwent 75 g OGTT at the corporation's healthcare center, 150 individuals diagnosed with IGT (isolated IGT, combined IGT and IFG) comprised our study subjects. The study subjects were stratified into four quartiles by percentile AUC for insulin, and those in the 25th or less percentile were defined as the low insulin response group (n=37) vs those in the 76th or greater percentile defined as the high insulin response group (n=38), and these groups were compared. There was no significant difference observed between the two groups in regard to post-OGTT glucose response and area under the glucose curve. However, the high insulin response group was associated with higher BMI, subcutanesous fat area, uric acid levels, HOMA-β cell values, and Δinsulin/Δglucose (30 min) than the low insulin response group. The number of risk factors for the metabolic syndrome detected (as defined by the ATPIII diagnostic criteria) per subject was 2.84±0.17 and 2.08±0.20, respectively, in the high insulin response group and in the low insulin response group, with the number significantly (p<0.05) higher in the high insulin response group. Furthermore, the incidence of the metabolic syndrome as defined by the ATPIII diagnostic criteria was 63.2% (24/38) in the high insulin response group vs 32.4% (12/27) in the low insulin response group, with the incidence significantly (p<0.01) higher in the high insulin response group. Likewise, the incidence of the metabolic syndrome as defined by the Japanese diagnostic criteria was found to be significantly (p<0.05) higher in the high insulin response group at 50% (19/38) compared to 27.0% (10/37) in the low insulin response group. Our study findings suggest that IGT subjects with high insulin response and those with low insulin response vary greatly in regard to the number of atherosclerotic risk factors complicated and the frequency with which they are associated with the metabolic syndrome. It is also shown in middle-aged Japanese males that of the two forms of IGT, IGT with high insulin response is more closely linked to the pathogenesis of atherosclerotic cardiovascular disease.     

Increased turnover of very low density lipoprotein triglyceride during treatment with cholestyramine in familial hypercholesterolaemia

Kinetics of very low density lipoprotein (VLDL) triglyceride were determined in seven patients with heterozygous familial hypercholesterolaemia, using a 3H-glycerol technique. The study was repeated after 5-7 weeks of therapy with the bile acid-binding resin, cholestyramine. The rate of synthesis of VLDL triglyceride was increased by 85% (P less than 0.05) during resin therapy. Simultaneously, the fractional catabolic rate of VLDL was increased by 40% (P less than 0.02), so that only a moderate increase in plasma concentration was observed. Repeated measurements of VLDL size by electron microscopy (before, 1 week, and 5-7 weeks after initiation of therapy) indicated that a transient increase in VLDL size occurred in response to cholestyramine. The results are consistent with a stimulatory effect of bile acid sequestrants on VLDL triglyceride production and indicate that, in most subjects, a compensatory increase in VLDL triglyceride removal occurs.     

血脂对骨关节炎影响研究进展

骨关节炎(osteoarthritis,OA),—种常见的肌肉骨骼性疾病,是造成老年人下肢残疾的重要原因,也是造成社会经济负担最大的疾病之一,其病理表现为滑膜炎、软骨损伤、骨赘形成以及软骨下骨的重塑,常可累及手、髓、膝等多个关节。全世界大约有25%的人患OA,我国以膝骨关节炎(knee osteoarthritis,KOA)最常见⑴。OA最常发生于中老年女性,其发病原因迄今为止尚不明了,因此,当前临床中仍缺乏有效的治疗办法。     

他汀类药物抵抗及其分子机制研究进展

血脂异常是心血管病的主要危险因素,尤其是低密度脂蛋白胆固醇(LDLC)升高显著增加动脉粥样硬化性心血管疾病(ASCVD)发病率。他汀类药物已被证实可以有效降低血清LDLC,进而减少ASCVD发生风险。但是在他汀类药物的临床应用过程中,越来越多的研究显示他汀类药物存在耐药性,即药物抵抗。研究表明,他汀类药物抵抗主要受药物在体内的吸收、转运、代谢以及药物作用本身的影响。深入研究他汀类药物抵抗可为进一步揭示他汀类药物作用机制提供理论依据,并有望为研发新的降脂药物提供靶点。     

Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations.

Elevated plasma insulin and triglyceride (TG) and decreased high-density-lipoprotein (HDL)-cholesterol concentrations have been shown to be risk factors for coronary heart disease (CHD). It has been suggested that these metabolic abnormalities are all secondary to resistance to insulin-stimulated glucose uptake. To examine this in more detail, we divided 18 non-diabetic, moderately overweight, sedentary men aged 25-50 years into three groups on the basis of their steady-state plasma glucose levels (SSPG): a low group, (n = 7; SSPG less than 8.3 mmol l-1), a middle group, (n = 6; SSPG 8.3-11.1 mmol l-1), and a high group (n = 5; SSPG greater than 11.1 mmol l-1). The high group had significantly higher fasting (P less than 0.05) and post-oral glucose challenge (P less than 0.01) insulin concentrations, higher fasting TG (P less than 0.05) and lower fasting HDL-cholesterol (P less than 0.05) concentrations than the other two groups. However, there were no statistically significant differences between the groups with regard to body mass index, waist-to-hip ratio or physical endurance capacity as determined by maximal oxygen consumption during a treadmill test. The data suggest that insulin resistance has an effect on the modulation of plasma insulin, TG and HDL-cholesterol concentrations, independent of generalized, abdominal or physical endurance capacity.     

甘油三酯/高密度脂蛋白胆固醇比值与缺血性脑卒中患者颈动脉斑块不稳定性的相关性

目的探讨缺血性脑卒中(IS)患者甘油三酯/高密度脂蛋白胆固醇比值(TG/HDLC)与颈动脉斑块不稳定性的相关性。方法回顾性纳入2019年1月—2020年1月期间在保定市第一中心医院神经内科就诊的急性IS患者594例。所有研究对象均行超声检查了解颈动脉斑块情况,并依据超声结果将研究对象分为无斑块组(105例)、稳定性斑块组(63例)、不稳定性斑块组(426例)。全自动生化分析仪检测常规生物化学指标及各血脂指标,比较各组的危险因素、生物化学指标及血脂的差异。采用多变量Logistic回归分析评估颈动脉斑块不稳定性的影响因素,并计算优势比(OR)及95%可信区间(95%CI)。采用受试者工作特征(ROC)曲线分析TG/HDLC对颈动脉斑块不稳定性的预测价值。结果594例IS患者中,无颈动脉狭窄105例,有颈动脉狭窄489例,其中轻度狭窄439例,中度狭窄20例,重度狭窄30例。不稳定性斑块组的男性、体质指数(BMI)、吸烟史、饮酒史、血红蛋白、TG/HDLC高于稳定性斑块组,年龄、HDLC低于稳定性斑块组(P<0.05)。多变量Logistic回归分析显示,TG/HDLC是颈动脉斑块不稳定性的独立危险因素(OR 1.618,95%CI 1.027~2.551,P=0.038)。ROC曲线分析显示,TG/HDLC预测颈动脉斑块不稳定性的曲线下面积为0.619(95%CI 0.542~0.696),最佳截断值为1.60,灵敏度为35.4%,特异度为84.1%。结论TG/HDLC是IS患者颈动脉斑块不稳定性的独立危险因素,对颈动脉不稳定性斑块有一定预测价值。