Beyond fasting plasma glucose: The association between coronary heart disease risk and postprandial glucose,postprandial insulin and insulin resistance in healthy,nondiabetic adults

Objective

Prediabetes is defined by elevations of plasma glucose concentration, and is aimed at identifying individuals at increased risk of type 2 diabetes and coronary heart disease (CHD). However, since these individuals are also insulin resistant and hyperinsulinemic, we evaluated the association between several facets of carbohydrate metabolism and CHD risk profile in apparently healthy, nondiabetic individuals.

Methods

Plasma glucose and insulin concentrations were measured before and at hourly intervals for eight hours after two test meals in 281 nondiabetic individuals. Insulin action was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. CHD risk was assessed by measurements of blood pressure and fasting lipoprotein profile.

Results

For purposes of analysis, the population was divided into tertiles, and the results demonstrated that the greater the 1) fasting plasma glucose (FPG) concentration, 2) incremental plasma insulin response to meals, and 3) SSPG concentration, the more adverse the CHD risk profile (p < 0.05). In contrast, the CHD risk profile did not significantly worsen with increases in the incremental plasma glucose response to meals.

Conclusions

In nondiabetic individuals, higher FPG concentrations, accentuated daylong incremental insulin responses to meals, and greater degrees of insulin resistance are each associated with worse CHD risk profile (higher blood pressures, higher triglycerides, and lower high density lipoprotein cholesterol concentrations). Interventional efforts aimed at decreasing CHD in such individuals should take these abnormalities into consideration.     

Elevated plasma fractalkine levels are associated with higher levels of IL-6, Apo-B,LDL-C and insulin,but not with body composition in a large female twin sample

Objective

Plasma fractalkine (FRACT) is involved in the development of numerous inflammatory conditions including atherosclerosis. It is associated with type 2 diabetes mellitus and adipose inflammation. However, whether FRACT is associated with major risk factors for cardiovascular disease, in particular obesity, metabolic syndrome and blood lipids, is virtually unknown.

Methods

The study included a large community-based sample of 3306 middle-aged women drawn from the general UK population. Blood samples were analyzed for circulating levels of FRACT, leptin, insulin, glucose, LDL-C, HDL-C, Apo-A, ApoB and IL-6. Obesity was assessed by fat body mass (FBM) using dual-energy x-ray absorptiometry and by body mass index (BMI).

Results

We found no association between FRACT and body composition, in particular adiposity. Obese and non obese subjects with metabolic syndrome tended to have higher levels of FRACT compared with non-obese subjects without metabolic syndrome but this did not reach statistical significance. Most importantly we report significant correlations between FRACT and circulating IL-6, Apo-B, LDL-C and insulin. The associations with IL-6 and Apo-B were particularly significant (P-value < 0.001), and survived correction for multiple testing and adjustment for age and other covariates.

Conclusion

Higher FRACT levels correlated with elevated levels of IL-6, Apo-B, LDL-C and insulin, all known risk factors for several clinical related diseases suggesting a potential role of FRACT in inflammation and tissue injury. Variations of FRACT levels are not influenced by body composition and are not correlated with leptin indicating that fat mass alone is not responsible for elevation of FRACT seen in obese individuals.     

中国西北地区汉族人群三磷酸腺苷结合盒转运体A1-V771M与血浆高密度脂蛋白胆固醇水平及冠心病的相关性

目的:探讨中国西北地区汉族人群三磷酸腺苷结合盒转运体A1(ABCA1)的V771 M单核苷酸多态性(SNPs)与血浆HDL水平和冠心病(CHD)的关系。方法:采用病例对照研究,选择经选择性冠状动脉造影(CAG)的中国西北地区汉族人群292例,其中CHD患者176例,正常对照组111例,被剔除5例,聚合酶链反应-限制性片段长度多态性法检测ABCA1-V771 M多态性的基因型,计算V771 M各基因型及等位基因频率分布,分别比较V771 M不同基因型组间临床及血脂生化等指标,分析V771 M多态性对HDL-C水平和CHD的影响。结果:中国西北地区汉族人群的ABCA1-V771 M多态性分布符合Hardy-Weinberg平衡规律,V、M等位基因频率分别为33.91%和66.09%。MM型的HDL-C水平明显低于VV加VM型(P<0.01),但其余血脂成分水平与V771 M各基因型均无相关性(P>0.05)。M等位基因在CHD组的分布频率明显高于V等位基因(P<0.05),M等位基因相关的冠状动脉病变程度显著高于V等位基因(P<0.05),ABCA1-V771 M3种基因型的急性心肌梗死发生率差异无统计学意义(P>0.05)。结论:在中国西北地区汉族人群中,ABCA1-V771 M多态性不仅与血浆HDL-C水平明显相关,而且与CHD易感性及冠状动脉病变严重程度明显相关,V771 M的M等位基因具有致冠状动脉粥样硬化和CHD的遗传学功能。     

鹿茸提取物复方对骨质疏松症调节作用

目的 探讨鹿茸提取物复方对糖皮质激素性骨质疏松症(GIO)大鼠脂类代谢指标影响及机制。方法将79只Wistar大鼠随机分为对照组、模型组、鹿茸组及骨疏康组,采用后肢肌注地塞米松(2.5 mg/kg,每周2次)造模,造模同时,鹿茸组(0.439 g/kg)及骨疏康组(2.1 g/kg)灌胃处理,连续9周,采用骨密度仪测定大鼠股骨骨密度、自动生化分析仪测定血清高密度脂蛋白胆固醇(HDL-C)含量、实时定量PCR法及Western blot法测定骨组织脂肪细胞型脂肪酸结合蛋白(A-FABP) mRNA和蛋白表达。结果 对照组、模型组、鹿茸组及骨疏康组大鼠股骨骨密度分别为(0.116±0.009)、(0.108±0.006)、(0.115±0.009)、(0.111±0.006) g/cm²,血清HDL-C含量分别为(0.503±0.013)、(0.352±0.017)、(0.496±0.023)、(0.383±0.015) mmol/L;与对照组比较,模型组大鼠股骨骨密度、血清HDL-C含量明显降低(P<0.01),股骨A-FABP mRNA和蛋白表达明显增强(P<0.01);与模型组比较,鹿茸组大鼠股骨骨密度、血清HDL-C含量明显升高(P<0.01),股骨A-FABP mRNA及蛋白表达明显降低(P<0.01)。结论 鹿茸提取物复方对大鼠GIO具有一定干预作用,其机制可能与降低大鼠血清中HDL-C含量、升高骨组织A-FABP表达有关。     

胆固醇/高密度脂蛋白-胆固醇比值在脑梗死中的价值研究

目的:探讨胆固醇/高密度脂蛋白-胆固醇比值(TC/HDL-C比值)与脑梗死发病危险性的关系以及这一比值在脑梗死患者合并高血压或糖尿病时的变化。方法:选择197例脑梗死患者分为三组:单纯脑梗死组、合并高血压组、合并糖尿病组。58例健康者作为正常对照组,探讨这一比值的变化。结果:胆固醇(TC)水平及TC/HDL-C比值在脑梗死患者与正常对照组间有显著性差异(P<0.05);脑梗死患者的HDL-C水平较正常对照组降低,但两者差异无显著性(P>0.05);不同病例组间TC、HDL-C水平及TC/HDL-C比值无显著性差异(P>0.05)。结论:TC/HDL-C比值是脑梗死的危险因素,与高血压、糖尿病无关。     

Serum levels of polyunsaturated fatty acids are low in Chinese men with metabolic syndrome,whereas serum levels of saturated fatty acids,zinc, and magnesium are high

The purpose of this study was to examine the hypothesis that serum levels of phospholipid (PL) fatty acids (FA) and minerals are associated with the components of metabolic syndrome (MetS) in the Chinese population and the profiles of changes may differ from patients with MetS from Western countries. The levels of serum PL, FA, and minerals were examined in 201 subjects (52 with MetS and 149 healthy controls without any MetS components) in China. The saturated FA proportion in serum was significantly higher, whereas the proportion of total polyunsaturated FA (PUFA), n-3 and n-6 PUFA (22:6n-3: −16%, P = .006; 20:4n-6: −36%, P < .001), and estimated δ-5 desaturase were significantly lower in the MetS group compared with those that are not MetS. Subjects with MetS had higher levels of serum Zn (P = .037) and Mg (P < .001) than subjects without MetS. The proportion of n-3 PUFA was significantly negatively correlated with body mass index and waist circumference. In conclusion, serum PL FA composition and serum minerals in Chinese men with MetS differed significantly from that of healthy individuals, reflecting a decrease in n-3 and n-6 PUFA, especially 22:6n-3 and 20:4n-6, and an increase in saturated FA, magnesium, and zinc. These changes may reflect improper dietary intake in subjects with MetS, and dietary modification could be useful to prevent MetS and as an adjunctive therapy.     

Stereology of the myocardium and blood biochemistry in aged rats fed with a cholesterol-rich and canola oil diet (n-3 fatty acid rich)

The myocardial changes brought about by canola oil (n-3 fatty acid rich) and hyperlipidic diets were studied in 45 rats. Three groups each consisting of 15 animals was separated into (A) which receiving a normal balanced diet; and in groups (CHO) and (O) the animals receiving hyperlipidic and canola oil diet, respectively. These diets were fed to the animals from 21 days until 15 months old, then a blood analysis was performed, after which they were sacrificed and the hearts taken for light microscopic studies. The total lipids serum was extracted and the low density lipoproteins (LDL-C and VLDL-C) and chylomicron fractions were determined as well as the cholesterol concentration in the high density lipoprotein fraction (HDL-C). The myocardium was composed of myocytes and cardiac interstitium, which is made up of connective tissue and blood vessels. The following stereological parameters were determined: a) from myocyte: volume density of myocyte, total volume of myocytes surface density of myocyte, total surface of myocyte and cross sectional area of myocyte; b) from blood vessels: volume density of blood vessels, total volume of blood vessels, length density of blood vessels, surface density of blood vessels, total surface of blood vessels and cross sectional area of vessels; c) from connective tissue: volume density of connective tissue and total volume of connective tissue. The differences were tested by the analysis of variance and Tukey test. The Mantel-Haenezel test analyzed the survival curve test comparing the different groups. Many stereological parameters had significant differences: cardiac weight, thickness of the right and left ventricular wall, aorta and pulmonary artery inner diameters, HDL-C, LDL-C, volume density of myocyte, total surface of myocyte, surface density of myocyte, total surface of myocyte, total volume of blood vessel, length density of blood vessels, surface density of blood vessels, total surface of blood vessels, volume density of connective tissue, total volume of connective tissue. Differences in survival curves were significant between groups CHO×A and CHO×O (p<0.05) but not between groups A×O (p=0.48). For the cardiac weight, the smallest values were found in group O. The aorta and artery pulmonary internal diameters were smaller in group CHO. The HDL-C serum was about 40% greater in group O. The LDL-C serum was more than 80% less in the same group. The average of volume density of myocyte was less in group CHO, while the average of volume density of connective tissue was greater in group CHO in comparison to groups A and O. The length density of blood vessels was greater in group O than in groups A and CHO. The surface density of myocyte and surface density of blood vessels were smaller in group CHO and greater in group A. The total surface of myocyte and total surface of blood vessels were greater in group CHO and smaller in group O. Differences were significant between groups A×CHO. The total volume of myocytes was greater in group A, while the total volume of connective tissue was greater in group CHO. The cross sectional area of myocyte and cross sectional area of vessels were greater in group CHO and smaller in group O suggesting that the canola oil diet (n-3 fatty acid rich) preserves the myocardium more than the standard and cholesterol-rich diets. Received: 7 April 1997, Returned for 1. Revision: 6 May 1997, 1. Revision received: 15 July 1997, Returned for 2. Revision: 29 August 1997, 2. Revision received: 15 October 1997, Accepted: 28 October 1997     

高密度脂蛋白胆固醇直接测定方法学评价

作者通过一系列实验,从稳定性、特异性、线性和回归分析,干扰物分析及方法学比较等方面对高密度脂蛋白胆固醇的无标本预处理的直接测定法进行了讨论。HDL—C重复测定的最大CV为5.7％,直接法与磷酸钨镁沉淀法有很好的相关性,Y=0.00256±XO.045mmol/1,r=0.970。当TG=2.2时,HDL—C的浓度仅增加2％,Hb对结果有明显的正干扰作用,而胆红素却使HDL—C的结果偏低。实验表明,HDL—C的直接测定法具有操作简单,一定条件下结果稳定,准确,能够应用于全自动分析的特点,该方法对于人群血脂代谢的筛查工作,及时发现和预防心血管疾患的危险致病因素提供了相当便利的条件。     

Modulation of HDL metabolism by the niacin receptor GPR109A in mouse hepatocytes

The niacin receptor GPR109A is a G_i-protein-coupled receptor which mediates the effects of niacin on inhibiting intracellular triglyceride lipolysis in adipocytes. However, the role of GPR109A in mediating the effects of niacin on high density lipoprotein (HDL) metabolism is unclear. We found niacin has no effect on HDL-C in GPR109A knockout mice. Furthermore, niacin lowered intracellular cAMP in primary hepatocytes mediated by GPR109A. We used an adeno-associated viral (AAV) serotype 8 vector encoding GPR109A under the control of the hepatic-specific thyroxine-binding globulin promoter to specifically overexpress GPR109A in mouse liver. Plasma HDL-C, hepatic ABCA1 and the HDL cholesterol production rate were significantly reduced in mice overexpressing GPR109A. Overexpression of GPR109A reduced primary hepatocyte free cholesterol efflux to apoA-I; conversely, GPR109A deficient hepatocytes had increased ABCA1-mediated cholesterol efflux. These data support the concept that the HDL-C lowering effect of niacin in wild-type mice is mediated through stimulation of GPR109A in hepatocytes; such an effect then leads to reduced hepatocyte ABCA1 expression and activity, decreased cholesterol efflux to nascent apoA-I, and reduced HDL-C levels. These results indicate that niacin-mediated activation of GP109A in liver lowers ABCA1 expression leading to reduced hepatic cholesterol efflux to HDL.     

Association between apolipoprotein E polymorphism and serum lipid and apolipoprotein levels with Alzheimer's disease

We have recently demonstrated that apolipoprotein E (APOE)-varepsilon4 allele is a risk factor for Alzheimer disease (AD) in Tehran, Iran. The current study specifically aimed to examine whether APOE polymorphism in association with serum lipids-apolipoprotein level is a risk factor for AD in a population from Tehran, Iran. APOE polymorphism and plasma lipids, apoA1, apoB and lipoprotein (a) (Lp(a)) levels were determined in 94 AD patients and 111matched controls. Our study demonstrated a significant association between APOE polymorphism and the level of plasma lipids and apolipoprotein with AD in this population. The AD subjects had significantly lower apoA1 (p<0.001) and HDL-C (p<0.01) and higher apoB (p=0.01) and LDL-C (p=0.02) levels than that of the control group. The AD subjects carrying APOE-varepsilon4 allele had lower plasma apoA1 (t=5.2, p<0.002) and HDL-C level (t=2.7, p=0.01) but had higher plasma apoB (t=-5.4, p<0.002), LDL-C (t=-4.6, p=0.005) and total cholesterol (TC) (t=-2.7, p=0.01) than that of the non APOE-varepsilon4 carriers. These results indicated that AD patients with APOE-varepsilon4 allele has a distinct plasma lipid profile and carrier of this allele with low levels of apoA1 and HDL-C may be more susceptible to AD.