Fasting plasma homocysteine levels in the insulin resistance syndrome - The Framingham Offspring Study
Fasting plasma homocysteine levels in the insulin resistance syndrome - The Framingham Offspring Study
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DOI：
10.2337/diacare.24.8.1403
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发表时间：
2001-08-01
期刊：
影响因子：
16.2
通讯作者：
Wilson, PWF
中科院分区：
文献类型：
--
作者：
Meigs, JB;Jacques, PF;Wilson, PWF
胰岛素抵抗、相关的代谢异常和高同型半胱氨酸水平是心血管疾病的危险因素.研究设计和方法-我们测量了2名受试者的空腹同型半胱氨酸、叶酸、B族维生素、肌酐的临床特征血浆水平，以及在75克口服葡萄糖耐量试验后空腹和2小时胰岛素和葡萄糖水平，214例受试者在第五次检查（1991-1995年）的Frachial Offspring研究中没有CVD。在排除203名糖尿病患者后，剩下的2,011名患者被分为没有、有一种、两种或所有三种IRS表型：糖耐量受损、高血压和/或中枢代谢综合征（两个或多个特征：肥胖、血脂异常或高胰岛素血症），此外，在参加第六次检查的1，592名受试者中，（1995-1998）测定尿白蛋白/肌酐比值（UACR）。年龄、性别、肌酐、维生素和UACR校正平均值。结果-受试者的平均年龄为54岁（范围28-82），55%为女性，12.3%有高胰岛素血症，15.9%有两种或多种IRS表型。校正后的平均同型半胱氨酸水平高于有高胰岛素血症的受试者（9.8 μ mol/l）和无高胰岛素血症的受试者（9.4 μ mol/l，P = 0.04），具有两种或两种以上IRS表型的受试者（9.9 μ mol/l）高于I型或无表型的受试者（9.3 μ mol/l，P = 0.003）。平均UACR水平也较高的两个或两个以上的IRS表型（7.2毫克/克）与I或无表型（5.5毫克/克，P = 0.007）相比，高同型半胱氨酸血症和异常尿白蛋白排泄都与高胰岛素血症，并可能部分帐户与胰岛素抵抗相关的心血管疾病的风险增加。由于高同型半胱氨酸血症和微量白蛋白尿也反映了内皮损伤，这些观察结果也支持内皮功能障碍与IRS表达相关的假设。
OBJECTIVE - insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS).RESEARCH DESIGN AND METHODS - We measured clinical characteristics plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the Fifth examination (1991-1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia), In addition, in 1,592 subjects attending the sixth examination (1995-1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean. homocysteine levels or proportions with homocysteine > 14 mu mol/l in each phenotypic category and differences between categories were assessed with regression models.RESULTS - The mean age of the Subjects was 54 years (range 28-82) 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 mu mol/l) and those without (9.4 mu mol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 mu mol/l) compared with those with I or no phenotype (9.3 mu mol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with I or no phenotype (5.5 mg/g, P = 0.007).CONCLUSIONS - Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocystememia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.