Leyva F, Godsland I F, Ghatei M, Proudler A J, Aldis S, Walton C, Bloom S, Stevenson J C
Wynn Department of Metabolic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK.
Arterioscler Thromb Vasc Biol. 1998 Jun;18(6):928-33. doi: 10.1161/01.atv.18.6.928.
In humans, production of the adipocyte-derived peptide leptin has been linked to adiposity, insulin, and insulin sensitivity. We therefore considered that alterations in plasma leptin concentrations could constitute an additional component of a metabolic syndrome of cardiovascular risk. To explore this hypothesis, we employed factor analysis, a multivariate statistical technique that allows reduction of large numbers of highly intercorrelated variables to composite, biologically meaningful factors. Seventy-four men [age, 48.4+/-1.3 years (mean+/-SEM); body mass index (BMI), 25.6+/-0.3 kg/m2] who were free of coronary heart disease and diabetes underwent anthropometric measurements (subscapular-to-triceps [S:T] and subscapular-to-biceps [S:B] skinfold thickness ratios, measurement of fasting plasma leptin, and an intravenous glucose tolerance test (IVGTT) for assessment of insulin sensitivity. Plasma leptin concentrations were correlated with BMI (r=0.57, P<0.001), S:T (r=0.34, P=0.003), S:B (r=0.37, P<0.001), systolic and diastolic blood pressures (both r=0.24, P=0.044), fasting triglycerides (r=0.31, P=0.007), serum uric acid (r=0.35, P=0.003), fasting glucose (r=0.32, P=0.003) and insulin (r=0.33, P=0.004), and IVGTT insulin (r=0.63, P<0.001). A negative correlation was observed between leptin and insulin sensitivity (r=-0.32, P=0.006). No significant correlations emerged between plasma leptin concentrations and age, high density lipoprotein cholesterol, or IVGTT glucose. In multivariate regression analyses, BMI (standardized coefficient [SC]=0.40, P=0.001), fasting insulin (SC=0.23, P=0.036), and IVGTT insulin (SC=0.51, P<0.001) emerged as independent predictors of plasma leptin concentrations (R2=0.56, P<0.001). After adjustment for BMI, only IVGTT insulin emerged as a significant predictor of plasma leptin concentrations (SC=0.56, P<0.001, R2=0.45, P<0.001). Factor analysis of plasma leptin concentrations and the variables that are considered relevant to the insulin resistance syndrome revealed a clustering of plasma leptin concentrations with a factor dominated by insulin resistance and high IVGTT insulin, separate from a high IVGTT glucose/central obesity factor and a high triglyceride/low high density lipoprotein cholesterol factor. Together, these factors accounted for 55.9% of the total variance in the dataset. In conclusion, interindividual variations in plasma leptin concentrations are strongly related to the principal components of the insulin resistance syndrome. Further studies are needed to determine whether the insulin-leptin axis plays a coordinating role in this syndrome and whether plasma leptin concentrations could provide an additional measure of cardiovascular risk.
在人类中，脂肪细胞衍生肽瘦素的产生与肥胖、胰岛素及胰岛素敏感性相关。因此，我们认为血浆瘦素浓度的改变可能构成心血管风险代谢综合征的一个额外组成部分。为探究这一假说，我们采用了因子分析，这是一种多变量统计技术，可将大量高度相关的变量简化为综合的、具有生物学意义的因子。74名无冠心病和糖尿病的男性[年龄，48.4±1.3岁（均值±标准误）；体重指数（BMI），25.6±0.3kg/m²]接受了人体测量（肩胛下至肱三头肌[S:T]及肩胛下至肱二头肌[S:B]皮褶厚度比值）、空腹血浆瘦素测量以及用于评估胰岛素敏感性的静脉葡萄糖耐量试验（IVGTT）。血浆瘦素浓度与BMI（r = 0.57，P < 0.001）、S:T（r = 0.34，P = 0.003）、S:B（r = 0.37，P < 0.001）、收缩压和舒张压（两者r = 0.24，P = 0.044）、空腹甘油三酯（r = 0.31，P = 0.007）、血清尿酸（r = 0.35，P = 0.003）、空腹血糖（r = 0.32，P = 0.003）及胰岛素（r = 0.33，P = 0.004）以及IVGTT胰岛素（r = 0.63，P < 0.001）相关。瘦素与胰岛素敏感性之间存在负相关（r = -0.32，P = 0.006）。血浆瘦素浓度与年龄、高密度脂蛋白胆固醇或IVGTT血糖之间未出现显著相关性。在多变量回归分析中，BMI（标准化系数[SC] = 0.40，P = 0.001）、空腹胰岛素（SC = 0.23，P = 0.036）及IVGTT胰岛素（SC = 0.51，P < 0.001）成为血浆瘦素浓度的独立预测因子（R² = 0.56，P < 0.001）。在对BMI进行校正后，仅IVGTT胰岛素成为血浆瘦素浓度的显著预测因子（SC = 0.56，P < 0.001，R² = 0.45，P < 0.001）。对血浆瘦素浓度及与胰岛素抵抗综合征相关的变量进行因子分析发现，血浆瘦素浓度聚集在一个以胰岛素抵抗和高IVGTT胰岛素为主导的因子中，与高IVGTT血糖/中心性肥胖因子及高甘油三酯/低高密度脂蛋白胆固醇因子分开。这些因子共同解释了数据集中总方差的55.9%。总之，血浆瘦素浓度的个体间差异与胰岛素抵抗综合征的主要成分密切相关。需要进一步研究以确定胰岛素 - 瘦素轴在该综合征中是否起协调作用以及血浆瘦素浓度是否可为心血管风险提供额外的衡量指标。
