Carbohydrate & Lipid Metabolism Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Metab Syndr Relat Disord. 2012 Oct;10(5):351-7. doi: 10.1089/met.2012.0063. Epub 2012 Jul 20.
Insulin resistance is thought to play a pathophysiological role in the development of atherosclerosis. Decreased adiponectin levels are associated with hyperinsulinemia, insulin resistance, and coronary artery disease. Patients with familial hypercholesterolemia (FH) develop premature atherosclerosis and should be insulin resistant and have low adiponectin levels.
A total of 51 homozygous FH (HoFH) and 20 heterozygous FH (HeFH) patients were studied before and after statin therapy. Twenty normocholesterolemic subjects were controls. Fasting lipograms, glucose, insulin, proinsulin, adiponectin, and high-sensitivity C-reactive protein (hsCRP) were measured. Insulin resistance was calculated with the homeostasis model assessment (HOMA-IR) formula. Carotid intima media thickness (CIMT) was measured as a subclinical marker of atherosclerosis.
On multiple regression analysis, the major determinant of insulin resistance measured by HOMA-IR was body mass index (BMI) (r=0.54; P=0.004). On simple linear regression, the highest correlation was with BMI (r=0.39; P=0.0002). Log hsCRP correlated with BMI (r=0.35; P<0.002) and insulin resistance (r=0.22; P=0.05). Low-density lipoprotein cholesterol (LDL-C) and CIMT did not correlate with insulin resistance. Unexpectedly, adiponectin levels were highest in HoFH patients and correlated with LDL-C (r=0.34; P=0.001). No change in the degree of IR was observed with statin therapy.
FH patients are not insulin resistant and do not have low adiponectin levels. There was no significant change in insulin resistance with high-dose statin therapy.
胰岛素抵抗被认为在动脉粥样硬化的发展中起病理生理作用。脂联素水平降低与高胰岛素血症、胰岛素抵抗和冠心病有关。家族性高胆固醇血症（FH）患者会过早发生动脉粥样硬化，并且应该存在胰岛素抵抗和低脂联素水平。
本研究共纳入了 51 名纯合子 FH（HoFH）和 20 名杂合子 FH（HeFH）患者，在他汀类药物治疗前后进行了研究。20 名血脂正常的受试者作为对照组。检测了空腹血脂谱、血糖、胰岛素、胰岛素原、脂联素和高敏 C 反应蛋白（hsCRP）。采用稳态模型评估（HOMA-IR）公式计算胰岛素抵抗。颈动脉内膜中层厚度（CIMT）作为动脉粥样硬化的亚临床标志物进行了测量。
在多元回归分析中，HOMA-IR 测量的胰岛素抵抗的主要决定因素是体重指数（BMI）（r=0.54；P=0.004）。简单线性回归显示，与 BMI 的相关性最高（r=0.39；P=0.0002）。hsCRP 与 BMI（r=0.35；P<0.002）和胰岛素抵抗（r=0.22；P=0.05）呈正相关。低密度脂蛋白胆固醇（LDL-C）和 CIMT 与胰岛素抵抗无关。出乎意料的是，HoFH 患者的脂联素水平最高，且与 LDL-C 呈正相关（r=0.34；P=0.001）。他汀类药物治疗并未观察到胰岛素抵抗程度的显著变化。
FH 患者无胰岛素抵抗，且脂联素水平不低。高剂量他汀类药物治疗并未显著改变胰岛素抵抗程度。
