Pihlajamäki Jussi, Gylling Helena, Miettinen Tatu A, Laakso Markku
Department of Medicine, University of Kuopio, Kuopio, Finland.
J Lipid Res. 2004 Mar;45(3):507-12. doi: 10.1194/jlr.M300368-JLR200. Epub 2003 Dec 1.
Type 2 diabetes has been associated with high synthesis and low absorption of cholesterol independent of weight, indicating that insulin resistance may be a link between glucose and cholesterol metabolism. Therefore, we investigated the relationship of serum cholesterol precursors, reflecting cholesterol synthesis, and serum plant sterols and cholestanol, reflecting cholesterol absorption efficiency, with insulin sensitivity measured with the hyperinsulinemic euglycemic clamp in 72 healthy normoglycemic men. Men in the most insulin-resistant tertile had higher serum cholesterol precursor ratios (P < 0.05), whereas no significant differences in serum absorption sterols were observed. In bivariate analysis, cholesterol synthesis markers correlated with fasting insulin (r = 0.36-0.46, P < 0.01) and the rates of insulin-stimulated whole-body glucose uptake (WBGU; r = -0.37-0.40, P < 0.01). Also, cholesterol absorption markers correlated with fasting insulin and WBGU (P < 0.05). Fasting insulin correlated with desmosterol (r = 0.286, P = 0.015) and lathosterol (r = 0.248, P = 0.037) even when the rates of WBGU and body mass index (BMI) were controlled for. We conclude that insulin resistance is linked to high cholesterol synthesis and decreased cholesterol absorption. Because fasting insulin correlated with cholesterol synthesis independent of the rates of BMI and WBGU, it is possible that regulation of cholesterol synthesis by hyperinsulinemia may be a link between insulin resistance and cholesterol metabolism.
2型糖尿病与胆固醇的高合成及低吸收有关，且与体重无关，这表明胰岛素抵抗可能是葡萄糖和胆固醇代谢之间的一个联系。因此，我们在72名健康的血糖正常男性中，通过高胰岛素正常血糖钳夹技术测量胰岛素敏感性，研究了反映胆固醇合成的血清胆固醇前体以及反映胆固醇吸收效率的血清植物甾醇和胆甾烷醇之间的关系。胰岛素抵抗最严重的三分位数组男性的血清胆固醇前体比率更高（P < 0.05），而血清吸收甾醇未观察到显著差异。在双变量分析中，胆固醇合成标志物与空腹胰岛素（r = 0.36 - 0.46，P < 0.01）以及胰岛素刺激的全身葡萄糖摄取率（WBGU；r = -0.37 - 0.40，P < 0.01）相关。此外，胆固醇吸收标志物与空腹胰岛素和WBGU相关（P < 0.05）。即使控制了WBGU率和体重指数（BMI），空腹胰岛素仍与羊毛甾醇（r = 0.286，P = 0.015）和7-脱氢胆固醇（r = 0.248，P = 0.037）相关。我们得出结论，胰岛素抵抗与高胆固醇合成及胆固醇吸收降低有关。由于空腹胰岛素与胆固醇合成相关，且独立于BMI和WBGU率，高胰岛素血症对胆固醇合成的调节可能是胰岛素抵抗和胆固醇代谢之间的一个联系。
