Stranberg T E, Salomaa V, Vanhanen H, Miettinen T A
Department of Medicine, University of Helsinki, Finland.
Diabetes. 1996 Jun;45(6):755-61. doi: 10.2337/diab.45.6.755.
NIDDM and the metabolic syndrome are characterized by a low serum, HDL cholesterol content and a high triglyceride level, whereas total and LDL cholesterol concentrations are not necessarily elevated. Variable results have been reported on cholesterol absorption, elimination, and synthesis in NIDDM, but no studies are available on subjects within the normal range of blood glucose. From serum samples collected in 1985 from 203 nondiabetic men aged 51-66 years, we examined lipids, cholesterol precursors (reflecting cholesterol synthesis), and plant sterols and cholestanol (reflecting cholesterol absorption) in relation to fasting blood glucose. The findings prompted us (in 1993) to further examine 11 men from the highest and lowest glucose thirds of 203 nondiabetic men by additional dietary, serum, and fecal analyses for absorption, elimination, and synthesis of cholesterol and insulin sensitivity. In 1985, blood glucose was significantly related to LDL apolipoprotein B (P = 0.05) but not to LDL cholesterol (P = 0.19). Significantly higher serum lathosterol and desmosterol-to-cholesterol proportions and lower plant sterol and cholestanol proportions in the highest rather than the lowest glucose thirds suggested that the subjects with high normal blood glucose had decreased absorption and enhanced synthesis of cholesterol. In 1993, men with the lowest glucose versus those with the highest glucose had a lower waist-to-hip ratio, plasma HbA1c, fasting and postload insulin and glucose values, and a higher insulin sensitivity index. In agreement with the 1985 non-cholesterol sterol data, direct analyses of cholesterol metabolism showed further higher cholesterol absorption efficiency (P = 0.03) and serum plant sterol and cholestanol proportions (P < 0.001). Despite a slightly lower dietary cholesterol intake, cholesterol synthesis (P = 0.02) and serum lathosterol (P < 0.01) and desmosterol (P < 0.01) proportions were lowest in men with the lowest glucose third. We conclude that noncholesterol sterols in serum exhibits a long-lasting correlation with blood glucose level in a nondiabetic male population. Low intestinal absorption and high synthesis of cholesterol characterize men with high normal blood glucose. Differences in cholesterol metabolism could be due to underlying insulin effects associated with obesity-like fat distribution and may thus imply novel aspects in the metabolic interrelation between insulin and cholesterol in humans.
非胰岛素依赖型糖尿病（NIDDM）和代谢综合征的特征是血清高密度脂蛋白胆固醇含量低、甘油三酯水平高，而总胆固醇和低密度脂蛋白胆固醇浓度不一定升高。关于NIDDM患者胆固醇吸收、清除和合成的研究结果不一，但尚无针对血糖在正常范围内的受试者的研究。我们从1985年收集的203名年龄在51 - 66岁的非糖尿病男性的血清样本中，检测了血脂、胆固醇前体（反映胆固醇合成）以及植物甾醇和胆甾烷醇（反映胆固醇吸收）与空腹血糖的关系。这些发现促使我们（在1993年）通过额外的饮食、血清和粪便分析，对203名非糖尿病男性中血糖最高和最低的三分之一人群中的11名男性进行进一步研究，以分析胆固醇的吸收、清除和合成以及胰岛素敏感性。1985年，血糖与低密度脂蛋白载脂蛋白B显著相关（P = 0.05），但与低密度脂蛋白胆固醇无关（P = 0.19）。血糖最高的三分之一人群中，血清羊毛甾醇和链甾醇与胆固醇的比例显著高于最低的三分之一人群，而植物甾醇和胆甾烷醇的比例则较低，这表明血糖处于正常高值的受试者胆固醇吸收减少、合成增加。1993年，血糖最低的男性与血糖最高的男性相比，腰臀比、血浆糖化血红蛋白A1c、空腹和负荷后胰岛素及血糖值较低，胰岛素敏感性指数较高。与1985年非胆固醇甾醇数据一致，对胆固醇代谢的直接分析显示，胆固醇吸收效率更高（P = 0.03），血清植物甾醇和胆甾烷醇比例更高（P < 0.001）。尽管饮食中胆固醇摄入量略低，但血糖最低的三分之一人群中胆固醇合成（P = 0.02）以及血清羊毛甾醇（P < 0.01）和链甾醇（P < 0.01）比例最低。我们得出结论，在非糖尿病男性人群中，血清中的非胆固醇甾醇与血糖水平存在长期相关性。血糖处于正常高值的男性其胆固醇的肠道吸收低、合成高。胆固醇代谢的差异可能归因于与肥胖样脂肪分布相关的潜在胰岛素效应，因此可能暗示了人类胰岛素与胆固醇代谢相互关系中的新方面。
