Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
PLoS One. 2013 Jun 28;8(6):e67406. doi: 10.1371/journal.pone.0067406. Print 2013.
We investigated the levels of non-cholesterol sterols as predictors for the development of hyperglycemia (an increase in the glucose area under the curve in an oral glucose tolerance test) and incident type 2 diabetes in a 5-year follow-up study of a population-based cohort of Finnish men (METSIM Study, N = 1,050) having non-cholesterol sterols measured at baseline. Additionally we determined the association of 538,265 single nucleotide polymorphisms (SNP) with non-cholesterol sterol levels in a cross-sectional cohort of non-diabetic offspring of type 2 diabetes (the Kuopio cohort of the EUGENE2 Study, N = 273). We found that in a cross-sectional METSIM Study the levels of sterols indicating cholesterol absorption were reduced as a function of increasing fasting glucose levels, whereas the levels of sterols indicating cholesterol synthesis were increased as a function of increasing 2-hour glucose levels. A cholesterol synthesis marker desmosterol significantly predicted an increase, and two absorption markers (campesterol and avenasterol) a decrease in the risk of hyperglycemia and incident type 2 diabetes in a 5-year follow-up of the METSIM cohort, mainly attributable to insulin sensitivity. A SNP of ABCG8 was associated with fasting plasma glucose levels in a cross-sectional study but did not predict hyperglycemia or incident type 2 diabetes. In conclusion, the levels of some, but not all non-cholesterol sterols are markers of the worsening of hyperglycemia and type 2 diabetes.
我们研究了非胆固醇甾醇的水平作为预测高血糖（口服葡萄糖耐量试验中葡萄糖曲线下面积增加）和 2 型糖尿病发病的指标，该研究是对芬兰男性人群进行的一项基于人群的队列研究（METSIM 研究，N=1050），在基线时测量了非胆固醇甾醇。此外，我们还在非 2 型糖尿病（EUGENE2 研究的 Kuopio 队列，N=273）的 2 型糖尿病患者非糖尿病后代的横断面队列中，确定了 538265 个单核苷酸多态性（SNP）与非胆固醇甾醇水平的关联。我们发现，在横断面 METSIM 研究中，指示胆固醇吸收的甾醇水平随着空腹血糖水平的升高而降低，而指示胆固醇合成的甾醇水平随着 2 小时血糖水平的升高而升高。胆固醇合成标志物 desmosterol 显著预测了风险的增加，而两种吸收标志物（菜油固醇和avenasterol）则预测了高血糖和 2 型糖尿病发病的风险降低，这主要归因于胰岛素敏感性。ABCG8 的 SNP 与横断面研究中的空腹血浆葡萄糖水平相关，但不能预测高血糖或 2 型糖尿病的发生。总之，一些而非所有非胆固醇甾醇的水平是高血糖和 2 型糖尿病恶化的标志物。
