摘要目的 探究不同糖耐量状态下循环血裂缝诱导配体2(slit2)的表达,及其与糖尿病前期和2型糖尿病的相关性及潜在的影响因素.方法 纳入2017年6月至12月于陆军军医大学第二附属医院内分泌科就诊者143名为研究对象,其中新诊断2型糖尿病患者51例(T2DM组,男27例,女24例),糖尿病前期患者39例(pre-DM组,男15例,女24例),正常糖耐量对照组53名(NGT组,男18例,女35例).收集临床资料,行静脉葡萄糖耐量试验,ELISA法测定空腹血浆slit2水平.计算急性胰岛素分泌反应(AIR)、第一时相(0~10 min)胰岛素分泌曲线下面积(AUC)、葡萄糖处置指数(GDI)、稳态模型胰岛β细胞功能指数及稳态模型胰岛素抵抗指数(HOMA-IR).采用Spearman相关、偏相关及多元逻辑回归分析进行统计学分析.结果 (1)T2DM组和pre-DM组血浆slit2水平显著高于NGT组[分别为(2.9±2.2)、(3.0±2.8)比(1.6±1.3)μg/L,t=3.45、3.35,均P<0.01];(2)slit2与体质指数、腰围、空腹血糖、餐后2 h血糖、糖化血红蛋白、空腹胰岛素、HOMA-IR、甘油三酯呈显著正相关(r=0.174~0.389,均P<0.05),与AUC、AIR、GDI呈显著负相关(r=-0.485~-0.438,P<0.01);(3)多元逻辑回归分析显示,分别校正HOMA-IR、AUC、AIR和GDI后,slit2与2型糖尿病之间的关系消失(OR=0.857~4.482,P>0.05).结论 循环血slit2水平在糖尿病前期及2型糖尿病患者中显著升高,其与2型糖尿病的关系受胰岛素抵抗和第一时相胰岛β细胞分泌功能的影响.Slit2有望成为预测糖耐量状态的指标,并可能参与2型糖尿病的病理生理过程.

abstractsObjective To investigate the relationship among plasma slit guidance ligand 2 (slit2) and pre-diabetes and type 2 diabetes mellitus (T2DM). Methods A total of 143 subjects recruited in Department of Endocrinology of Xinqiao Hospital from Jun 2017 to Dec 2017, 51 patients diagnosed with newly T2DM(T2DM group,27 male,24 female),39 patients diagnosed with pre-diabetes(pre-DM group,15 male,24 female),and 53 subjects diagnosed with normal glucose tolerance(NGT group,18 male,35 female). Clinical data were collected,intravenous glucose tolerance test were examined and fasting plasma slit2 was assayed by ELISA. Acute insulin response (AIR), the area under the curve of the first-phase (0-10 min) insulin secretion(AUC),glucose disposition index(GDI),homeostasis model assessment for β cell function index(HOMA-β),and insulin resistance index(HOMA-IR)were measured.Results (1)The levels of slit2 in T2DM group and pre-DM group were significantly higher than those in NGT group respectively [(2.9 ± 2.2),(3.0±2.8)vs(1.6±1.3)μg/L,t=3.45,3.35,both P<0.01].(2)Slit2 was positively correlated with body mass index, waist circumference, fasting plasma glucose, 2 h plasma glucose, glycated hemoglobin A1c, fasting insulin, HOMA-IR and triglycerides (r=0.174-0.389,all P<0.05), and negatively correlated with AUC, AIR, GDI (r=-0.485--0.438,all P<0.01). (3) Multiple logistic regression analysis did not show the relationship between slit2 and T2DM after HOMA-IR,AIR,AUC and GDI were corrected respectively(OR=0.857-4.482,P>0.05).Conclusion The concentrations of plasma slit2 are closely correlated with glycol metabolism status which increased in patients with pre-diabetes and type 2 diabetes. The association between slit2 and diabetes is affected by insulin resistance and the first-phase of glucose-stimulated pancreatic β-cell function.Slit2 may be proposed as an indicator for glucose tolerance status,and it may be involved in the mechanism of type 2 diabetes mellitus.