目的探讨不同糖耐量状态下分泌型卷曲相关蛋白4(SFRP4)与胰岛β细胞第一时相分泌功能的关系。方法新诊断2型糖尿病患者56例(T2DM组);糖耐量受损52例(IGT组);正常对照者42名(NGT组)。行静脉葡萄糖耐量试验,ELISA法测定空腹血清SFRP4及白细胞介素(IL)-1β水平。计算急性胰岛素分泌反应(AIR)、第一时相(0-10min)胰岛素分泌曲线下面积(AUC)、葡萄糖处置指数(GDI)、稳态模型评估的胰岛β细胞功能指数(HOMA—β)及胰岛素抵抗指数(HOMA—IR)。探讨SFRP4与AIR、AUC、GDI、HOMA—IR、HOMA—β的关系。结果(1)T2DM组和IGT组血清SFRP4水平显著高于NGT组[(184.38±61.34和141.64±40.46对95.46±20.13)ng/ml,P〈0.01];T2DM组和IGT组AIR、AUC、GDI显著低于NGT组(P〈0.01),且在T2DM组最低;(2)SFRP4与HOMA—β、AIR、AUC、GDI呈显著负相关(P〈0.01),与空腹血糖、餐后2h血糖、HbA1C、IL-1β、超敏C反应蛋白呈正相关(P〈0.01);(3)多元逐步回归分析显示,AUC、HOMA—IR、血清IL-1β水平是SFRP4的独立影响因素。结论血清SFRP4水平与糖代谢状态密切相关,且与胰岛β细胞第一时相分泌功能及慢性低度炎症反应有关,SFRP4可能参与2型糖尿病的发生发展。
Objective To investigate the relationship between serum secreted frizzled-related protein 4 ( SFRP4 ) and the first-phase of glucose-stimulated insulin secretion from pancreatic β cell under different glucose tolerance statuses. Methods Fifty-six patients with newly diagnosed type 2 diabetes mellitus ( T2DM group) , 52 patients with impaired glucose tolerance ( IGT group ) , and 42 subjects with normal glucose tolerance ( NGT group ) underwent intravenous glucose tolerance test. Fasting serum SFRP4 and interleukin (IL)-1β were 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 calculated. Results ( 1 ) The levels of SFRP4 and IL-1β in T2DM group and IGT group were significantly higher than that in NGT group [ ( 184.38± 61.34 or 141.64 ±40.46 or 95.46 ± 20.β ) ng/ml, P〈0.01 ]. AIR, AUC, and GDI in T2DM group and IGT group were significantly lower than those in NGT group ( P〈0.01 ) , and these results were more significantly reduced in T2DM group compared with those in IGT group. (2) SFRP4 was negatively correlated with AIR, AUC, GDI, HOMA-β (P〈0.01), and positively correlated with fasting plasma glucose, 2 h plasma glucose after glucose loading, HbA1c, IL-1β, and high sensitive C-reactive protein ( P〈0.01 ). (3) Multiple stepwise regression analysis showed that AUC, HOMA-IR, and serum IL-1β level were independently associated with SFRP4. Conclusion The concentration of serum SFRP4 is closely correlated with the glycolipid metabolic disorder, the first-phase of glucose-stimulated insulin secretion, and chronic low-grade inflammation. SFRP4 may be involved in the mechanism of β cell dysfunction in type 2 diabetes mellitus.