血清分泌型卷曲相关蛋白4水平与胰岛β细胞功能的相关性研究

Relationship between serum secreted Frizzled-related protein 4 and the pancreatic β cell function

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.