继发磺脲类药失效病理机制的探讨

An investigation of pathogenesis related to secondary sulphonylurea failure

目的 探讨 2型糖尿病患者继发磺脲类药 (SU )失效的发生机制。方法 利用总胰岛素原 (TPI)、完整胰岛素原 (IPI)和真胰岛素 (SI)定量检测技术 ,比较健康对照组 (n =10 )、SU有效组 (n =3 8)和继发SU失效组 (n =46)糖耐量试验 (OGTT)过程中胰岛素样激素分泌水平 (分别用曲线下面积AUCTPI、AUCIPI和AUCSI表示 )及其与血糖调节的关系 ,计算各组AUCTPI/AUCSI比和胰岛素抵抗指数 ,并用两分类Logistic回归分析筛选可能导致继发SU失效的危险因素 ,根据试验结果分析继发SU失效的发生机制。结果 两个糖尿病组空腹TPI和IPI均高于对照组 ,几何平均数(pmol/L) 分别为SU有效组 :14 9,4 1;SU失效组 :12 9,3 9;对照组 :3 2 ,0 6,差别有非常显著意义 ,所有P <0 0 0 1。糖负荷后两个糖尿病组AUCSI低于对照组 ,几何平均数分别为 (mu/L/h)SU有效组 :19 3 ;SU失效组 :2 4 6;对照组 :42 4,差别有显著意义 ,所有P≤ 0 0 1,但AUCTPI/AUCSI比高于对照组 ,几何平均数分别为SU有效组 :3 4;SU失效组 :2 3 ;对照组 :1 0 ,差别有非常显著意义 ,P均为 0 0 0 1。继发SU失效组OGTT第 3h的血糖水平 (2 2 8mmol/L)明显高于SU有效组 (19 5mmol/L) ,差别有非常显著意义 ,P =0 0 0 5,且与AUCSI无相关关系 (r=-0 15,P =0 3

Objective Probe into pathogenesis that may be responsible for secondary sulphonylurea (SU) failure. Methods Blood samples from 3 groups (10 healthy controls, 38 SU responders and 46 secondary SU failures) were taken at 5 time points during a standard oral glucose tolerance test (OGTT) and were measured for glucose, total proinsulin (TPI), intact proinsulin (IPI) and specific insulin (SI). Expressed as areas under curve (AUC) and AUCTP I/AUCS I ratio were compared between groups. Homa insulin resistant index and effect of blood glucose regulation among groups was also analyzed. Results Fasting TPI and IPI from both patient groups were markedly higher than control group ( P <0 001). Compared to con trols, AUCS I of both patient groups were significantly lower ( P ≤0 01) wh ile AUC TPI /AUC SI ratios were distinctly higher ( P <0 001). Bloo d glucose at 180 mins during OGTT was significantly higher in secondary SU failu re group ( P =0 005) remarked with no correlation to AUCS I ( r =-0 15, P =0 32). Binary logistic analysis found that elevated 3 h-glucose level w as a hazard factor for SU failure. Conclusion Type 2 diabetes h ave obvious fasting hyperproinsulinemia but distinct insulin deficiency after gl ucose challenging. SU failures have no extra insulin resistance and proinsulin c onversion machinery dysfunction. Persistent hyperglycemia may be a dominant hazard factor that was responsible for secondary SU failure.