Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221 005, India.
Acta Diabetol. 2013 Aug;50(4):511-8. doi: 10.1007/s00592-011-0307-8. Epub 2011 Jun 22.
Pancreatic beta cell dysfunction and reduced insulin sensitivity are fundamental factors associated with glucotoxicity, lipotoxicity and oxidative stress in type 2 diabetic patients (T2DM). Diabetic milieu can induce apoptosis in several types of cells. The aim of present study was to compare circulating soluble apoptotic markers (sFas and sFas-L) with HOMA-IR, HOMA-%S, HOMA-%B in the serum of newly diagnosed T2DM and healthy subjects. For this study, 94 T2DM and 60 healthy subjects were enroled and evaluated for various parameters. Biochemical quantifications were performed with Syncron CX5 auto-analyzer. The levels of serum sFas-L, TNF-α and IL-6 were estimated by flowcytometry. The fasting serum insulin and sFas quantified by ELISA. HOMA-IR, HOMA-%S and HOMA-%B were calculated with HOMA calculator v2.2.2. The levels of TC, TG, LDL-C, VLDL-C were augmented and HDL declined significantly (P < 0.001) in diabetics. The levels of serum insulin, TNF-α, IL-6, sFas, HOMA-IR were raised (P < 0.001) and sFas-L, HOMA-%S and HOMA-%B were decreased significantly (P < 0.001) in T2DM subjects than healthy. In diabetics, serum sFas was positively correlated with HOMA-IR (r = 0.720, P < 0.001) and negatively with HOMA-%B (r = -0.642, P < 0.001) significantly while serum sFasL was negatively correlated with HOMA-IR (r = -0.483, P < 0.001) and positively with HOMA-%B (r = 0.466, P < 0.001) significantly. Further, the multivariate stepwise regression analysis shows that HOMA-IR contributes significantly to the variance of sFas and sFasL. Our findings suggest that the pancreatic beta cell dysfunction along with increased insulin resistance appears to be associated with apoptotic markers.
胰腺β细胞功能障碍和胰岛素敏感性降低是与 2 型糖尿病患者（T2DM）的糖毒性、脂毒性和氧化应激相关的基本因素。糖尿病环境可诱导多种细胞凋亡。本研究旨在比较新诊断的 T2DM 患者和健康受试者血清中循环可溶性凋亡标志物（sFas 和 sFas-L）与 HOMA-IR、HOMA-%S 和 HOMA-%B 的相关性。为此，本研究纳入了 94 例 T2DM 患者和 60 例健康对照者，并对其进行了各项参数评估。生化定量采用 Syncron CX5 自动分析仪进行。通过流式细胞术检测血清 sFas-L、TNF-α 和 IL-6 水平。采用 ELISA 法检测空腹血清胰岛素和 sFas 水平。采用 HOMA 计算器 v2.2.2 计算 HOMA-IR、HOMA-%S 和 HOMA-%B。结果显示，糖尿病患者 TC、TG、LDL-C 和 VLDL-C 水平显著升高（P < 0.001），HDL 水平显著降低（P < 0.001）。与健康对照组相比，T2DM 患者血清胰岛素、TNF-α、IL-6、sFas 和 HOMA-IR 水平升高（P < 0.001），sFas-L、HOMA-%S 和 HOMA-%B 水平降低（P < 0.001）。在糖尿病患者中，血清 sFas 与 HOMA-IR 呈正相关（r = 0.720，P < 0.001），与 HOMA-%B 呈负相关（r = -0.642，P < 0.001），而血清 sFasL 与 HOMA-IR 呈负相关（r = -0.483，P < 0.001），与 HOMA-%B 呈正相关（r = 0.466，P < 0.001）。进一步的多元逐步回归分析表明，HOMA-IR 对 sFas 和 sFasL 的变化有显著贡献。本研究结果提示，胰腺β细胞功能障碍伴胰岛素抵抗增加可能与凋亡标志物有关。
