加用格列美脲改善次大剂量胰岛素控制不佳的2型糖尿病胰岛素的敏感性

目的 观察病史10年以上的2型糖尿病患者应用次大剂量的胰岛素联合非促泌剂治疗,血糖仍然控制不佳的情况下加用格列美脲对血糖控制和改善胰岛素敏感性的作用,并探讨格列美脲改善胰岛素抵抗的机制.方法 采用前瞻性病例对照研究,将75例胰岛素联合非促泌剂血糖控制不佳的2型糖尿病患者随机分为原方案组(胰岛素组)和加用格列美脲组(胰岛素+格列美脲组),胰岛素组根据血糖情况继续加用胰岛素剂量至血糖控制理想,胰岛素+格列美脲组在原方案的基础上加用格列美脲,根据血糖情况调整胰岛素和格列美脲的剂量.比较治疗24周前后两组空腹血糖、餐后2 h血糖和HbA1C变化、空腹C肽、空腹胰岛素、胰岛素日剂量、低血糖事件、体重、血脂、超敏C反应蛋白(hs-CRP)、稳态模型评估的胰岛素抵抗指数(HOMA-IR)和血浆游离脂肪酸、脂联素和肿瘤坏死因子α的变化.结果 治疗前后,两组空腹C肽无明显差异,胰岛素+格列美脲组血糖控制明显好于胰岛素组,胰岛素日剂量明显降低,体重低于胰岛素组,两组间低血糖事件无差异(P＜0.05);胰岛素+格列美脲组hs-CRP明显降低(P＜0.05);两组对血脂的影响无差异;胰岛素+格列美脲组空腹胰岛素、游离脂肪酸、肿瘤坏死因子α、hs-CRP和HOMA-IR明显低于胰岛素组,脂联素高于胰岛素组(P＜0.05).结论 胰岛素联合非促泌剂血糖控制不佳的2型糖尿病患者加用格列美脲后胰岛素日剂量明显降低,在不增加低血糖的前提下持续改善患者的血糖控制,通过升高血浆脂联素和降低肿瘤坏死因子α,游离脂肪酸水平明显改善胰岛素抵抗.

Improvement of insulin sensitivity by adding on glimepiride in type 2 diabetes patients poorly controlled with sub-maximal insulin dose

Objective To observe the effect of adding on glimepiride in treating type 2 diabetic patients who had suffered the disease for more than 10 years and were poorly controlled with insulin combined with nonsulfonylureas drugs. Methods Seventy-five type 2 diabetic patients poorly controlled with insulin combined with non-sulfonylureas drugs were randomly divided into glimepiride-added group (INS+GM, n = 39 )and continuation of insulin group ( INS, n = 35 ). HbA1c, plasma glucose, daily insulin dose, number of hypoglycemic events, body weight, plasma lipid concentration,and high-sensitive C-reactive protein (hs-CRP)were recorded at weeks 0, 12,and 24. The levels of plasma free fatty acid ( FFA), adiponectin, and tumor necrosis factor-α ( TNF-α ) were measured before and 24 weeks after the therapy. Results At 12 and 24 weeks, fasting blood glucose, 2 h postprandial blood glucose,and HbA1c were improved in INS+GM group more markedly than in INS group, and daily insulin dose and body weight were decreased in INS+GM compared with INS ( P＜0. 05 ). The number of hypoglycemic events and plasma lipid concentration did not differ between two groups ( P＜0.05 ). The levels of plasma FFA,TNF-α,hs-CRP, and HOMA-IR were lower in INS+GM than INS ( P＜0.05 ), the adiponectin was higher in INS + GM than INS ( P ＜ 0.05 ). Conclusion Adding glimepiride to insulin therapy resulted in a sustained better glycemic control with less insulin daily dose, decresed body weight, and no increase in hypoglycemic events as compared with the continuing insulin therapy group. Increased adiponectin, as well as decreased plasma FFA and TNF-α may underlie the improvement of insulin resistance with glimepiride treatment.