GLP-1受体激动剂对锌-α2-糖蛋白的影响及其与胰岛素抵抗关系

Effects of GLP-1 receptor agonist on Zinc-α2-glycoprotein and its relationship with insulin resistance in patients with newly diagnosed type 2 diabetes

目的:阐明锌-α2-糖蛋白(Zinc-α2-glycoprotein,ZAG)与胰岛素抵抗的关系以及胰升糖素样肽1(glucagon-like peptide-1,GLP-1)受体激动剂治疗的影响。方法:新发2型糖尿病(newly diagnosed T2DM,n T2DM)患者120例随机分为利拉鲁肽组(n=45,利拉鲁肽0.6~1.8 mg,i H qd)、利拉鲁肽+二甲双胍组(n=45,利拉鲁肽0.6~1.8 mg,i H qd+二甲双胍0.5g bid)、安慰剂组(n=30,生理盐水150μl i H qd+二甲双胍0.5g bid),治疗12周,同期选取年龄、性别相匹配的健康体检者作为健康对照组(n=30)。治疗前后分别行75g OGTT、胰岛素钳夹试验并检测血浆ZAG、脂联素(adiponectin,ADI)水平及相关代谢指标。结果:n T2DM患者基础血浆ZAG水平明显低于健康对照组(P<0.01),通过利拉鲁肽、利拉鲁肽+二甲双胍治疗后12周,患者的糖化血红蛋白,空腹血糖,糖负荷后2 h血糖,甘油三酯和稳态模型评估胰岛素抵抗指数均较治疗前明显下降(P<0.05),通过安慰剂治疗后上述指标明显高于利拉鲁肽治疗组(P<0.05);而在钳夹过程中,M值明显升高(P<0.01)。此外,与治疗前相比,利拉鲁肽治疗后血浆ZAG、ADI水平明显增加(P<0.01)。结论:n T2DM患者经GLP-1受体激动剂治疗后,糖代谢及胰岛素敏感性得到明显改善,血浆ZAG水平也明显升高,提示ZAG将可能被作为代谢综合征或者T2DM的一个新的生物标志物。

Objective:To illuminate the relation of Zinc-α2-glycoprotein(ZAG)and insulin resistance(IR)in patients with newly diagnosed type 2 diabetes(n T2DM),and to examine the effect of glucagon-like peptide-1(GLP-1) receptor agonist on ZAG and adiponectin(ADI). Methods:Totally 120 subjects with n T2 DM were assigned randomly to receive placebo(normal saline+metformin)or liraglutide,or metformin + liraglutide for 12 weeks. Before and after the treatment,subjects received 75 g OGTT,euglycemic-hyperinsulinemic clamp(EHCs),and measurement of metabolic index,serum ZAG and ADI concentrations. Results:Circulating ZAG was significantly lower in n T2 DM than in normal individuals(P<0.01). After 12 weeks of liraglutide or metformin + liraglutide,glycosylated hemoglobin(Hb A1c),fasting blood glucose(FBG),oral glucose tolerance test 2 hour blood glucose(2h BG),triglycerides(TG)and HOMA-IR were decreased significantly compared with those of pre- treatment(P < 0. 05),whereas M values during EHCs were significantly increased(P <0.01). Importantly,after the treatment with liraglutide,circulating ZAG and ADI concentrations were significantly increased along with improved glucose metabolism and insulin sensitivity compared with those of pre-treatment(both P<0.01). Conclusion:Circulating ZAG level,insulin resistance and glucolipid metabolism are significantly increased after with liraglutide treatment. ZAG can be used as a novel biomarker for metabolic syndrome and T2 DM.