Effects of sitagliptin on circulating zinc-α2-glycoprotein levels in newly diagnosed type 2 diabetes patients: a randomized trial
Effects of sitagliptin on circulating zinc-α2-glycoprotein levels in newly diagnosed type 2 diabetes patients: a randomized trial
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DOI：
10.1530/eje-15-0637
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发表时间：
2016-02-01
影响因子：
5.8
通讯作者：
Yang, Gangyi
中科院分区：
文献类型：
--
作者：
Tian, Mingyuan;Liang, Zerong;Yang, Gangyi
目的：锌-α（2）-糖蛋白（ZAG）是近年来发现的一种有效的代谢调节剂。然而，抗糖尿病药物对人体循环ZAG水平的影响在很大程度上仍然未知。为了探讨二肽基肽酶-IV（DPP-IV）抑制剂改善胰岛素抵抗的可能机制，我们研究了西格列汀，DPP-IV抑制剂，对新诊断的2型糖尿病（nT 2DM）patients.Design和方法循环细胞因子水平的影响：141例nT 2DM受试者的一个子集被分配接受安慰剂（n=47）或西格列汀（n=94）3个月。结果：nT 2DM患者外周血ZAG水平明显低于对照组（P< 0.01），血清脂联素（ADI）水平明显低于对照组（P< 0.01）。西格列汀治疗3个月后，HbA 1c、空腹血糖、餐后血糖、糖负荷后2小时胰岛素、甘油三酯和胰岛素抵抗稳态模型评估（HOMA-IR）较治疗前显著降低（P< 0.05或P< 0.01），而EHC时钳夹稳定期葡萄糖输注率（M值）显著增加（P< 0.01）。与治疗前相比，随着糖代谢和胰岛素敏感性的改善，循环ZAG和ADI浓度沿着显著升高（均P< 0.01），ZAG变化（Δ ZAG）与Δ ADI、Δ HOMA-IR、Δ BMI、Δ空腹胰岛素呈正相关，与Δ肿瘤坏死因子-α（TNF-α）呈负相关。结论：低水平的循环ZAG与胰岛素抵抗相关，西格列汀治疗可显著提高循环ZAG水平。这些观察结果与DPP-IV抑制剂作为胰岛素增敏剂的作用模式有关。
Objective: Zinc-alpha(2)-glycoprotein (ZAG) has recently been characterized as a potent metabolic regulator. However, the effects of anti-diabetic agents on circulating ZAG levels in humans remain largely unknown. To explore the possible mechanisms by which the dipeptidyl peptidase-IV (DPP-IV) inhibitor improves insulin resistance, we investigated the effect of sitagliptin, a DPP-IV inhibitor, on circulating cytokine levels in newly diagnosed type 2 diabetes (nT2DM) patients.Design and methods: A subset of 141 subjects with nT2DM were assigned to receive placebo (n=47) or sitagliptin (n=94) for 3 months. Before and after treatment, subjects received a 75 g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp (EHC), and measurement of ZAG and adiponectin (ADI) concentrations.Results: Circulating ZAG levels were lower in nT2DM than in control individuals (P< 0.01). After 3 months of sitagliptin treatment, HbA1c, fasting plasma glucose, postprandial glucose, 2-h insulin after glucose overload, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR) were decreased significantly compared with pre-treatment (P< 0.05 or P< 0.01), whereas the glucose infusion rate during the stable period of the clamp (M values) during EHC were significantly increased (P< 0.01). In addition, circulating ZAG and ADI concentrations were significantly increased along with improved glucose metabolism and insulin sensitivity compared with pre-treatment (both P< 0.01) and the change of ZAG (Delta ZAG) was positively associated with Delta ADI, Delta HOMA-IR, Delta BMI, Delta fasting insulin and negatively associated with Delta tumor necrosis factor-alpha (TNF-alpha). Furthermore, sitagliptin treatment resulted in significantly lowered plasma TNF-alpha level (P< 0.05).Conclusion: A low level of circulating ZAG is associated with insulin resistance and sitagliptin treatment significantly increases circulating ZAG levels. These observations have implications in relation to the mode of action of the DPP-IV inhibitor as an insulin sensitizing agent.