The increased dipeptidyl peptidase-4 activity is not counteracted by optimized glucose control in type 2 diabetes, but is lower in metformin-treated patients
The increased dipeptidyl peptidase-4 activity is not counteracted by optimized glucose control in type 2 diabetes, but is lower in metformin-treated patients
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DOI：
10.1111/j.1463-1326.2011.01550.x
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发表时间：
2012-06-01
影响因子：
5.8
通讯作者：
Avogaro, A.
中科院分区：
文献类型：
--
作者：
Fadini, G. P.;Albiero, M.;Avogaro, A.
目的：二肽基肽酶（DPP）-4负责肠促胰岛素降解，一些观察结果表明，DPP-4活性在2型糖尿病（T2 D）中升高。我们旨在评估T2 D和血糖控制对DPP-4活性的影响。方法：在第一组（SET 1）患者中，我们比较了30例T2 D和20例年龄和性别匹配的非糖尿病受试者的血浆DPP-4活性。在第二组（SET 2）中，我们在42例T2 D患者中测量了通过添加基础胰岛素治疗实现血糖控制试验（NCT 00699686）前后的血清DPP-4活性。使用显色和荧光底物以及几种阳性和阴性对照品测定血清/血浆DPP-4活性。结果：在SET 1中，T2 D患者血浆DPP-4活性显著高于对照组（32.2 ± 1.2 U/ l vs. 21.2 ± 1.1 U/ l，p < 10-6）。通过对文献的荟萃分析，我们发现与对照组相比，T2 D与DPP-4活性增加33%相关。在SET 2中，尽管血红蛋白A1 c（HbA 1c）平均降低1.5%，但强化血糖控制并未降低血清DPP-4活性。在两组糖尿病患者中，使用二甲双胍与DPP-4活性显著降低相关，与年龄、性别、体重指数和HbA 1c无关。结论：T2 D患者的DPP-4活性增加，但血糖控制不会降低，表明高血糖不是DPP-4活性的直接决定因素。然而，二甲双胍可能间接降低DPP-4活性。
Aim: Dipeptidyl peptidase (DPP)-4 in responsible for incretin degradation and some observations suggest that DPP-4 activity is increased in type 2 diabetes (T2D). We aimed to assess the effect of T2D and glucose control on DPP-4 activity. Methods: In the first set (SET1) of patients, we compared plasma DPP-4 activity between 30 T2D and 20 age-and sex-matched non-diabetic subjects. In the second set (SET2), we measured serum DPP-4 activity in 42 T2D patients before and after a trial of glucose control achieved by add-on basal insulin therapy (NCT00699686). Serum/ plasma DPP-4 activity was determined using chromogenic and fluorigenic substrates, as well as several positive and negative controls. Results: In SET1, plasma DPP-4 activity was significantly higher in T2D vs. controls (32.2 + 1.2 U/ l vs. 21.2 + 1.1 U/ l, p < 10-6). From a meta-analysis of the literature, we found that T2D is associated with a 33% increase in DPP-4 activity compared to controls. In SET2, serum DPP-4 activity was not lowered by intensified glucose control, despite an average haemoglobin A1c (HbA1c) reduction of 1.5%. In both sets of diabetic patients, the use of metformin was associated with a significantly lower DPP-4 activity, independently of age, sex, body mass index and HbA1c. Conclusion: DPP-4 activity is increased in T2D, but is not lowered by glucose control, suggesting that hyperglycaemia is not a direct determinant of DPP-4 activity. However, metformin may indirectly reduce DPP-4 activity.