Brain:DPP4抑制剂使糖尿病帕金森病患者长期获益

2021-06-07 MedSci原创 MedSci原创

DPP4抑制剂可能对糖尿病帕金森病患者的基线黑质多巴胺变性和长期运动结果产生有益影响

二肽基肽酶-4抑制剂或称DPP-4 抑制剂或列汀类药物,是一种通过抑制二肽基肽酶-4来发挥作用的口服抗糖尿病药,主要用来治疗2型糖尿病(T2DM)。第一种DPP-4抑制剂是西格列汀,于2006年通过了美国食品药品监督管理局(USFDA)的审批.

胰高血糖素提高血糖水平,DPP-4抑制剂可以减少胰高血糖素和降低血糖水平。DPP-4抑制剂的原理为增加可以抑制胰高血糖素释放的肠促胰岛素激素的水平(GLP-1)和GIP,增加胰岛素分泌,减慢胃排空,降低血糖水平。

对于大多数T2DM患者,DPP-4抑制剂不作为初始治疗,而应从饮食调整、减重、运动及使用二甲双胍(如无禁忌证)入手。DPP-4抑制剂可作为单药治疗,用于不能耐受或禁用二甲双胍的患者,例如合并慢性肾病,特别是低血糖风险特别高的患者。

帕金森病(PD)是世界上第二大神经退行性疾病,其特征是运动迟缓、肢体僵硬和震颤。PD患者还可能有认知和行为问题,例如痴呆症在病情严重的患者中相当常见,超过三分之一的病例也会发生重性抑郁障碍和焦虑症。其它可能伴随的症状包括知觉、睡眠、情绪问题。

有研究显示,那些患有T2DM的人患后期发展为逐渐衰弱的神经系统疾病的风险增加了32%。更有数据提示,帕金森病或许与T2DM有着共同的发病机制。那么,DPP4抑制剂的治疗是否对患PD的糖尿病患者的黑质多巴胺和纵向运动表现产生有益影响呢?为此,来自韩国延世大学医学院神经学系的专家开展了相关研究,结果发表在Brain杂志上。

研究人员将697名接受了多巴胺转运体成像的新发PD患者根据先前的糖尿病诊断和DPP4抑制剂的使用情况分为三组:正在接受DPP4抑制剂治疗的PD糖尿病患者(组1,n = 54)或不使用DPP4抑制剂的帕金森病患者(组2, n = 85),以及非糖尿病的帕金森病患者(组3,n = 558)。

接受DPP4抑制剂治疗的PD糖尿病患者在壳核前部(2.56±0.74 vs 2.10±0.50;P=0. 016)、后部(1.83±0.69 vs 1.40±0.50;P<0.001)和腹侧(1.72±0.58 vs 1.35±0.37;P=0.001)基础多巴胺水平均比非DPP4抑制剂治疗的PD糖尿病患者高。此外,正在接受DPP4抑制剂治疗的PD糖尿病患者在后壳核的多巴胺转运体可用性高于非糖尿病帕金森病患者(1.83 ± 0.69 vs 1.43 ± 0.59;P < 0.001)。

在调整了年龄、性别、病程和血管危险因素后,线性回归模型显示,先前的DPP4抑制剂治疗仍与壳核前部(β = -0. 186,P = 0.012)、后部(β = -0.336,P < 0.001)和腹侧(β = -0.204,P = 0.005)多巴胺转运体的可用性有独立和显著的关系。

线性混合模型显示,正在接受DPP4抑制剂治疗的帕金森病糖尿病组的左旋多巴当量的纵向增加比其他组慢。生存分析显示,先前用DPP4抑制剂治疗的糖尿病组的左旋多巴诱发运动障碍的比率明显低于没有DPP4抑制剂的糖尿病组。

这些发现表明,DPP4抑制剂可能对糖尿病帕金森病患者的基线黑质多巴胺变性和长期运动结果产生有益影响,并可能将其作用扩展到非糖尿病帕金森病患者。

 

参考文献:

Beneficial effects of dipeptidyl peptidase-4 inhibitors in diabetic Parkinson’s disease, Brain, Volume 144, Issue 4, April 2021, Pages 1127–1137, https://doi.org/10.1093/brain/awab015

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    2022-05-19 jklm09
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    2021-06-09 oliver176
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    2021-06-08 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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拓展阅读

Int J Endocrinol:DPP4抑制剂对2型糖尿病患者认知功能障碍的影响

DPP4抑制剂可显著改善2型糖尿病患者的认知功能障碍,降低空腹血糖、餐后2小时血糖和糖化血红蛋白。

SGLT2I和DPP4I哪家强?中国香港研究:在2型糖尿病患者抗OAD发生和加重上,SGLT2I更有优势!

JAMA Netw Open:钠-葡萄糖共转运体2抑制剂与二肽基肽酶-4抑制剂使用与香港2型糖尿病患者发生阻塞性气道疾病和加重事件风险的关系

Hypertension:注意了——DPP4抑制剂和ACEI联用易出现这种副作用!

在同时进行ACEI和DPP4抑制剂时,儿茶酚胺的增加可能导致易患心力衰竭的患者出现心血管并发症。

Diabetes Obes Metab:SGLT2抑制剂与DPP4抑制剂治疗患者心衰风险比较

与使用DPP4抑制剂的老年人相比,使用SGLT2抑制剂的老年人心衰住院或死亡的发生率较低,且低血糖发生率较低,但糖尿病酮症酸中毒的发生率增加。

DIABETOLOGIA:西格列汀对前驱糖尿病患者能量代谢和棕色脂肪组织的影响

这项研究的目的是评估西他列汀对前驱糖尿病患者(葡萄糖耐量降低和体重过重)的超重个体的葡萄糖耐量,血脂,能量消耗和棕色脂肪组织(BAT),白色脂肪组织(WAT)和骨骼肌代谢的代谢的影响。 研究人员对莱顿大学医学中心和Alrijne医院的30名超重欧洲男性(年龄45.9±6.2岁; BMI 28.8±2.3 kg / m 2)进行了随机,双盲,安慰剂对照试验。 使用由非盲法药剂师建立的