胰岛素改善Ⅱ型糖尿病患者血脂?这些指标有提示!

2022/01/06 858

Ⅱ型糖尿病是一种慢性疾病,其特征是β细胞功能逐渐丧失[1]。因此,随着时间的推移,维持目标血糖水平的患者比例稳步下降,在确诊后9年,大约20%的患者需要胰岛素治疗[2-3]。



胰岛素


胰岛素会加速动脉粥样硬化,增加心血管的发生率和死亡率[4-5]。胰岛素已被证明会增加线粒体衍生的活性氧,导致血小板功能障碍[6-7]。用胰岛素使血糖控制急性正常化可以迅速改善血脂,尤其是甘油三酯(TG)[8]。


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一项实验表明,甘精胰岛素和非甘精胰岛素组的总胆固醇 (TC) 和低密度脂蛋白胆固醇 (LDL-C) 水平相似,这表明用长效胰岛素类似物进行慢性胰岛素治疗没有对脂质谱有相关影响[9]。


一项研究显示,二肽基肽酶4抑制剂(DPP4-I)、吡格列酮、胰岛素促分泌剂和阿卡波糖对血脂的影响,发现DPP4-I、阿卡波糖和吡格列酮对血脂的影响比磺脲类药物更有利[10]。在一项荟萃分析中,二甲双胍加DPP4-I或胰高血糖素样肽1受体激动剂(GLP-1RA)的双重联合治疗导致脂质谱的更大改善[11]。



胰岛素对相关指标的影响


与基础胰岛素相比,使用GLP-1RA进行治疗可更大程度地降低TC和LDL-C。胰岛素增敏剂(TZD显著改善了HDL-C,但与TC和LDL-C的增加有关。DPP4-I和标准疗法(磺脲类±二甲双胍)诱导的TC、LDL-C和HDL-C的变化与基础胰岛素观察到的变化相似。基础胰岛素在降低TG方面优于标准治疗[12]


GLP-1RA已被提议作为需要注射治疗的患者的首选。与胰岛素相比,GLP-1RA在降低HbA1c方面表现出至少相似的功效,低血糖和体重减轻的风险较低。此外,4GLP-1RA(利拉鲁肽、司美鲁肽、阿必鲁肽和度拉糖肽)能够降低Ⅱ型糖尿病患者的心血管的发生[13-14]。改善血糖控制和体重的效果,导致胰岛素抵抗改善,减少游离脂肪酸流入肝脏[15]。


使用利拉鲁肽和艾塞那肽观察到的其他可能机制可能涉及肠粘膜上的GLP-1受体信号传导,这导致含有载脂蛋白B48的乳糜微粒分泌减少,随后TG的吸收减少[16]。


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LDL-C实际上被认为是主要的脂质目标,但Ⅱ型糖尿病通常与一组代谢相关的脂质异常相关,导致TG产生增加和HDL水平降低[17]。TZD证明对通过与过氧化物酶体激活受体合介导的脂质谱产生有益影响[18]。格列酮和罗格列酮均已被证明可增加HDL-C并降低TG。然而,与吡格列酮不同的是,罗格列酮增加了TC和LDL-C[19]。



结论


综上所述,GLP-1RA在控制TC和LDL-C方面优于基础胰岛素。基础胰岛素有效降低血清TG。TZD导致HDL-C的改善,而DPP4-I和标准治疗对脂质水平没有任何显著影响。


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声明:本文为医会宝编辑部原创整理,仅代表作者个人观点,希望大家理性判断,有针对性应用。