Sitagliptin Reduces Inflammation and Chronic Immune Cell Activation in HIV plus Adults With Impaired Glucose Tolerance
Sitagliptin Reduces Inflammation and Chronic Immune Cell Activation in HIV plus Adults With Impaired Glucose Tolerance
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西格列汀可减轻患有葡萄糖耐量受损的成年艾滋病病毒感染者的炎症以及慢性免疫细胞活化。
DOI：
10.1210/jc.2015-1531
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发表时间：
2015-07-01
影响因子：
5.8
通讯作者：
Yarasheski, Kevin E.
中科院分区：
文献类型：
--
作者：
Best, Conor;Struthers, Heidi;Yarasheski, Kevin E.
内容：尽管联合抗逆转录病毒治疗（cART）有效，但HIV感染与空腹高胰岛素血症、葡萄糖耐量受损的风险较高以及血管疾病、心肌梗死或卒中的发生率较高相关。潜在机制可能涉及慢性低度全身性炎症和免疫细胞活化。二肽基肽酶-4抑制剂（西格列汀）改善葡萄糖耐量，并可能具有免疫调节作用，因为白细胞CD 26细胞表面受体表达二肽基肽酶-4活性。目的：西格列汀将减少炎症和免疫细胞活化标志物，已知这些标志物在cART治疗的HIV感染（HIV +）成人葡萄糖耐量受损患者中升高。设计：这是一项西格列汀在HIV阳性成人中的前瞻性、随机、安慰剂对照、双盲试验。患者为接受cART治疗的HIV阳性男性和女性（n = 36），HIV疾病稳定且糖耐量受损。干预措施：干预措施包括西格列汀100 mg/d或安慰剂，持续8周。在基线和第8周，血浆高敏C反应蛋白和C-X-C基序趋化因子10浓度（ELISA）、口服葡萄糖耐量和腹部皮下脂肪M1巨噬细胞标志物mRNA表达（单核细胞趋化蛋白-1，含EGF样模块，粘蛋白样激素受体1）。西格列汀降低血糖曲线下面积（P = 0.002）和改善口服葡萄糖胰岛素敏感性指数（P = 0.04）比安慰剂。西格列汀降低血浆高敏C反应蛋白和C-X-C基序趋化因子10水平的作用大于安慰剂（P = 0.009）。与安慰剂相比，西格列汀组脂肪组织单核细胞趋化蛋白-1mRNA丰度下降幅度更大（P = 0.01），脂肪含EGF样模块、粘蛋白样激素受体1 mRNA表达下降幅度更大（P = 0.19）。结论：西格列汀对接受cART治疗的HIV+成人糖耐量受损患者具有有益的全身和脂肪抗炎作用。大规模、长期研究应确定西格列汀是否能降低HIV阳性成人的心血管风险和事件。
Context: HIV infection is associated with a greater risk for fasting hyperinsulinemia, impaired glucose tolerance, and higher incidence rates for vascular disease, myocardial infarction, or stroke despite effective combination antiretroviral therapy (cART). The underlying mechanism(s) may involve chronic low-grade systemic inflammation and immune cell activation. Dipeptidyl peptidase-4 inhibitors (sitagliptin) improve glucose tolerance and may possess immunomodulatory effects because leukocyte CD26 cell surface receptors express dipeptidyl peptidase-4 activity.Objective: Sitagliptin will reduce inflammatory and immune cell activation markers known to be elevated in cART-treated HIV-infected (HIV +) adults with impaired glucose tolerance.Design: This was designed as a prospective, randomized, placebo-controlled, double-blind trial of sitagliptin in HIV + adults.Setting: The setting was an academic medical center.Patients: Patients were cART-treated HIV+ men and women (n = 36) with stable HIV disease and impaired glucose tolerance.Interventions: Interventions included sitagliptin 100 mg/d or placebo for 8 weeks.Main Outcome Measures: At baseline and week 8, plasma high-sensitivity C-reactive protein and C-X-C motif chemokine 10 concentrations (ELISA), oral glucose tolerance, and abdominal sc adipose mRNAexpression for M1 macrophage markers (monocyte chemotactic protein-1, EGF-like modulecontaining, mucin-like hormone receptor 1).Results: Sitagliptin reduced glucose area under the curve (P =.002) and improved oral glucose insulin sensitivity index (P =.04) more than placebo. Sitagliptin reduced plasma high-sensitivity C-reactive protein and C-X-C motif chemokine 10 levels more than placebo (P =.009). Adipose tissue monocyte chemotactic protein-1mRNAabundance declined significantly more (P =.01), and adipose EGF-like module-containing, mucin-like hormone receptor 1 mRNA expression tended to decline more (P =.19) in sitagliptin than placebo.Conclusion: Sitagliptin had beneficial systemic and adipose anti-inflammatory effects in cARTtreated HIV+ adults with impaired glucose tolerance. Large-scale, long-term studies should determine whether sitagliptin reduces cardiovascular riskandevents in HIV+ adults.