JCEM揭秘：糖尿病药物降低HIV患者的心脏病风险

  近日，一项刊登于国际杂志The Journal of Clinical Endocrinology & Metabolism上的研究论文中，来自华盛顿大学医学院的研究人员通过研究发现，一种糖尿病药物或可有效抑制HIV患者发生心血管问题，这种糖尿病药物或可减少和心脏疾病及中风相关的炎症反应。
  目前尽管HIV引发的感染不再是无药可治，但感染HIV的患者往往患心脏病发作和糖尿病及血糖、胰岛素和胆固醇相关疾病的风险较高，部分原因就是慢性炎症所致；而本文研究中，研究人员发现糖尿病药物西他列汀(Sitagliptin)不仅可以改善HIV成年个体的机体代谢，而且可以明显降低患者机体炎症表现。
  研究者Kevin E. Yarasheski博士表示，我们的目的就是开发出新型疗法不仅可以有效解决患者的血糖和血脂问题，而且可以降低引发心脏病和中风的炎症表现；本文研究中，研究者对36名年龄在18-65岁间的HIV病人进行了研究，这些患者均正在进行抗逆转录病毒治疗，机体的免疫系统状况较为稳定；研究初期研究者测定了患者机体的葡萄糖水平、胰岛素敏感性、脂质水平、免疫细胞计数、炎性标志物及其它健康指示器的情况。
  研究者表示，寻找治疗这些患者的疗法或许比较困难，部分是因为患者正在服用HIV药物，而这些药物在抑制患者向AIDS进展的过程中，也会和治疗HIV患者其它疾病表现的新型药物发生潜在地作用。其中一半的研究对象服用西他列汀半周，另一半进行安慰剂治疗，同时所有研究者均进行抗逆转录病毒治疗。
  研究者想知道是否西他列汀可以改善HIV患者机体的血糖问题，并且降低其炎性标志物的水平，后期他们还需要进行更多研究来确定是否8周疗法后患者机体的炎性标志物水平下降会导致患者心脏病及其它代谢性疾病风险的降低，但目前的研究结果非常有希望；研究者说道，降低血糖或者血脂或许并不行，而应该靶向作用代谢调节和免疫调节之间的关系，然而是否糖尿病特殊药物降低炎性可以导致心血管疾病、心脏病及高血压等问题得以治疗目前仍然需要更为深入的研究才能下定论。

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转化医学网推荐的原文摘要：

Sitagliptin Reduces Inflammation and Chronic Immune Cell Activation in HIV+ Adults with Impaired Glucose Tolerance
JCEM doi:10.1210/jc.2015-1531
Conor Best, Heidi Struthers, Erin Laciny, Michael Royal, Dominic N. Reeds, and Kevin E. Yarasheski
Context:
Human immunodeficiency virus (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 antiretroviral therapy (cART). The underlying mechanism(s) may involve chronic low-grade systemic inflammation and immune cell activation. Dipeptidyl peptidase-4 inhibitors (DPP4i; sitagliptin) improve glucose tolerance, and may possess immunomodulatory effects, because leukocyte CD26 cell surface receptors express DPP4 activity.
Objective.
Sitagliptin will reduce inflammatory and immune cell activation markers known to be elevated in cART-treated HIV+ adults with impaired glucose tolerance.
Design.
A prospective, randomized, placebo-controlled, double-blind trial of sitagliptin in HIV+ adults.
Setting.
Academic medical center.
Patients.
cART-treated HIV+ men and women (n=36) with stable HIV disease and impaired glucose tolerance.
Interventions.
Sitagliptin 100 mg/d or placebo for 8 weeks.
Main Outcome Measures.
At baseline and week 8, plasma hsCRP and CXCL10 concentrations (ELISA), oral glucose tolerance, and abdominal subcutaneous adipose mRNA expression for M1 macrophage markers (MCP-1, EMR1).
Results.
Sitagliptin reduced glucose area under the curve (p=0.002) and improved oral glucose insulin sensitivity index (p=0.04) more than placebo. Sitagliptin reduced plasma hsCRP and CXCL10 levels more than placebo (p<0.009). Adipose tissue MCP-1 mRNA abundance declined significantly more (p=0.01), and adipose EMR1 mRNA expression tended to decline more (p=0.19) in sitagliptin than placebo.
Conclusion.
Sitagliptin had beneficial systemic and adipose anti-inflammatory effects in cART-treated HIV+ adults with impaired glucose tolerance.
Large scale, long-term studies should determine if sitagliptin reduces cardiovascular risk and events in HIV+ adults.