Galantamine alleviates inflammation and insulin resistance in patients with metabolic syndrome in a randomized trial
Galantamine alleviates inflammation and insulin resistance in patients with metabolic syndrome in a randomized trial
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DOI：
10.1172/jci.insight.93340
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发表时间：
2017-07-20
期刊：
影响因子：
8
通讯作者：
Pavlov, Valentin A.
中科院分区：
文献类型：
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作者：
Consolim-Colombo, Fernanda M.;Sangaleti, Carine T.;Pavlov, Valentin A.
背景。代谢综合征（MetS）是一种肥胖驱动的流行病，可增加2型糖尿病和心血管疾病的风险。尽管炎症与MetS的发病机制有关，但病理生理机制尚不清楚。本研究的目的是评估加兰他明（一种具有抗炎特性的中枢作用乙酰胆碱酯酶抑制剂）对与胰岛素抵抗和心血管风险相关的炎症标志物以及mets受试者的其他代谢和心血管指标的影响。在这项随机、双盲、安慰剂对照的试验中，met患者（每组30人）每天口服加兰他明8毫克，持续4周，随后每天口服加兰他明16毫克，持续8周或安慰剂。主要结果是通过与MetS相关的血浆细胞因子和脂肪因子水平评估炎症。次要终点包括体重、脂肪组织储备、血糖、胰岛素、胰岛素抵抗稳态模型评估（HOMA-IR）、胆固醇（总胆固醇、HDL、LDL）、甘油三酯、血压、心率和心率变异性（HRV）。与安慰剂相比，加兰他明导致血浆中促炎分子TNF （-2.57 pg/ml [95% CI -4.96至-0.19],P = 0.035）和瘦素（-12.02 ng/ml [95% CI -17.71至-6.33],P < 0.0001）水平降低，抗炎分子脂联素（2.71 μ g/ml [95% CI 1.93至3.49],P < 0.0001）和IL-10 （1.32 pg/ml, [95% CI 0.29至2.38],P = 0.002）水平升高。加兰他明还能显著降低血浆胰岛素和HOMA-IR值，并改变心率。低剂量加兰他明可减轻MetS患者的炎症和胰岛素抵抗。这些发现支持加兰他敏在MetS治疗中的进一步研究。
BACKGROUND. Metabolic syndrome (MetS) is an obesity-driven condition of pandemic proportions that increases the risk of type 2 diabetes and cardiovascular disease. Pathophysiological mechanisms are poorly understood, though inflammation has been implicated in MetS pathogenesis. The aim of this study was to assess the effects of galantamine, a centrally acting acetylcholinesterase inhibitor with antiinflammatory properties, on markers of inflammation implicated in insulin resistance and cardiovascular risk, and other metabolic and cardiovascular indices in subjects with MetS.METHODS. In this randomized, double-blind, placebo-controlled trial, subjects with MetS (30 per group) received oral galantamine 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo. The primary outcome was inflammation assessed through plasma levels of cytokines and adipokines associated with MetS. Secondary endpoints included body weight, fat tissue depots, plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol (total, HDL, LDL), triglycerides, BP, heart rate, and heart rate variability (HRV).RESULTS. Galantamine resulted in lower plasma levels of proinflammatory molecules TNF (-2.57 pg/ml [95% CI -4.96 to -0.19]; P = 0.035) and leptin (-12.02 ng/ml [95% CI -17.71 to -6.33]; P < 0.0001), and higher levels of the antiinflammatory molecules adiponectin (2.71 mu g/ml [95% CI 1.93 to 3.49]; P < 0.0001) and IL-10 (1.32 pg/ml, [95% CI 0.29 to 2.38]; P = 0.002) as compared with placebo. Galantamine also significantly lowered plasma insulin and HOMA-IR values, and altered HRV.CONCLUSION. Low-dose galantamine alleviates inflammation and insulin resistance in MetS subjects. These findings support further study of galantamine in MetS therapy.