Scheen André J, Paquot Nicolas
Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Sart Tilman (B35), University of Liège, B 4000 Liège, Belgium.
Best Pract Res Clin Endocrinol Metab. 2009 Feb;23(1):103-16. doi: 10.1016/j.beem.2008.09.001.
Abdominal obesity is associated with numerous metabolic abnormalities, including insulin resistance, impaired glucose tolerance/type-2 diabetes, and atherogenic dyslipidaemia with low high-density lipoprotein (HDL) cholesterol, high triglycerides, and increased small dense low-density lipoprotein (LDL) cholesterol. A proportion of these metabolic disorders may be attributed to increased endocannabinoid activity. The selective cannabinoid 1 (CB1) receptor antagonist rimonabant has been shown to reduce body weight, waist circumference, insulin resistance, triglycerides, dense LDL, C-reactive protein (CRP), and blood pressure, and to increase HDL and adiponectin concentrations in both non-diabetic and diabetic overweight/obese patients. Besides an improvement in glucose tolerance in non-diabetic subjects, a reduction of 0.5-0.7% in haemoglobin A1C (HbA(1c)) levels was consistently observed in various groups of patients with type-2 diabetes. Almost half the metabolic changes could not be explained by weight loss, supporting direct peripheral effects of rimonabant. Ongoing studies should demonstrate whether improved metabolic disorders with CB1 receptor antagonists (rimonabant, taranabant, etc.) would translate into fewer cardiovascular complications among high-risk individuals.
腹部肥胖与多种代谢异常相关，包括胰岛素抵抗、糖耐量受损/2型糖尿病，以及致动脉粥样硬化性血脂异常，即高密度脂蛋白（HDL）胆固醇水平低、甘油三酯水平高和小而密低密度脂蛋白（LDL）胆固醇增加。这些代谢紊乱部分可能归因于内源性大麻素活性增加。选择性大麻素1（CB1）受体拮抗剂利莫那班已被证明可减轻非糖尿病和糖尿病超重/肥胖患者的体重、腰围、胰岛素抵抗、甘油三酯、致密LDL、C反应蛋白（CRP）和血压，并提高HDL和脂联素浓度。除了改善非糖尿病受试者的糖耐量外，在各类2型糖尿病患者中还持续观察到糖化血红蛋白（HbA1c）水平降低0.5 - 0.7%。几乎一半的代谢变化无法用体重减轻来解释，这支持了利莫那班的直接外周作用。正在进行的研究应能证明，使用CB1受体拮抗剂（利莫那班、塔那那班等）改善代谢紊乱是否会减少高危个体的心血管并发症。
