遗传变异在大麻素受体基因（CNR1）（G1359A 多态性）对 2 型糖尿病肥胖患者接受利拉鲁肽治疗后的体重减轻和心血管危险因素的作用。

Role of genetic variation in the cannabinoid receptor gene (CNR1) (G1359A polymorphism) on weight loss and cardiovascular risk factors after liraglutide treatment in obese patients with diabetes mellitus type 2.

机构信息

From the Center of Investigation of endocrinology and Nutrition, Medicine School and Unit of Investigation, Hospital Rio Hortega, University of Valladolid, Valladolid, Spain.

出版信息

J Investig Med. 2014 Feb;62(2):324-7. doi: 10.2310/JIM.0000000000000032.

DOI:10.2310/JIM.0000000000000032

PMID:24322329

Abstract

BACKGROUND

A polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene was reported as a common polymorphism (rs1049353) with potential implications in weight loss. We decide to investigate the role of this polymorphism on metabolic changes and weight loss secondary to treatment with liraglutide.

METHODS

A population of 86 patients with diabetes mellitus type 2 and obesity, unable to achieve glycemic control (hemoglobine glycate A1c >7%) with metformin alone or associated to sulfonylurea, who require initiation of liraglutide treatment in progressive dose to 1.8 mg/d subcutaneously, was analyzed.

RESULTS

Fifty-one patients (59.3%) had the genotype G1359G, and 35 patients (40.7%) had G1359A (28 patients, 32.6%) or A1359A (7 patients, 8.1%) (A allele carriers). In patients with both genotypes, basal glucose, HbA1c, body mass index, weight, fat mass, waist circumference, and systolic blood pressures decreased. In patients with G1359G genotype, total cholesterol and low-density lipoprotein cholesterol decreased, and in patients with A allele, homeostasis model assessment for insulin resistance decreased, too.

CONCLUSIONS

There is an association of the A allele with an improvement of insulin resistance secondary to weight loss after liraglutide treatment in obese patients with diabetes mellitus type 2. Noncarriers of A allele showed an improvement in cholesterol levels after weight loss.

摘要

背景

大麻素受体 1（CNR1）基因的一个多态性（1359 G/A）被报道为一种常见的多态性（rs1049353），可能对减肥有影响。我们决定研究这种多态性在利拉鲁肽治疗引起的代谢变化和体重减轻中的作用。

方法

我们分析了 86 例 2 型糖尿病和肥胖患者的人群，这些患者单独使用二甲双胍或联合使用磺脲类药物无法控制血糖（糖化血红蛋白 A1c>7%），需要逐渐增加利拉鲁肽剂量至 1.8mg/d 皮下注射。

结果

51 例患者（59.3%）为 G1359G 基因型，35 例患者（40.7%）为 G1359A（28 例，32.6%）或 A1359A（7 例，8.1%）（A 等位基因携带者）。在两种基因型的患者中，基础血糖、HbA1c、体重指数、体重、脂肪量、腰围和收缩压均降低。在 G1359G 基因型的患者中，总胆固醇和低密度脂蛋白胆固醇降低，在 A 等位基因携带者中，胰岛素抵抗的稳态模型评估也降低。