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

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

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.

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Variation / genetics*
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide 1 / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin Resistance / genetics
  • Liraglutide
  • Male
  • Middle Aged
  • Obesity / drug therapy
  • Obesity / epidemiology
  • Obesity / genetics*
  • Prospective Studies
  • Receptor, Cannabinoid, CB1 / genetics*
  • Risk Factors
  • Treatment Outcome
  • Weight Loss / genetics*

Substances

  • CNR1 protein, human
  • Hypoglycemic Agents
  • Receptor, Cannabinoid, CB1
  • Liraglutide
  • Glucagon-Like Peptide 1