Effects of a high-protein/low-carbohydrate versus a standard hypocaloric diet on adipocytokine levels and cardiovascular risk factors during 9 months, role of rs6923761 gene variant of glucagon-like peptide 1 receptor.

BACKGROUND: The role of GLP-1 R variants on body weight response after dietary intervention is unclear. OBJECTIVE: The aim was to investigate the role of this polymorphism on cardiovascular risk factors, adipokine levels and weight loss secondary to a high-protein/low-carbohydrate vs. standard hypocaloric diets during 9 months. DESIGN: 211 obese subjects were randomly allocated to one of these two diets for a period of 9 months; diet HP (high protein/low carbohydrate) and diet S (standard). RESULTS: Ninety-four patients (44.5%) had the genotype GG (wild group) and 117 (55.5%) patients had the next genotypes; GA (89 patients, 42.2%) or AA (28 patients, 13.3%) (mutant group). With both diets and in both genotype groups, body mass index, weight, fat mass, waist circumference and systolic blood pressure decreased. Anthropometric parameters were higher in non-A allele carriers than A allele carriers. With diet HP in both genotypes, LDL cholesterol, total cholesterol, leptin, insulin levels and HOMA-R decreased. With the diet S and only in wild genotype, the same parameters decreased, too. CONCLUSION: Our data showed a lack of association of rs6923761 GLP-1 R polymorphism with weight loss. Better anthropometric parameters in obese subjects with the mutant allele (A) of rs6923761 GLP-1 R polymorphism were observed. Total cholesterol, LDL cholesterol, insulin levels and HOMA-R decreased in all patients with both diets, although A allele carriers treated with standard diet did not show these changes.

Role of rs6923761 gene variant in glucagon-like peptide 1 receptor in basal GLP-1 levels, cardiovascular risk factor and serum adipokine levels in naïve type 2 diabetic patients.

BACKGROUND: Role of GLP-1 variants on basal GLP-1 levels, body weight and cardiovascular risk factors remains unclear in patients with diabetes mellitus type 2. OBJECTIVE: Our aim was to analyze the effects of rs6923761 GLP-1 receptor polymorphism on body weight, cardiovascular risk factors, basal GLP-1 levels and serum adipokine levels in naïve patients with diabetes mellitus type 2. DESIGN: A sample of 104 naïve patients with diabetes mellitus type 2 was enrolled in a prospective way. Basal fasting glucose, c-reactive protein (CRP), insulin, insulin resistance (HOMA), total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides concentration, basal GLP-1, HbA1c and adipokines (leptin, adiponectin, resistin) levels were determined. Weights, body mass index, waist circumference, fat mass by bioimpedance and blood pressure measures were measured. RESULTS: Forty-nine patients (47.1%) had the genotype GG and 55 (52.9%) diabetic subjects had the next genotypes; GA (44 patients, 42.3%) or AA (11 study subjects, 10.6%) (second group). In A allele carriers, basal GLP-1 levels were higher than non-carriers (2.9 ± 2.1 ng/ml; p < 0.05). No differences were detected between both genotype groups. CONCLUSION: Our cross-sectional study revealed an association between the rs6923761 GLP-1 receptor polymorphism (A allele carriers) and basal GLP-1 levels in naïve patients with diabetes mellitus type 2.

Relation of the rs6923761 gene variant in glucagon-like peptide 1 receptor with weight, cardiovascular risk factor, and serum adipokine levels in obese female subjects.

BACKGROUND: Studies of the glucagon-like peptide 1 (GLP-1) receptor have been directed at identifying polymorphisms in the GLP-1 receptor gene that may be a contributing factor in the pathogenesis of diabetes mellitus and cardiovascular risk factors. Nevertheless, the role of GLP-1 variants on body weight, cardiovascular risk factors, and adipokines remains unclear in obese patients. OBJECTIVE: Our aim was to analyze the effects of rs6923761 GLP-1 receptor polymorphism on body weight, cardiovascular risk factors, and serum adipokine levels in nondiabetic obese females. DESIGN: A sample of 645 obese nondiabetic Caucasian females was enrolled in a prospective way. Basal fasting glucose, c-reactive protein (CRP), insulin, insulin resistance (homeostasis model assessment (HOMA)), total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides concentration, and adipokines were measured. Weights, body mass index (BMI), waist circumference, fat mass by bioimpedance, and blood pressure measures were measured. RESULTS: Three hundred and twenty-seven participants (50.7%) had the genotype GG and 318 (49.3%) study subjects had the next genotypes; GA (270 study subjects, 41.9%) or AA (48 study subjects, 7.4%) (second group). In wild group (GG genotype), BMI (1.8 ± 2.3 kg/m(2) ; P < 0.05), weight (3.1 ± 1.3 kg; P < 0.05), fat mass (2.4 ± 1.1 kg; P < 0.05), waist circumference (2.7 ± 1.9 cm; P < 0.05), triglyceride levels (10.4 ± 5.3 mg/dl; P < 0.05), interleukin 6 (IL-6) (1.5 ± 0.9 ng/dl; P < 0.05), resistin (1.1 ± 0.3 ng/dl; P < 0.05), and leptin (30.1 ± 10.3 ng/dl; P < 0.05) levels were higher than mutant group (GA + AA). CONCLUSION: Data from our study revealed an association with decreased metabolic and cardiovascular markers in obese females. BMI weight, fat mass, waist circumference, triglycerides, leptin, resistin, and IL-6 serum levels were lower in subjects with A allele than non-A allele subjects.

rs6923761 gene variant in glucagon-like peptide 1 receptor: Allelic frequencies and influence on cardiovascular risk factors in a multicenter study of Castilla-Leon.

BACKGROUND: Some GLP-1 receptor studies have identified polymorphisms in the GLP-1 receptor gene that might be related to different cardiovascular risk factors. OBJECTIVE: Our aim was to investigate the allelic distribution of rs6923761 GLP-1 receptor polymorphism in a geographic area of Spain (Community of Castilla y Leon) and to evaluate the influence of this polymorphism on obesity anthropometric parameters and cardiovascular risk factors in the fasted state in obese patients. DESIGN: A sample of 341 obese subjects (body mass index ≥ 30 kg/m2) was analyzed. Fasting blood glucose, C-reactive protein (CRP), plasma insulin, insulin resistance (HOMA-IR), and lipid profile were determined. Anthropometric parameters, dietary intake and blood pressure were recorded. RESULTS: One hundred and forty three patients (42.0%) had the genotype GG (wild-type group) and one hundred and ninety eight (58.0%) patients were A carriers: GA (164 patients, 48.1%) or AA (34 patients, 9.9%) (mutant-type group). Valladolid and Segovia health areas had the lowest percentage of wild type genotype and G allelic (than other Health Areas). Burgos Health Area had a higher percentage of wild-type genotype. In wild-type group (GG genotype), BMI (0.9 ± 1.3 kg/m2; p < 0.05), weight (3.3 ± 1.1 kg; p < 0.05), fat mass (2.5 ± 1.1 kg; p < 0.05), waist to hip ratio (0.02 ± 0.005 cm; p < 0.05), waist circumference (2.8 ± 1.1 cm; p < 0.05), triglycerides (14.4 ± 3.3 mg/dl; p < 0.05) insulin (3.1 ± 1.0 mg/dl; p < 0.05) and HOMA-IR (1.2 ± 0.9 mg/dl; p < 0.05) were higher than A allele carriers. In non A allele carriers, lower HDL cholesterol levels than A allele carriers (6.4 ± 2.3 mg/dl; p < 0.05) were found. CONCLUSION: Data from our study revealed different allelic distribution in this geographic area, with better parameters (Body mass index, weight, fat mass, waist circumference, triglycerides, insulin, HOMA-IR and HDL cholesterol) in A allele carriers than in non A allele carriers.

Allelic variant in the glucagon-like peptide 1 receptor gene associated with greater effect of liraglutide and exenatide on gastric emptying: A pilot pharmacogenetics study.

BACKGROUND: Weight loss in response to the long-acting GLP-1 receptor (GLP1R) analog, liraglutide, is correlated with delay in gastric-emptying (GE). The aim of this pilot study was to assess whether specific genetic variants in GLP1R or TCF7L2 are associated with delayed GE and weight loss in obese patients treated with liraglutide or the short-acting GLP-1 agonist, exenatide. METHODS: We evaluated in obese individuals the associations of genetic variations of GLP1R (rs6923761) and TCF7L2 (rs7903146) on GE T1/2 and weight from two trials that evaluated separately exenatide, 5 µg BID for 30 days, or liraglutide, 3 mg daily for 5 weeks. Data were analyzed using the dominant genetic model and intention-to-treat analysis. KEY RESULTS: There was a significant correlation between changes in weight and GE T1/2 (rs  = -.382, P = .004). GLP1R rs6923761 minor allele A (AA_AG) carriers who received either exenatide or liraglutide had greater delay in GE T1/2 relative to baseline (117.9 ± 27.5 [SEM] minutes and 128.9 ± 38.32 minutes) compared to GG genotype (95.8 ± 30.4 minutes and 61.4 ± 21.4 minutes, respectively; P = .11). There was a non-significant difference in weight loss based on GLP1R rs6923761 genotype after 5 weeks of treatment. There were no significant correlations with TCF7L2 (rs7903146) genotype. CONCLUSIONS & INFERENCES: The minor A allele of GLP1R (rs6923761) is associated with greater delay in GE T1/2 in response to liraglutide and exenatide. These studies provide data to plan pharmacogenetics testing of the hypothesis that GLP1R (rs6923761) influences weight loss in response to GLP1R agonists.

Evaluation of weight loss and metabolic changes in diabetic patients treated with liraglutide, effect of RS 6923761 gene variant of glucagon-like peptide 1 receptor.

BACKGROUND: A polymorphism of GLP-1 R (rs6923761) has potential implications in weight loss and metabolic control. We decide to investigate the role of this polymorphism on metabolic changes and weight loss secondary to treatment with liraglutide. MATERIAL AND METHODS: A population of 90 patients with diabetes mellitus type 2 and overweight, unable to achieve glycemic control (HbA1c>7%) with metformin alone that require initiation of liraglutide treatment in progressive dose to 1.8mg/day subcutaneously, was analyzed. RESULTS: Fifty one patients (56.7%) had the genotype GG and 39 (43.3%) patients; GA (30 patients, 33.3%) or AA (9 patients, 10%) (A allele carriers). In patients with both genotypes, body mass index (BMI), weight and fat decreased. The proportion of the mentioned reductions was higher in the variant allele carriers; BMI (-0.59±2.5kg/m(2) vs. -1.69±3.9kg/m(2); P<0.05), weight (-2.78±2.8kg vs. -4.52±4.6kg; P<0.05) and fat mass (-0.59±2.5kg vs. -1.69±3.9kg; P<0.05). Weight reduction after liraglutide treatment was greater in the A-allele carriers by 2.9kg (95% CI: 0.27-5.64). The decrease of basal glucose, HOMA-R and HbA1c was similar in both genotypes. CONCLUSION: Our data showed better anthropometric parameters in overweight diabetic subjects with the variant allele (A) of rs6923761 GLP-1 R polymorphism. A allele carriers had a greater decrease in weight and fat mass after treatment with liraglutide. The present study is a preliminary observation, and its results need to be replicated with a higher number of patients in different populations.