Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population.

OBJECTIVE: Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet. RESEARCH DESIGN AND METHODS: A randomized trial (two MedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for cardiovascular events. RESULTS: The TCF7L2-rs7903146 polymorphism was associated with type 2 diabetes (odds ratio 1.87 [95% CI 1.62-2.17] for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004). When adherence to the MedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 [95% CI 1.36-6.19]; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjusted HR 0.96 [95% CI 0.49-1.87]; P = 0.892 for TT compared with CC). CONCLUSIONS: Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence.

Consistente asociación del polimorfismo rs7903146 en el gen TCF7L2 con mayor riesgo de diabetes en población mediterránea española / Consistent association of the rs7903146 polymorphism in the TCF7L2 gene with a higher risk of diabetes in a Spanish Mediterranean population

Introducción La diabetes tipo 2 (DT2) puede inducir la expresión de moléculas de adhesión celular (ICAM, VCAM) y citocinas (IL-6 y PCR). Posiblemente asociado con dichos mecanismos, el gen transcription factor 7-like 2 (TCF7L2) ha sido asociado con DT2 en diferentes poblaciones, aunque existen pocos datos en población mediterránea. Nuestro objetivo es estudiar la asociación de dicho gen con la DT2 y marcadores de inflamación en población de alto riesgo cardiovascular. Métodos Se incluyeron 1.001 participantes de alto riesgo cardiovascular del estudio PREDIMED-Valencia. Se determinó la glucemia en ayunas y las concentraciones de lípidos plasmáticos. En una submuestra aleatoria se determinaron las concentraciones de IL-6, PCR, VCAM e ICAM. Se analizó el polimorfismo rs7903146 (C>T) en el gen TCF7L2. Resultados La prevalencia de DT2 fue de 47,4%. La frecuencia de genotipos fue: 38,1% CC, 47,7% CT y 14,3% TT, siendo la frecuencia alélica del alelo T 0,381. Se hallaron diferencias significativas de concentraciones plasmáticas de glucosa según el genotipo (CC: 117,3±37,8; CT: 124,1±41,1; TT: 128,7±45,2mg/dl; p=0,011). Los portadores del alelo T presentan un mayor riesgo de DT2 (OR=1,37; 95%IC: 1,05-1,80; p=0,022) con respecto a individuos CC. El alelo T también se asoció como mayores concentraciones de VCAM (CC: 914,3±355,4; CT: 1.147,0±422,6; TT: 1.258,1±447,3 ng/ml; p=0,001). No se encontraron diferencias estadísticamente significativas para los demás marcadores de inflamación. Conclusión El alelo T del polimorfismo rs7903146 en el gen TCF7L2 se asocia con un mayor riesgo de DT2 en población mediterránea española, siendo consistente con los resultados obtenidos en otras poblaciones europeas (AU)

Introduction: Type 2 diabetes (T2D) can induce the expression of cell adhesion molecules (ICAM,VCAM) and cytokines (IL-6 and CRP). Possibly related to these mechanisms, the transcription factor 7-like 2 (TCF7L2) gene has been associated with T2D in distinct populations, but there are few data for the Mediterranean population. Our objective was to study the association of this gene with T2D and inflammation markers in a population at high cardiovascular risk. Methods: We included 1,001 high cardiovascular risk participants in the PREDIMED-Valencia study. Fasting blood glucose and plasma lipid concentrations were determined. Plasma concentrations of IL-6, CRP, VCAM and ICAM were also determined in a random subsample. Thers7903146 (C > T) polymorphism in the TCF7L2 gene was analyzed. Results: The prevalence of T2D was 47.4%. The frequency of genotypes was 38.1% for CC,47.7% for CT and 14.3% for TT (the allelic frequency of the T allele was 0.381). We found statistically significant differences in fasting plasma glucose concentrations depending on theTCF7L2 genotype (CC: 117.3±37.8; CT: 124.1±41.1; TT: 128.7±45.2 mg/dl; p = 0.011). Tallele carriers had an increased risk of T2D (OR = 1.37; 95% CI: 1.05-1.80; p = 0.022) compared with CC individuals. The T allele was also associated with higher concentrations of VCAM(CC: 914.3±355.4; CT: 1147.0±422.6; TT: 1258.1±447.3 ng/ml; p = 0.001). No statistically significant differences were found for the other markers of inflammation. Conclusion: Consistent with the results obtained in other European populations, this study found that the T allele of the rs7903146 polymorphism in the TCF7L2 gene is associated with an increased risk of T2D in a Mediterranean Spanish population (AU)

Exercise, genetics and prevention of type 2 diabetes.

Type 2 diabetes is one of the fastest growing public health problems in both developed and developing countries. Cardiovascular disease is the most prevalent complication of type 2 diabetes. In the past decade, the associations of physical activity, physical fitness and changes in the lifestyle with the risk of type 2 diabetes have been assessed by a number of prospective studies and clinical trials. A few studies have also evaluated the joint associations of physical activity, body mass index and glucose levels with the risk of type~2 diabetes. The results based on prospective studies and clinical trials have shown that moderate or high levels of physical activity or physical fitness and changes in the lifestyle (dietary modification and increase in physical activity) can prevent type 2 diabetes.

Familial resemblance for muscle phenotypes in the HERITAGE Family Study.

INTRODUCTION/PURPOSE: We hypothesized that skeletal muscle histological and biochemical phenotypes aggregate within families. METHODS: Nineteen families (78 Caucasians) from the HERITAGE Family Study participated in the study. Proportions and areas of Type I, IIA, and IIX muscle fibers, capillary density, and maximal enzyme activities were determined in biopsy samples from the vastus lateralis obtained in the sedentary state and after a 20-wk endurance-training program. RESULTS: In the sedentary state, there was evidence for familial resemblance for Type I fiber area (P = 0.007), number of capillaries around Type I and Type IIA fibers (P = 0.04), and Type I and IIA fiber areas per capillary (P = 0.01 and P = 0.04, respectively). Significant familial aggregation (0.05>P > 0.0001) was observed for maximal activities of enzymes of the energy production pathways. With regard to the training response, significant familial aggregation (0.05 > P < 0.0001) was observed for maximal activities of enzymes of the energy production pathways. CONCLUSION: These data provide evidence of familial aggregation for enzyme activities of the main energy metabolism pathways of the skeletal muscle in the sedentary state and in response to regular exercise.