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

• Published in: Diabetes care Vol. 36; no. 11; pp. 3803 - 3811
• Main Authors: CORELLA, Dolores, CARRASCO, Paula, LAPETRA, José, SERRA-MAJEM, Lluís, RUIZ-GUTIERREZ, Valentina, WARNBERG, Julia, FIOL, Miquel, PINTO, Xavier, ORTEGA-AZORIN, Carolina, ANGEL MUNOZ, Miguel, ALFREDO MARTINEZ, J, GOMEZ-GRACIA, Enrique, SORLI, Jose V, GONZALEZ, José I, ROS, Emilio, OROOVAS, José M, ESTRUCH, Ramón, RICO-SANZ, Jesús, ANGEL MARTINEZ-GONZALEZ, Miguel, SALAS-SALVADO, Jordi, ISABEL COVAS, M, COLTELL, Oscar, AROS, Fernando
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.11.2013
• Subjects: Aged; Biological and medical sciences; Blood lipids; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - prevention & control; Cholesterol; Dextrose; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Diet, Mediterranean; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Fasting - blood; Female; Genetic aspects; Glucose; Humans; Incidence; Lipids; Male; Medical sciences; Metabolic diseases; Middle Aged; Neurology; Odds Ratio; Original Research; Plasma; Polymorphism; Polymorphism, Genetic; Regression analysis; Risk Factors; Stroke (Disease); Stroke - embryology; Stroke - prevention & control; Transcription Factor 7-Like 2 Protein - genetics; Triglycerides - blood; Type 2 diabetes; Vascular diseases and vascular malformations of the nervous system; Spain; Human; High risk; Nervous system diseases; Stroke; Nutrition; Mediterranean diet; Metabolic diseases; Cardiovascular disease; Randomized controlled trial; Cerebral disorder; Incidence; Vascular disease; Randomization; Central nervous system disease; Risk factor; Cardiovascular risk; Secondary effect; Clinical trial; Population; Cerebrovascular disease; Endocrinology; Polymorphism
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc13-0955

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. 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. 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). Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence.