Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the mediterranean diet pattern is low

BACKGROUND: Although the fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet). METHODS: Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed. RESULTS: Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern. CONCLUSIONS: These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition

Seafood Consumption, Omega-3 Fatty Acids Intake, and Life-Time Prevalence of Depression in the PREDIMED-Plus Trial

Background: The aim of this analysis was to ascertain the type of relationship between fish and seafood consumption, omega-3 polyunsaturated fatty acids (ω-3 PUFA) intake, and depression prevalence. Methods: Cross-sectional analyses of the PREDIMED-Plus trial. Fish and seafood consumption and ω-3 PUFA intake were assessed through a validated food-frequency questionnaire. Self-reported life-time medical diagnosis of depression or use of antidepressants was considered as outcome. Depressive symptoms were collected by the Beck Depression Inventory-II. Logistic regression models were used to estimate the association between seafood products and ω-3 PUFA consumption and depression. Multiple linear regression models were fitted to assess the association between fish and long-chain (LC) ω-3 PUFA intake and depressive symptoms. Results: Out of 6587 participants, there were 1367 cases of depression. Total seafood consumption was not associated with depression. The odds ratios (ORs) (95% confidence intervals (CIs)) for the 2nd, 3rd, and 4th quintiles of consumption of fatty fish were 0.77 (0.63–0.94), 0.71 (0.58–0.87), and 0.78 (0.64–0.96), respectively, and p for trend = 0.759. Moderate intake of total LC ω-3 PUFA (approximately 0.5–1 g/day) was significantly associated with a lower prevalence of depression. Conclusion: In our study, moderate fish and LC ω-3 PUFA intake, but not high intake, was associated with lower odds of depression suggesting a U-shaped relationship

Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the mediterranean diet pattern is low

BACKGROUND: Although the fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet). METHODS: Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed. RESULTS: Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern. CONCLUSIONS: These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition

Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption

BACKGROUND: Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood. OBJECTIVE: To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake. METHODS: Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed. RESULTS: FTO rs9939609 was associated with higher body mass index (BMI), waist circumference (WC) and obesity (P<0.05 for all). A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score) were significant and we observed a 7% per-allele increase of being obese (OR=1.07; 95%CI 1.01-1.13). We found relevant statistical interactions (P<0.05) with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P=0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P=0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/-SE: -0.57+/-0.16 g/d per-score-allele; P=0.001). CONCLUSION: Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI

Mediterranean diet and quality of life: baseline cross-sectional analysis of the PREDIMED-PLUS trial

We assessed if a 17-item score capturing adherence to a traditional Mediterranean diet (MedDiet) was associated with better health-related quality of life among older Spanish men and women with overweight or obesity harboring the metabolic syndrome. We analyzed baseline data from 6430 men and women (age 55–70 years) participating in the PREDIMED-Plus study. PREDIMED-Plus is a multi-centre randomized trial testing an energyrestricted MedDiet combined with promotion of physical activity and behavioral therapy for primary cardiovascular prevention compared to a MedDiet alone. Participants answered a 36-item questionnaire about health-related quality of life (HRQoL) and a 17-item questionnaire that assessed adherence to an MedDiet. We used ANCOVA and multivariableadjusted linear regression models to compare baseline adjusted means of the quality of life scales according to categories of adherence to the MedDiet. Higher adherence to the MedDiet was independently associated with significantly better scores in the eight dimensions of HRQoL. Adjusted differences of > = 3 points between the highest and the lowest dietary adherence groups to the MedDiet were observed for vitality, emotional role, and mental health and of > = 2 points for the other dimensions. In conclusion, this study shows a positive association between adherence to a MedDiet and several dimensions of quality of life

Factors associated with successful dietary changes in an energy-reduced Mediterranean diet intervention: a longitudinal analysis in the PREDIMED-plus trial

Purpose Long-term nutrition trials may fail to respond to their original hypotheses if participants do not comply with the intended dietary intervention. We aimed to identify baseline factors associated with successful dietary changes towards an energy-reduced Mediterranean diet (MedDiet) in the PREDIMED-Plus randomized trial. Methods Longitudinal analysis of 2985 participants (Spanish overweight/obese older adults with metabolic syndrome) randomized to the active intervention arm of the PREDIMED-Plus trial. Dietary changes were assessed with a 17-item energyreduced MedDiet questionnaire after 6 and 12 months of follow-up. Successful compliance was defned as dietary changes from baseline of≥5 points for participants with baseline scores<13 points or any increase if baseline score was≥13 points. We conducted crude and adjusted multivariable logistic regression models to identify baseline factors related to compliance. Results Consistent factors independently associated with successful dietary change at both 6 and 12 months were high baseline perceived self-efcacy in modifying diet (OR6-month: 1.51, 95% CI 1.25–1.83; OR12-month: 1.66, 95% CI 1.37–2.01), higher baseline fber intake (OR6-month: 1.62, 95% CI 1.07–2.46; OR12-month: 1.62, 95% CI 1.07–2.45), having>3 chronic conditions (OR6-month: 0.65, 95% CI 0.53–0.79; OR12-month: 0.76, 95% CI 0.62–0.93), and sufering depression (OR6-month: 0.80, 95% CI 0.64–0.99; OR12-month: 0.71, 95% CI 0.57–0.88). Conclusion Our results suggested that recruitment of individuals with high perceived self-efcacy to dietary change, and those who initially follow diets relatively richer in fber may lead to greater changes in nutritional recommendations. Participants with multiple chronic conditions, specifcally depression, should receive specifc tailored interventions

Factors associated with successful dietary changes in an energy-reduced Mediterranean diet intervention: a longitudinal analysis in the PREDIMED-plus trial

Purpose Long-term nutrition trials may fail to respond to their original hypotheses if participants do not comply with the intended dietary intervention. We aimed to identify baseline factors associated with successful dietary changes towards an energy-reduced Mediterranean diet (MedDiet) in the PREDIMED-Plus randomized trial. Methods Longitudinal analysis of 2985 participants (Spanish overweight/obese older adults with metabolic syndrome) randomized to the active intervention arm of the PREDIMED-Plus trial. Dietary changes were assessed with a 17-item energyreduced MedDiet questionnaire after 6 and 12 months of follow-up. Successful compliance was defned as dietary changes from baseline of≥5 points for participants with baseline scores<13 points or any increase if baseline score was≥13 points. We conducted crude and adjusted multivariable logistic regression models to identify baseline factors related to compliance. Results Consistent factors independently associated with successful dietary change at both 6 and 12 months were high baseline perceived self-efcacy in modifying diet (OR6-month: 1.51, 95% CI 1.25–1.83; OR12-month: 1.66, 95% CI 1.37–2.01), higher baseline fber intake (OR6-month: 1.62, 95% CI 1.07–2.46; OR12-month: 1.62, 95% CI 1.07–2.45), having>3 chronic conditions (OR6-month: 0.65, 95% CI 0.53–0.79; OR12-month: 0.76, 95% CI 0.62–0.93), and sufering depression (OR6-month: 0.80, 95% CI 0.64–0.99; OR12-month: 0.71, 95% CI 0.57–0.88). Conclusion Our results suggested that recruitment of individuals with high perceived self-efcacy to dietary change, and those who initially follow diets relatively richer in fber may lead to greater changes in nutritional recommendations. Participants with multiple chronic conditions, specifcally depression, should receive specifc tailored interventions