Dora Romaguera

Prevention of Diabetes With Mediterranean Diets: A Subgroup Analysis of a Randomized Trial

Context Can changes in diet prevent diabetes in older adults? Contribution This subgroup analysis of a multicenter trial involved older adults with high risk for heart disease who were randomly assigned to a Mediterranean diet supplemented with either extra-virgin olive oil or mixed nuts or to a low-fat control diet. Neither energy restriction nor increased physical activity was advised. After 4 years of follow-up, fewer persons in the Mediterranean diet groups developed diabetes than in the control group. Implication Changes in dietary patterns that do not necessarily lead to weight loss or include energy restrictions could help prevent diabetes in some older adults. The Editors Type 2 diabetes mellitus represents a major health problem because worldwide prevalence has more than doubled in the past 3 decades, with nearly 347 million persons with diabetes in 2010 (1), and is a potent risk factor for cardiovascular disease (CVD), blindness, renal failure, and lower limb amputation (2). Compelling evidence shows that diabetes can be prevented with lifestyle changes. Intensive lifestyle modification promoting weight loss through energy-restricted diets together with increased physical activity can decrease incident diabetes to as low as 50% (3). Indeed, lifestyle modification has performed better than pharmacologic approaches (such as metformin or rosiglitazone) in diabetes prevention (46). Of interest, the benefit of lifestyle changes in decreasing diabetes risk seems to extend beyond the termination of active intervention (68). However, there is little information on whether changes in the overall dietary pattern, without energy restriction, increased physical activity, and ensuing weight loss, may also be effective to prevent diabetes. Prospective epidemiologic studies strongly suggest that dietary patterns characterized by high consumption of fruit, vegetables, whole grains, and fish and reduced consumption of red and processed meat, sugar-sweetened beverages, and starchy foods delay diabetes onset (9). In the last 6 years, the traditional Mediterranean diet has emerged as a healthy dietary pattern that is also associated with a decreased risk for diabetes (1012). The Mediterranean diet is moderately rich in fat (35% to 40% of energy), especially from vegetable sources (rich in olive oil and nuts), and relatively low in dairy products. Moderate consumption of alcohol, mostly wine, and frequent use of sauces with tomato, onions, garlic, and spices for meal preparation are also typical. Preliminary data from the PREDIMED (Prevencin con Dieta Mediterrnea) study (1317) showed that traditional Mediterranean diets enriched with high-fat foods of vegetable origin decreased the incidence of diabetes (18). However, that report studied participants only from 1 of the 11 PREDIMED recruiting centers. In this analysis, we provide the final results on diabetes incidence in the whole multicenter trial after a median follow-up of 4.1 years. Methods Design Overview The PREDIMED study is a parallel-group, randomized, primary cardiovascular prevention trial done in Spain in persons at high risk but without CVD at baseline. The protocol, design, objectives, and methods have been reported in detail elsewhere (13, 14). Briefly, participants were randomly assigned in a 1:1:1 ratio to 1 of 3 nutrition interventions: Mediterranean diet supplemented with extra-virgin olive oil (EVOO), Mediterranean diet supplemented with mixed nuts, or a control diet consisting of advice to reduce intake of all types of fat. A complete list of PREDIMED study investigators is available in Supplement 1. The local institutional review boards approved the protocol at each study location, and all participants provided written informed consent. Supplement. Original Version (PDF) Supplement 1. List of Prevencin con Dieta Mediterrnea Study Investigators Setting and Participants Eligible participants were community-dwelling men (aged 55 to 80 years) and women (aged 60 to 80 years) without CVD at baseline who had either type 2 diabetes or at least 3 or more cardiovascular risk factors, namely current smoking, hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol levels, overweight or obesity, and family history of premature CVD. Exclusion criteria have previously been reported (13). Randomization and Intervention From October 2003 to June 2009, 7447 suitable candidates were enrolled in the trial. The study nurse from each recruiting center randomly assigned each participant to the corresponding intervention group following computer-generated random numbers for allocation contained in sealed envelopes, which were centrally prepared for each center by the coordinating unit. Four strata of randomization were built by sex and age (cutoff, 70 years) but not by baseline diabetes status. The primary care physicians did not participate in the randomization process. The study nurses were independent of the nursing staff of the primary care health centers. Therefore, they were not involved in the usual clinical care of participants, and their exclusive role was to collect data for the trial. Given the nature of the interventions (nutritional advice and provision of foods), only investigators assessing outcomes were blinded with respect to intervention assignment. This was done by providing them with coded data sets and medical records blinded with respect to the personal identity of the participant and without any information on treatment allocation. Because our main objective was to determine the effect of the 3 interventions on diabetes incidence, this report includes data only on participants who did not have diabetes at baseline and for whom we could ascertain the incidence of diabetes during follow-up (n= 3541) (Figure 1). Figure 1. Study flow diagram. EVOO = extra-virgin olive oil; MedDiet = Mediterranean diet. A behavioral intervention promoting the Mediterranean diet was implemented in the corresponding groups of the trial, as described (13). Dietitians gave personalized advice to participants about the amount and use of EVOO for cooking and dressing; weekly intake of nuts; increased consumption of vegetables, fruits, legumes, and fish; recommended intake of white meat instead of red or processed meat; avoidance of butter, fast food, sweets, pastries, or sugar-sweetened beverages; and the dressing of dishes with sofrito sauce (using tomato, garlic, onion, and spices simmered in olive oil). Reduction of alcoholic beverages other than wine was advised to all participants. Wine with meals was recommended with moderation only to habitual drinkers. At baseline and quarterly thereafter, dietitians conducted individual and group dietary training sessions to provide information on typical Mediterranean foods, seasonal shopping lists, meal plans, and recipes for each group. In each session, a 14-item questionnaire was used to assess adherence to the Mediterranean diet (13, 14) so that personalized advice could be provided to upgrade participants adherence. The same questionnaire was assessed yearly in the control group. Participants assigned to the 2 Mediterranean diet groups received allotments of either EVOO (50 mL/d) or mixed nuts (30 g/d: 15 g of walnuts, 7.5 g of almonds, and 7.5 g of hazelnuts) at no cost. Participants assigned to the control diet received recommendations to reduce intake of all types of fat (from both animal and vegetable sources) and received nonfood gifts (kitchenware, tableware, aprons, or shopping bags). Through October 2006, participants in the control group received only a leaflet describing the low-fat diet. Thereafter, participants assigned to the control diet also received personalized advice and were invited to group sessions with the same frequency and intensity as those in the Mediterranean diet groups. A separate 9-item dietary questionnaire (14) was used to assess adherence to the low-fat diet. Neither energy restriction nor increased physical activity was advised for any intervention group. At baseline examination and yearly during follow-up, we administered a 137-item validated semiquantitative food-frequency questionnaire (19); the validated Spanish version of the Minnesota Leisure-time Physical Activity Questionnaire (20); and a 47-item questionnaire about education, lifestyle, medical history, and medication use. At baseline, trained personnel performed electrocardiography and anthropometric and blood pressure measurements. Blood pressure was measured in triplicate by using a validated semiautomatic oscillometer with a 5-minute interval between measurements and the participant in a sitting position (Omron HEM-705CP, Omron, Hoofddorp, the Netherlands). Fasting blood and spot urine were sampled at baseline and follow-up years 1, 3, 5, and 7. After an overnight fast, tubes for EDTA plasma, citrate plasma, and serum and urine samples were collected and aliquots were coded and stored at 80C in the central laboratory until analysis. Serum glucose, cholesterol, and triglyceride levels were measured using standard enzymatic methods. High-density lipoprotein cholesterol was measured after precipitation with phosphotungstic acid and magnesium chloride. Biomarkers of adherence to the supplemental foods, including urine hydroxytyrosol levels and plasma -linolenic acid proportions, which are reliable biomarkers of EVOO and walnut intake, respectively, were measured in random subsamples of participants during the first 5 years of follow-up (by gas chromatographymass spectrometry and by gas chromatography, respectively). Laboratory technicians were blinded to intervention group. Outcomes and Follow-up Diabetes was a prespecified secondary outcome of the PREDIMED trial. IT was considered to be present at baseline by clinical diagnosis or use of antidiabetic medication. New-onset diabetes during follow-up was diagnosed using the American Diabetes Association criteria, namely fasting plasma glucose levels of 7.0 mmol/L or g

Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study

Objective To compute the burden of cancer attributable to current and former alcohol consumption in eight European countries based on direct relative risk estimates from a cohort study. Design Combination of prospective cohort study with representative population based data on alcohol exposure. Setting Eight countries (France, Italy, Spain, United Kingdom, the Netherlands, Greece, Germany, Denmark) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Participants 109 118 men and 254 870 women, mainly aged 37-70. Main outcome measures Hazard rate ratios expressing the relative risk of cancer incidence for former and current alcohol consumption among EPIC participants. Hazard rate ratios combined with representative information on alcohol consumption to calculate alcohol attributable fractions of causally related cancers by country and sex. Partial alcohol attributable fractions for consumption higher than the recommended upper limit (two drinks a day for men with about 24 g alcohol, one for women with about 12 g alcohol) and the estimated total annual number of cases of alcohol attributable cancer. Results If we assume causality, among men and women, 10% (95% confidence interval 7 to 13%) and 3% (1 to 5%) of the incidence of total cancer was attributable to former and current alcohol consumption in the selected European countries. For selected cancers the figures were 44% (31 to 56%) and 25% (5 to 46%) for upper aerodigestive tract, 33% (11 to 54%) and 18% (−3 to 38%) for liver, 17% (10 to 25%) and 4% (−1 to 10%) for colorectal cancer for men and women, respectively, and 5.0% (2 to 8%) for female breast cancer. A substantial part of the alcohol attributable fraction in 2008 was associated with alcohol consumption higher than the recommended upper limit: 33 037 of 178 578 alcohol related cancer cases in men and 17 470 of 397 043 alcohol related cases in women. Conclusions In western Europe, an important proportion of cases of cancer can be attributable to alcohol consumption, especially consumption higher than the recommended upper limits. These data support current political efforts to reduce or to abstain from alcohol consumption to reduce the incidence of cancer.

Is concordance with World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention related to subsequent risk of cancer? Results from the EPIC study

BACKGROUND In 2007 the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) issued 8 recommendations (plus 2 special recommendations) on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE We aimed to investigate whether concordance with the WCRF/AICR recommendations was related to cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. DESIGN The present study included 386,355 EPIC participants from 9 European countries. At recruitment, dietary, anthropometric, and lifestyle information was collected. A score was constructed based on the WCRF/AICR recommendations on weight management, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, alcoholic drinks, and breastfeeding for women; the score range was 0-6 for men and 0-7 for women. Higher scores indicated greater concordance with WCRF/AICR recommendations. The association between the score and cancer risk was estimated by using multivariable Cox regression models. RESULTS Concordance with the score was significantly associated with decreased risk of cancer. A 1-point increment in the score was associated with a risk reduction of 5% (95% CI: 3%, 7%) for total cancer, 12% (95% CI: 9%, 16%) for colorectal cancer, and 16% (95% CI: 9%, 22%) for stomach cancer. Significant associations were also observed for cancers of the breast, endometrium, lung, kidney, upper aerodigestive tract, liver, and esophagus but not for prostate, ovarian, pancreatic, and bladder cancers. CONCLUSION Adherence to the WCRF/AICR recommendations for cancer prevention may lower the risk of developing most types of cancer.

Mediterranean dietary pattern and cancer risk in the EPIC cohort

Background:Although several studies have investigated the association of the Mediterranean diet with overall mortality or risk of specific cancers, data on overall cancer risk are sparse.Methods:We examined the association between adherence to Mediterranean dietary pattern and overall cancer risk using data from the European Prospective Investigation Into Cancer and nutrition, a multi-centre prospective cohort study including 142 605 men and 335 873. Adherence to Mediterranean diet was examined using a score (range: 0–9) considering the combined intake of fruits and nuts, vegetables, legumes, cereals, lipids, fish, dairy products, meat products, and alcohol. Association with cancer incidence was assessed through Cox regression modelling, controlling for potential confounders.Results:In all, 9669 incident cancers in men and 21 062 in women were identified. A lower overall cancer risk was found among individuals with greater adherence to Mediterranean diet (hazard ratio=0.96, 95% CI 0.95–0.98) for a two-point increment of the Mediterranean diet score. The apparent inverse association was stronger for smoking-related cancers than for cancers not known to be related to tobacco (P (heterogeneity)=0.008). In all, 4.7% of cancers among men and 2.4% in women would be avoided in this population if study subjects had a greater adherence to Mediterranean dietary pattern.Conclusion:Greater adherence to a Mediterranean dietary pattern could reduce overall cancer risk.

Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study

BACKGROUND The Mediterranean dietary pattern is believed to protect against cancer, although evidence from cohort studies that have examined particular cancer sites is limited. OBJECTIVE We aimed to explore the association between adherence to a relative Mediterranean diet (rMED) and incident gastric adenocarcinoma (GC) within the European Prospective Investigation into Cancer and Nutrition study. DESIGN The study included 485,044 subjects (144,577 men) aged 35-70 y from 10 European countries. At recruitment, dietary and lifestyle information was collected. An 18-unit rMED score, incorporating 9 key components of the Mediterranean diet, was used to estimate rMED adherence. The association between rMED and GC with respect to anatomic location (cardia and noncardia) and histologic types (diffuse and intestinal) was investigated. A calibration study in a subsample was used to control for dietary measurement error. RESULTS After a mean follow-up of 8.9 y, 449 validated incident GC cases were identified and used in the analysis. After stratification by center and age and adjustment for recognized cancer risk factors, high compared with low rMED adherence was associated with a significant reduction in GC risk (hazard ratio: 0.67; 95% CI: 0.47, 0.94). A 1-unit increase in the rMED score was associated with a decreased risk of GC of 5% (95% CI: 0.91, 0.99). There was no evidence of heterogeneity between different anatomic locations or histologic types. The calibrated results showed similar trends (overall hazard ratio for GC: 0.93; 95% CI: 0.89, 0.99). CONCLUSION Greater adherence to an rMED is associated with a significant reduction in the risk of incident GC.

Adherence to the Mediterranean Diet Is Associated with Lower Abdominal Adiposity in European Men and Women

Given the lack of consistent evidence of the relationship between Mediterranean dietary patterns and body fat, we assessed the cross-sectional association between adherence to a modified Mediterranean diet, BMI, and waist circumference (WC). A total of 497,308 individuals (70.7% women) aged 25-70 y from 10 European countries participated in this study. Diet was assessed at baseline using detailed validated country-specific questionnaires, and anthropometrical measurements were collected using standardized procedures. The association between the degree of adherence to the modified-Mediterranean Diet Score (mMDS) (including high consumption of vegetables, legumes, fruits and nuts, cereals, fish and seafood, and unsaturated:saturated fatty acids ratio; moderate alcohol intake; and low consumption of meat and meat products and dairy products) and BMI (kg.m(-2)) or WC (cm) was modeled through mixed-effects linear regression, controlling for potential confounders. Overall, the mMDS was not significantly associated with BMI. Higher adherence to the Mediterranean diet was significantly associated with lower WC, for a given BMI, in both men (-0.09; 95% CI -0.14 to -0.04) and women (-0.06; 95% CI -0.10 to -0.01). The association was stronger in men (-0.20; 95% CI -0.23 to -0.17) and women (-0.17; 95% CI -0.21 to -0.13) from Northern European countries. Despite the observed heterogeneity among regions, results of this study suggest that adherence to a modified Mediterranean diet, high in foods of vegetable origin and unsaturated fatty acids, is associated with lower abdominal adiposity measured by WC in European men and women.

Mediterranean dietary patterns and prospective weight change in participants of the EPIC-PANACEA project

BACKGROUND There is an association between a greater adherence to a Mediterranean diet and a reduced risk of developing chronic diseases. However, it is not clear whether this dietary pattern may be protective also against the development of obesity. OBJECTIVE We assessed the association between the adherence to the Mediterranean dietary pattern (MDP), prospective weight change, and the incidence of overweight or obesity. DESIGN We conducted a prospective cohort study [the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol Consumption, Cessation of Smoking, Eating Out of Home, and Obesity (EPIC-PANACEA) project] in 373,803 individuals (103,455 men and 270,348 women; age range: 25-70 y) from 10 European countries. Anthropometric measurements were obtained at recruitment and after a median follow-up time of 5 y. The relative Mediterranean Diet Score (rMED; score range: 0-18) was used to assess adherence to the MDP according to the consumption of 9 dietary components that are characteristic of the Mediterranean diet. The association between the rMED and 5-y weight change was modeled through multiadjusted mixed-effects linear regression. RESULTS Individuals with a high adherence to the MDP according to the rMED (11-18 points) showed a 5-y weight change of -0.16 kg (95% CI: -0.24, -0.07 kg) and were 10% (95% CI: 4%, 18%) less likely to develop overweight or obesity than were individuals with a low adherence to the MDP (0-6 points). The low meat content of the Mediterranean diet seemed to account for most of its positive effect against weight gain. CONCLUSION This study shows that promoting the MDP as a model of healthy eating may help to prevent weight gain and the development of obesity.

Mediterranean diet and type 2 diabetes risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study: the InterAct project.

OBJECTIVE To study the association between adherence to the Mediterranean dietary pattern (MDP) and risk of developing type 2 diabetes, across European countries. RESEARCH DESIGN AND METHODS We established a case-cohort study including 11,994 incident type 2 diabetic case subjects and a stratified subcohort of 15,798 participants selected from a total cohort of 340,234 participants with 3.99 million person-years of follow-up, from eight European cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The relative Mediterranean diet score (rMED) (score range 0–18) was used to assess adherence to MDP on the basis of reported consumption of nine dietary components characteristic of the Mediterranean diet. Cox proportional hazards regression, modified for the case-cohort design, was used to estimate the association between rMED and risk of type 2 diabetes, adjusting for confounders. RESULTS The multiple adjusted hazard ratios of type 2 diabetes among individuals with medium (rMED 7–10 points) and high adherence to MDP (rMED 11–18 points) were 0.93 (95% CI 0.86–1.01) and 0.88 (0.79–0.97), respectively, compared with individuals with low adherence to MDP (0–6 points) (P for trend 0.013). The association between rMED and type 2 diabetes was attenuated in people <50 years of age, in obese participants, and when the alcohol, meat, and olive oil components were excluded from the score. CONCLUSIONS In this large prospective study, adherence to the MDP, as defined by rMED, was associated with a small reduction in the risk of developing type 2 diabetes in this European population.

Meat consumption and prospective weight change in participants of the EPIC-PANACEA study

BACKGROUND Meat intake may be related to weight gain because of its high energy and fat content. Some observational studies have shown that meat consumption is positively associated with weight gain, but intervention studies have shown mixed results. OBJECTIVE Our objective was to assess the association between consumption of total meat, red meat, poultry, and processed meat and weight gain after 5 y of follow-up, on average, in the large European population who participated in the European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (EPIC-PANACEA) project. DESIGN A total of 103,455 men and 270,348 women aged 25-70 y were recruited between 1992 and 2000 in 10 European countries. Diet was assessed at baseline with the use of country-specific validated questionnaires. A dietary calibration study was conducted in a representative subsample of the cohort. Weight and height were measured at baseline and self-reported at follow-up in most centers. Associations between energy from meat (kcal/d) and annual weight change (g/y) were assessed with the use of linear mixed models, controlled for age, sex, total energy intake, physical activity, dietary patterns, and other potential confounders. RESULTS Total meat consumption was positively associated with weight gain in men and women, in normal-weight and overweight subjects, and in smokers and nonsmokers. With adjustment for estimated energy intake, an increase in meat intake of 250 g/d (eg, one steak at approximately 450 kcal) would lead to a 2-kg higher weight gain after 5 y (95% CI: 1.5, 2.7 kg). Positive associations were observed for red meat, poultry, and processed meat. CONCLUSION Our results suggest that a decrease in meat consumption may improve weight management.

Mediterranean dietary pattern and depression: the PREDIMED randomized trial.

BackgroundA few observational studies have found an inverse association between adherence to a Mediterranean diet and the risk of depression. Randomized trials with an intervention based on this dietary pattern could provide the most definitive answer to the findings reported by observational studies. The aim of this study was to compare in a randomized trial the effects of two Mediterranean diets versus a low-fat diet on depression risk after at least 3 years of intervention.MethodsThis was a multicenter, randomized, primary prevention field trial of cardiovascular disease (Prevención con Dieta Mediterránea (PREDIMED Study)) based on community-dwelling men aged 55 to 80 years and women aged 60 to 80 years at high risk of cardiovascular disease (51% of them had type 2 diabetes; DM2) attending primary care centers affiliated with 11 Spanish teaching hospitals. Primary analyses were performed on an intention-to-treat basis. Cox regression models were used to assess the relationship between the nutritional intervention groups and the incidence of depression.ResultsWe identified 224 new cases of depression during follow-up. There was an inverse association with depression for participants assigned to a Mediterranean diet supplemented with nuts (multivariate hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.55 to 1.10) compared with participants assigned to the control group, although this was not significant. However, when the analysis was restricted to participants with DM2, the magnitude of the effect of the intervention with the Mediterranean diet supplemented with nuts did reach statistical significance (multivariate HR = 0.59; 95% CI 0.36 to 0.98).ConclusionsThe result suggest that a Mediterranean diet supplemented with nuts could exert a beneficial effect on the risk of depression in patients with DM2.Trial registrationThis trial has been registered in the Current Controlled Trials with the number ISRCTN 35739639