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Introduction: Large randomized trials testing the effect of a multifactorial weight-loss lifestyle intervention including Mediterranean diet (MedDiet) on renal function are lacking. Here, we evaluated the 1-year efficacy of an intensive weight-loss intervention with an energy-reduced MedDiet (erMedDiet) plus increased physical activity (PA) on renal function. Methods: Randomized controlled "PREvención con DIeta MEDiterránea-Plus"(PREDIMED-Plus) trial is conducted in 23 Spanish centers comprising 208 primary care clinics. Overweight/obese (n = 6,719) adults aged 55-75 years with metabolic syndrome were randomly assigned (1:1) to an intensive weight-loss lifestyle intervention with an erMedDiet, PA promotion, and behavioral support (intervention) or usual-care advice to adhere to an energy-unrestricted MedDiet (control) between September 2013 and December 2016. The primary outcome was 1-year change in estimated glomerular filtration rate (EGFR). Secondary outcomes were changes in urine albumin-to-creatinine ratio (UACR), incidence of moderately/severely impaired EGFR (, This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is cofunded by the European Regional Development Fund (5 coordinated FIS projects leaded by J.S.-S and J.V., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926; PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, and PI19/01332); the Especial Action Project entitled Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S.; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to M.Á.M.-G.; the Recercaixa (No. 2013ACUP00194) grant to J.S.-S.; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant; funds from the European Regional Development Fund (CB06/03); International Nut & Dried Fruit Council – FESNAD (Long-term effects of an energyrestricted Mediterranean diet on mortality and cardiovascular disease 2014–2015, No. 201302) (PI: M.Á.M.-G.); the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (PI: D.R.); grant of support to research groups No. 35/2011 (Balearic Islands Gov.; FEDER funds) (J.A.T. and C.B.); the JR17/00022 (ISCIII) grant to O.C.; the Boosting young talent call grant program for the development of IISPV research projects 2019–2021 (Ref.: 2019/IISPV/03 grant to A.D.-L.); the Societat Catalana d’Endocrinologia i Nutrició (SCEN) Clinical-Research Grant 2019 (IPs: J.S.-S. and A.D.-L.). Collaborative Nutrition and/or Obesity Project for Young Researchers 2019 supported by CIBEROBN entitled Lifestyle Interventions and Chronic Kidney Disease: Inflammation, Oxidative Stress and Metabolomic Profile (LIKIDI study) grant to A.D.-L.

Resumen Introduccion y objetivos La estrategia Life's Simple 7 de la American Heart Association propuso 7 metricas de salud cardiovascular ideal: indice de masa corporal (IMC) Metodos La metrica de dieta saludable se definio como alcanzar al menos 9 puntos en una escala validada de 14 puntos de adhesion a dieta mediterranea. Se definio evento cardiovascular mayor incidente como infarto de miocardio, ictus o muerte de causa cardiovascular. Se uso regresion de Cox para estimar hazard ratios (HR) ajustadas multivariables con intervalos de confianza del 95% (IC95%) para categorias sucesivas de metricas de salud cardiovascular. Resultados Tras seguir a 7.447 participantes durante una mediana de 4,8 anos, se registraron 288 eventos. Respecto a los participantes con solo 0-1 metricas, tras ajustar por edad, sexo, centro y grupo de intervencion, se observaron HR (IC95%) 0,73 (0,54-0,99), 0,57 (0,41-0,78) y 0,34 (0,21-0,53), para 2, 3 y 4 o mas metricas respectivamente. Conclusiones En una poblacion espanola con alto riesgo cardiovascular, la presencia de un mayor numero de metricas se asocio progresivamente con una reduccion sustancial en la tasa de eventos cardiovasculares mayores.

Funding sponsor Funding number Acronym Balearic Islands Health Research Institute, EU-COST 35/2011, CA16112, Fondo de Investigación para la Salud, IDISBA CB12/03, CIBEROBN CB06/03, Margalida Comas DG R+D+I, Ministry of Science, Spain, European Commission 201630.10, EAT2BENICE_H2020_SFS2016, European Research Council 2013–2018, 340918, Generalitat Valenciana PROMETEO/2017/017, Instituto de Salud Carlos III, Funding sponsor Funding number Acronym Balearic Islands Health Research Institute EU-COST 35/2011, CA16112 Fondo de Investigación para la Salud IDISBA CB12/03, CIBEROBN CB06/03 Margalida Comas DG R+D+I Ministry of Science, Spain European Commission See opportunities by EC See opportunities (opens in new window) 201630.10, EAT2BENICE_H2020_SFS2016 EC European Research Council See opportunities by ERC See opportunities (opens in new window) 2013–2018, 340918 ERC Generalitat Valenciana See opportunities by GVA See opportunities (opens in new window) PROMETEO/2017/017 GVA Instituto de Salud Carlos III 2013ACUP00194, PI13/00233, PI13/00272, PI13/00462, PI13/00492, PI13/00673, PI13/00728, PI13/01056, PI13/01090, PI13/01123, PI13/02184, PI14/00618, PI14/00636, PI14/00696, PI14/00728, PI14/00853, PI14/00972, PI14/01206, PI14/01374, PI14/01471, PI14/01722, PI14/01919, PI16/00366, PI16/00381, PI16/00473, PI16/00501, PI16/00533, PI16/00662, PI16/01094, PI16/01120, PI16/01522, PI16/01873, PI17/00215, PI17/00508, PI17/00525, PI17/00532, PI17/00764, PI17/00855, PI17/00926, PI17/01183, PI17/01347, PI17/01441, PI17/01732, PI17/01827, PI19/00017, PI19/00309, PI19/00386, PI19/00576, PI19/00781, PI19/00957, PI19/01032, PI19/01226, PI19/01332, PI19/01560, PI20/00138, PI20/00339, PI20/00456, PI20/00557, PI20/00886, PI20/01158, PI20/01532, PI20/01802, Consejería de Salud y Familias, Junta de Andalucía PI0137/2018, PI0458/2013, PS0358/2016

Resumen Introduccion y objetivos Los beneficios cardiovasculares de la dieta mediterranea se han evaluado bajo supuestos de ingesta total de energia ad libitum (sin restriccion de energia). En el presente trabajo se estudia basalmente la cohorte de un gran ensayo en marcha denominado PREDIMED-Plus y la asociacion entre la adherencia a la dieta mediterranea hipocalorica segun la escala de 17 puntos (MedDiet) de este ensayo con la prevalencia inicial de factores de riesgo cardiovascular (FRCV). Metodos Evaluacion transversal de los participantes de PREDIMED-Plus (6.874 adultos mayores con sobrepeso/obesidad y sindrome metabolico). Se evaluo a los participantes para determinar la prevalencia de 4 FRCV (hipertension, obesidad, diabetes, dislipemia). Se estimaron diferencias de medias y razones de prevalencia para FRCV individuales y agrupados con modelos multivariables. Resultados Una mejor adhesion al patron MedDiet se asocio significativamente con niveles mas bajos de trigliceridos, indice de masa corporal y perimetro abdominal. Comparado con una baja adhesion (≤ 7 puntos en el score de 17 puntos), una mejor adhesion a la MedDiet (11-17 puntos) mostro asociaciones inversas con hipertension (razon de prevalencia = 0,97; IC95%, 0,94-1,00) y obesidad (razon de prevalencia = 0,96; IC95% 0,92-1,00), pero se observaron asociaciones positivas con diabetes (razon de prevalencia = 1,19; IC95% 1,07-1,32). Comparado con el tercil mas bajo de adhesion, las mujeres en el tercil superior mostraron un riesgo menor para la agrupacion de 3 o mas FRCV (razon de prevalencia = 0,91; IC95% 0,83-0,98). Conclusiones Entre participantes con alto riesgo cardiovascular, la mejor adhesion a MedDiet se asocio a mejores perfiles lipidicos y medidas de adiposidad, y entre las mujeres mostro asociaciones inversas significativas con la agregacion de FRCV. Este ensayo se registro en 2014 en el International Standard Randomized Controlled Trial Registry (ISRCTN89898870).

Introduction and objectives The cardiovascular benefits of the Mediterranean diet have usually been assessed under assumptions of ad libitum total energy intake (ie, no energy restriction). In the recently launched PREDIMED-Plus, we conducted exploratory analyses to study the baseline associations between adherence to an energy-restricted Mediterranean diet (MedDiet) and the prevalence of cardiovascular risk factors (CVRF). Methods Cross-sectional assessment of all PREDIMED-Plus participants (6874 older adults with overweight/obesity and metabolic syndrome) at baseline. The participants were assessed by their usual primary care physicians to ascertain the prevalence of 4 CVRF (hypertension, obesity, diabetes, and dyslipidemia). A 17-point PREDIMED-Plus score was used to measure adherence to the MedDiet. Multivariable models were fitted to estimate differences in means and prevalence ratios for individual and clustered CVRF. Results Better adherence to a MedDiet pattern was significantly associated with lower average triglyceride levels, body mass index, and waist circumference. Compared with low adherence (≤ 7 points in the 17-point score), better adherence to the MedDiet (11-17 points) showed inverse associations with hypertension (prevalence ratio = 0.97; 95%CI, 0.94-1.00) and obesity (prevalence ratio = 0.96; 95%CI, 0.92-1.00), but positive associations with diabetes (prevalence ratio = 1.19; 95%CI, 1.07-1.32). Compared with the lowest third of adherence, women in the upper third showed a significantly lower prevalence of the clustering of 3 or more CVRF (prevalence ratio = 0.91; 95%CI, 0.83-0.98). Conclusions Among participants at high cardiovascular risk, better adherence to a MedDiet showed significant inverse associations with CVRF among women, and improved lipid profiles and adiposity measures. This trial was registered in 2014 at the International Standard Randomized Controlled Trial Registry (ISRCTN89898870).

BACKGROUND: Type 2 diabetes was related with larger cognitive decline. However, other glycemic dysregulations showed inconsistent results. Our aim was to examine longitudinal associations between diabetes/glycemic status and cognitive function in older adults with metabolic syndrome. METHODS: We conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. Participants were categorized by diabetes status (no-diabetes, prediabetes, and 1c) levels were measured and antidiabetic medications were recorded. Linear and logistic regression models, adjusted by potential confounders, were fitted to assess associations between glycemic status and changes in cognitive function. RESULTS: Prediabetes status was unrelated to cognitive decline. However, compared to participants without diabetes, those with ≥5-year diabetes duration had greater reductions in the GCF (β=-0.11 [95%CI -0.16;-0.06]), processing speed and executive function measurements. Inverse associations were observed between baseline HOMA-IR and changes in the GCF (β=-0.0094 [95%CI -0.0164;-0.0023]), but also between HbA1c levels and changes in the GCF (β=-0.0610 [95%CI -0.0889;-0.0331]), the Mini-Mental test, and other executive function tests. Poor diabetes control was inversely associated with phonologic fluency. Sulfonylureas, but especially insulin use, were related to cognitive decline.CONCLUSIONS: Insulin resistance, diabetes status, longer diabetes duration, poor glycemic control, and insulin treatment were associated with worsening cognitive function at short-term in a population at high cardiovascular risk.TRIAL REGISTRATION: ISRCTN, ISRCTN89898870. Registered 28 May 2014 - Retrospectively registered, http://www.isrctn.com/ISRCTN89898870

Background: Impaired renal function (IRF) in patients with diabetes impose a significant health burden. This study evaluates the association of three diagnostic categories of with a reduction on glomerular filtration rate Methods: We used data from PREDAPS prospective study a cohort of 1072 subjects with prediabetes and another cohort of 772 subjects without prediabetes were follow-up from 2012 to 2017. Prediabetes was defined according to American Association of Diabetes (ADA) criteria. IRF was defined as having a glomerular filtration rate < 60 mL/min/1.73 m2. Incidence rate of IRF according to prediabetes and diagnostic categories of prediabetes as well as Kaplan Meir figures were calculated. Hazard ratios (HR) for the association of the prediabetes diagnostic categories of prediabetes with IRF, adjusting for potential confounders, were estimated by Cox regression models.Results: IRF Incidence rate per 100 person-years in subjects without prediabetes was 1.72 (95% confidence interval [CI]: 1.34-2.21) and 1.79 (95%CI: 1.45-2.20) for those with prediabetes stage, log rank test p= 0.84. Prediabetes was associated with an adjusted HR of IRF onset of 0.76 (95% CI: 0. 54-1.07). Corresponding HR for diagnostic categories were 0.68 (95%CI:0.40-1.15) for those with both altered parameters, 0.68 (95%CI: 00.40-1.15) for those with only impaired HbA1c and 1.12 (95%CI: 0.68-1.85) for those with only impaired FPG. Conclusions: The present study reflects an overall trend towards a slightly decreased risk of IRF onset associated to prediabetes except for individuals with only isolated impaired FPG. Further studies are warranted to fully assess the renal progression of each group.

Background: Healthy lifestyle interventions and drug therapies are proven to have a positive preventative influence on normal glucose regulation in prediabetes. However, little is known on the specific role that these factors play on reversion to normal glycemia according to type of prediabetesMethods: We used data from the Observational prospective cohort study. The Cohort study in Primary Health Care on the Evolution of Patients with Prediabetes from 2012-2015. A total of 1184 individuals aged 30 to 74 years old were included and classified based on the ADA in three mutually exclusive groups using either fasting plasma glucose (FPG) levels (from 100-125 mg/dl, FPG group), HbA1c (5.7%–6.4%, HbA1c group) or both impaired parameters group. Information on lifestyle factors and biochemical parameters were collected at baseline Reversion to normal glucose regulation was calculated at third year of follow-up. Relationship of lifestyle factor and type of prediabetes with reversion were estimated using odds ratios (ORs) with 95% confidence intervals (95% CIs) adjusting by different groups of confounders.Results: Proportion of reversion rates were 31% for FPG group, 31% for HbA1c group and 7.9% for both altered parameters group, respectively. Optimal life style factors such as BMI2[OR (95% CI): 1.90 (1.20-3.01)], high adherence to Mediterranean diet 1.78 (1.21-2.63) and absence of abdominal obesity 1.70 (1.19-2.43) were the strongest predictors for reversion to normal glucose. However, those did not modify the ORs of reversion to normal glucose. Taking as reference those with both impaired parameters, subjects with FPG impairment (FP group) had an OR of 4.87 (3.10-7.65) and 3.72 (2.39-5.78) for HbA1c group. These estimates remained almost the same after further adjustment for biochemical parameters and lifestyle factors (4.55(2.84-7.28) and 3.09 (1.92- 4.97), respectively).Conclusions: Optimal lifestyle factors showed to be a positive predictor for reversion to normal glucose regulation however, the differences of reversion risk according type of prediabetes are not explained by lifestyle factors.

Background & aims: Few studies have compared micronutrient intake and fulfilment of average requirements (EAR) in non-diabetic, pre-diabetic and diabetic adults at high cardiovascular risk. We assessed these variables in a large sample of participants in the PREDIMED-PLUS randomized trial of primary cardiovascular prevention with diet and physical activity. Design: Baseline assessment of nutritional adequacy in n = 5792 men and women, aged 55-75 years, with overweight/obesity and some metabolic syndrome features. Methods: Participants were categorised as non-diabetic (n = 2390), pre-diabetic (n = 1322) or diabetic (n = 2080) by standard criteria. Food and nutrient intake were assessed using a validated food frequency questionnaire. Micronutrients examined were vitamins B1, B2, B3, B6, B12, A, C, D, E and folic acid; Ca, K, P, Mg, Fe, Se, Cr, Zn, and iodine. The proportion of micronutrient inadequacy was evaluated using the EAR or adequate intake (AI) cut-offs. Diet quality was also determined using a 17-item energy-restricted Mediterranean diet (MedDiet) questionnaire. Results: Compared to non-diabetic participants, those with pre-diabetes had lower intakes of total carbohydrates (CHO) and higher intakes of total fat and saturated fatty acids (SFA) and were more likely to be below EAR for folic, while diabetic participants had lower intakes of total CHO and higher intakes of protein, total fat, monounsaturated fatty acids, SFA and cholesterol and were less likely to be below EAR for vitamins B2, and B6, Ca, Zn and iodine. Diabetic participants disclosed higher adherence to the MedDiet than the other two groups. Conclusions: Older Mediterranean individuals with metabolic syndrome and diabetes had better nutrient adequacy and adherence to the MedDiet than those with pre-diabetes or no diabetes. (C) 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

[EN] Introduction and objectives The Life's Simple 7 strategy of the American Heart Association proposes 7 metrics of ideal cardiovascular health: body mass index (BMI) < 25 mg/m2, not smoking, healthy diet, moderate physical activity ≥ 150 min/wk, total blood cholesterol < 200 mg/dL, systolic and diastolic blood pressures < 120 and < 80 mmHg, respectively, and fasting blood glucose < 100 mg/dL. It is important to assess the combined effect of these 7 metrics in the Spanish population. We prospectively analyzed the impact of baseline Life's Simple 7 metrics on the incidence of major cardiovascular events in the PREDIMED cohort (57.5% women, average baseline age, 67 years). Methods The healthy diet metric was defined as attaining ≥ 9 points on a validated 14-item Mediterranean diet adherence screener. An incident major cardiovascular event was defined as a composite of myocardial infarction, stroke, or cardiovascular death. Cox regression was used to calculate multivariable adjusted hazard ratios (HR) and their 95% confidence intervals (95%CI) for successive categories of health metrics. Results After a median follow-up of 4.8 years in 7447 participants, there were 288 major cardiovascular events. After adjustment for age, sex, center, and intervention group, HRs (95%CI) were 0.73 (0.54-0.99), 0.57 (0.41-0.78), and 0.34 (0.21-0.53) for participants with 2, 3, and ≥ 4 metrics, respectively, compared with participants with only 0 to 1 metrics. Conclusions In an elderly Spanish population at high cardiovascular risk, better adherence to Life's Simple 7 metrics was progressively associated with a substantially lower rate of major cardiovascular events., [ES] Introducción y objetivos La estrategia Life's Simple 7 de la American Heart Association propuso 7 métricas de salud cardiovascular ideal: índice de masa corporal (IMC) < 25, no fumar, dieta saludable, actividad física moderada ≥ 150 min a la semana, colesterol total < 200 mg/dl, presión arterial sistólica < 120 mmHg y diastólica < 80 mmHg y glucemia basal < 100 mg/dl. Resulta de gran interés valorar el efecto combinado de estas 7 metas. Se analizó prospectivamente el impacto de las métricas basales Life's Simple 7 en la incidencia de eventos cardiovasculares mayores en la cohorte PREDIMED (el 57,5% mujeres; media de edad inicial, 67 años). Métodos La métrica de dieta saludable se definió como alcanzar al menos 9 puntos en una escala validada de 14 puntos de adhesión a dieta mediterránea. Se definió evento cardiovascular mayor incidente como infarto de miocardio, ictus o muerte de causa cardiovascular. Se usó regresión de Cox para estimar hazard ratios (HR) ajustadas multivariables con intervalos de confianza del 95% (IC95%) para categorías sucesivas de métricas de salud cardiovascular. Resultados Tras seguir a 7.447 participantes durante una mediana de 4,8 años, se registraron 288 eventos. Respecto a los participantes con solo 0-1 métricas, tras ajustar por edad, sexo, centro y grupo de intervención, se observaron HR (IC95%) 0,73 (0,54-0,99), 0,57 (0,41-0,78) y 0,34 (0,21-0,53), para 2, 3 y 4 o más métricas respectivamente. Conclusiones En una población española con alto riesgo cardiovascular, la presencia de un mayor número de métricas se asoció progresivamente con una reducción sustancial en la tasa de eventos cardiovasculares mayores., This study was funded by the Instituto de Salud Carlos III, Spanish Ministry of Health through the support provided to research networks especially developed for the study (RTIC G03/140, to R. Estruch and RTIC RD 06/0045 to M.Á. Martínez González), the Biomedical Research Networking Center for Physiopathology of Obesity and Nutrition, the Spanish National Center for Cardiovascular Research (CNIC 06/2007), Spanish Health Research Fund-European Fund for Regional Development (PI04-2239, PI05/2584, CP06/00100, PI06/00100, PI07/0240,PI07/1138, PI07/0473, PI10/01407, PI10/02658, PI11/02505), Ministry of Science and Innovation (AGL-2009-13906-C02 and AGL-2010-22319-C03), Mapfre Foundation 2010, Regional Health Ministry of Andalusia (PI0105/2007), Public Health Division of the Department of Health of the Generalitat of Catalonia and Generalitat of Valencia (ACOMP06109, GVACOMP201-181,GVACOMP2011-151, CS2010-AP-111, and CS2011-AP-042), and the Regional Government of Navarre (P27/2011).

Background: Healthy lifestyle interventions and drug therapies are proven to have a positive preventative influence on normal glucose regulation in prediabetes; however, there is little evidence to support the role of these factors according to the various stage of the prediabetes stateAims: This study aims to investigate the role of lifestyle factors on the reversion to normal glucose regulation according to the different stage of the prediabetes state based on most up-to-date American Diabetes Association (ADA) guidelines.Design and Setting: Observational prospective cohort study. The Cohort study in Primary Health Care on the Evolution of Patients with Prediabetes from 2012-2015Methods: A total of 1184 individuals aged 30 to 74 years old were included and classified based on the ADA in three mutually exclusive groups using either fasting plasma glucose (FPG) levels (from 100-125 mg/dl, FPG group), HbA1c (5.7%–6.4%, HbA1c group) or both impaired parameters group. Information on lifestyle factors and biochemical parameters were collected at baseline Reversion to normal glucose regulation was calculated at third year of follow-up. Relationship of lifestyle factor and type of prediabetes with reversion were estimated using odds ratios (ORs) with 95% confidence intervals (CIs) adjusting by different groups of confounders.Results: Proportion of reversion rates were 31% for FPG group, 31% for HbA1c group and 7.9% for both altered parameters group, respectively. Optimal life style factors such as BMI2[OR (95% CI): 1.90 (1.20-3.01)], high adherence to Mediterranean diet 1.78 (1.21-2.63) and absence of abdominal obesity 1.70 (1.19-2.43) were the strongest predictors for reversion to normal glucose. ORs of reversion to normal glucose were 4.87 (3.10-7.65) for FPG group and 3.72 (2.39-5.78) for HbA1c group, taking as reference those with both impaired parameters. These estimates remained almost the same after further adjustment for biochemical parameters and lifestyle factors.Conclusions: Although optimal lifestyle factors showed to be a positive predictor for reversion to normal glucose regulation, they do not seem to explain the differences according to the type of prediabetes.

[Background]: Inflammation is known to be related to the leading causes of death including cardiovascular disease, several types of cancer, obesity, type 2 diabetes, depression-suicide and other chronic diseases. In the context of whole dietary patterns, the Dietary Inflammatory Index (DII®) was developed to appraise the inflammatory potential of the diet. [Objective]: We prospectively assessed the association between DII scores and all-cause mortality in two large Spanish cohorts and valuated the consistency of findings across these two cohorts and results published based on other cohorts., [Design]: We assessed 18,566 participants in the “Seguimiento Universidad de Navarra” (SUN) cohort followed-up during 188,891 person-years and 6790 participants in the “PREvencion con DIeta MEDiterránea” (PREDIMED) randomized trial representing 30,233 person-years of follow-up. DII scores were calculated in both cohorts from validated FFQs. Higher DII scores corresponded to more proinflammatory diets. A total of 230 and 302 deaths occurred in SUN and PREDIMED, respectively. In a random-effect meta-analysis we included 12 prospective studies (SUN, PREDIMED and 10 additional studies) that assessed the association between DII scores and all-cause mortality., [Results]: After adjusting for a wide array of potential confounders, the comparison between extreme quartiles of the DII showed a positive and significant association with all-cause mortality in both the SUN (hazard ratio [HR] = 1.85; 95% CI: 1.15, 2.98; P-trend = 0.004) and the PREDIMED cohort (HR = 1.42; 95% CI: 1.00, 2.02; P-trend = 0.009). In the meta-analysis of 12 cohorts, the DII was significantly associated with an increase of 23% in all-cause mortality (95% CI: 16%–32%, for the highest vs lowest category of DII)., [Conclusion]: Our results provide strong and consistent support for the hypothesis that a pro-inflammatory diet is associated with increased all-cause mortality. The SUN cohort and PREDIMED trial were registered at clinicaltrials.gov as NCT02669602 and at isrctn.com as ISRCTN35739639, respectively., Supported by the official funding agency for biomedical research of the Spanish Government, Instituto de Salud Carlos III (ISCIII), through grants provided to research networks specifically developed for the trial (RTIC G03/140, to R.E.; RTIC RD 06/0045, to Miguel A. Martínez-González) and through Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (Proyecto de Investigación (PI) 04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505, PI13/00462, PI13/00615, PI13/01090, PI14/01668, PI14/01798, PI14/01764), Ministerio de Ciencia e Innovación (Recursos y teconologia agroalimentarias(AGL)-2009-13906-C02 and AGL2010-22319-C03 and AGL2013-49083-C3-1- R), Fundación Mapfre 2010, the Consejería de Salud de la Junta de Andalucía (PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (Generalitat Valenciana Ayuda Complementaria (GVACOMP) 06109, GVACOMP2010-181, GVACOMP2011-151), Conselleria de Sanitat y, PI14/01764 AP; Atención Primaria (CS) 2010-AP-111, and CS2011-AP-042), and Regional Government of Navarra (P27/2011).). Drs. Shivappa and Hébert were supported by grant number R44DK103377 from the United States National Institute of Diabetes and Digestive and Kidney Diseases.

Background: Nut consumption has been associated with improved nutrient adequacy and diet quality in healthy adult populations but this association has never been explored in individuals at high cardiovascular risk. Objective: to assess the associations between consumption of nuts and nutrient adequacy and diet quality in a Mediterranean population at high cardiovascular risk. Design: baseline assessment of nutritional adequacy in participants (n = 6060, men and women, with ages 55&ndash, 75 years old, with overweight/obesity and metabolic syndrome) in the PREDIMED-PLUS primary cardiovascular prevention randomized trial. Methods: nut intake was assessed using a validated food frequency questionnaire. Participants who reported consuming zero quantity of nuts were classified as &lsquo, non-nut consumers&rsquo, &lsquo, Nut consumers&rsquo, were participants who reported consuming any quantity of nuts. Nineteen micronutrients were examined (vitamins B1, B2, B3, B6, B12, A, C, D, E and folic acid, Ca, K, P, Mg, Fe, Se, Cr, Zn, and iodine). The proportion of micronutrient inadequacy was estimated using the estimated average requirements (EAR) or adequate intake (AI) cut-points. Diet quality was also assessed using a 17-item Mediterranean dietary questionnaire (Mediterranean diet score, MDS), a carbohydrate quality index (CQI) and a fat quality index (FQI). Results: eighty-two percent of participants were nut consumers (median of nut consumption 12.6 g/day, interquartile range: 6.0&ndash, 25.2). Nut consumers were less likely to be below the EAR for vitamins A, B1, B2, B6, C, D, E, folic acid, and Ca, Mg, Se and Zn than non-nut consumers. Nut consumers were also more likely to be above the AI for K and Cr than non-nut consumers. Nut consumers had lower prevalence of inadequate micronutrient intakes, but also higher CQI, higher FQI, and better scores of adherence to the Mediterranean diet (Mediterranean diet score, MDS). Conclusions: nut consumers had better nutrient adequacy, diet quality, and adherence to the MedDiet than those non-nut consumers.

Background & aims: Legumes, a low-energy, nutrient-dense and low glycemic index food, have shown beneficial effects on glycemic control and adiposity. As such, legumes are widely recommended in diabetic diets, even though there is little evidence that their consumption protects against type 2 diabetes. Therefore the aim of the present study was to examine the associations between consumption of total legumes and specific subtypes, and type 2 diabetes risk. We also investigated the effect of theoretically substituting legumes for other protein- or carbohydrate-rich foods. Methods: Prospective assessment of 3349 participants in the PREvención con DIeta MEDiterránea (PREDIMED) study without type 2 diabetes at baseline. Dietary information was assessed at baseline and yearly during follow-up. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for type-2 diabetes incidence according to quartiles of cumulative average consumption of total legumes, lentils, chickpeas, dry beans and fresh peas. Results: During a median follow-up of 4.3 years, 266 new cases of type 2 diabetes occurred. Individuals in the highest quartile of total legume and lentil consumption had a lower risk of diabetes than those in the lowest quartile (HR: 0.65; 95% CI: 0.43, 0.96; P-trend = 0.04; and HR: 0.67; 95% CI: 0.46–0.98; P-trend = 0.05, respectively). A borderline significant association was also observed for chickpeas consumption (HR 0.68; 95% CI: 0.46, 1.00; P-trend = 0.06). Substitutions of half a serving/day of legumes for similar servings of eggs, bread, rice or baked potato was associated with lower risk of diabetes incidence. Conclusions: A frequent consumption of legumes, particularly lentils, in the context of a Mediterranean diet, may provide benefits on type 2 diabetes prevention in older adults at high cardiovascular risk. Trial registration: The trial is registered at http://www.controlled-trials.com (ISRCTN35739639). Registration date: 5th October 2005., The authors disclose no conflict of interest related with the article. Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds (CB06/03). Supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through grants provided to research networks specifically developed for the trial (RTIC G03/140 and RD 06/0045) through CIBEROBN, and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria–FondoEuropeo de Desarrollo Regional (PI04–2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, and PI11/02505; PI13/00462), Ministerio de Ciencia e Innovación (AGL-2009–13906-C02 and AGL2010–22319-C03), Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (PI0105/2007), Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (ACOMP06109, GVA-COMP2010–181, GVACOMP2011–151, CS2010-AP-111, and CS2011-AP-042), and the Navarra Regional Government (27/2011). The Fundación Patrimonio Comunal Olivarero and Hojiblanca SA (Málaga, Spain), California Walnut Commission (Sacramento, CA), Borges SA (Reus, Spain), and Morella Nuts SA (Reus, Spain) donated the olive oil, walnuts, almonds, and hazelnuts, respectively, used in the study. None of the funding sources played a role in the design, collection, analysis or interpretation of the data or in the decision to submit the manuscript for publication. Acknowledgements: The authors thank all the participants for their collaboration, all the PREDIMED personnel for their assistance and all the personnel of affiliated primary care centers for making the study possible. CIBEROBN is an initiative of ISCIII, Spain.

Background: Few observational studies have examined the effect of dietary fiber intake and fruit and vegetable consumption on total mortality and have reported inconsistent results. All of the studies have been conducted in the general population and typically used only a single assessment of diet. Objective: We investigated the association of fiber intake and whole-grain, fruit, and vegetable consumption with all-cause mortality in a Mediterranean cohort of elderly adults at high cardiovascular disease (CVD) risk by using repeated measurements of dietary information and taking into account the effect of a dietary intervention. Design: We followed up 7216 men (55-75 y old) and women (60-75 y old) at high CVD risk in the Prevención con Dieta Mediterránea (PREDIMED) trial for a mean of 5.9 y. Data were analyzed as an observational cohort. Participants were initially free of CVD. A 137-item validated food-frequency questionnaire administered by dietitians was repeated annually to assess dietary exposures (fiber, fruit, vegetable, and whole-grain intakes). Deaths were identified through the continuing medical care of participants and the National Death Index. An independent, blinded Event Adjudication Committee adjudicated causes of death. Cox regression models were used to estimate HRs of death during follow-up according to baseline dietary exposures and their yearly updated changes. Results: In up to 8.7 y of follow-up, 425 participants died. Baseline fiber intake and fruit consumption were significantly associated with lower risk of death [HRs for the fifth compared with the first quintile: 0.63 (95% CI: 0.46, 0.86; P = 0.015) and 0.59 (95% CI: 0.42, 0.82; P = 0.004), respectively]. When the updated dietary information was considered, participants with fruit consumption .210 g/d had 41% lower risk of all-cause mortality (HR: 0.59; 95% CI: 0.44, 0.78). Associations were strongest for CVD mortality than other causes of death. Conclusion: Fiber and fruit intakes are associated with a reduction in total mortality. PREDIMED was registered at controlled-trials.com as ISRCTN35739639. © 2014 American Society for Nutrition.

Because serum concentrations of soluble forms of TNF-like weak inducer of apoptosis (sTWEAK) and scavenger receptor CD163 (sCD163) have been associated with insulin resistance and type 2 diabetes mellitus (T2D), we tested the associations of sTWEAK and sCD163 with the future development of T2D in elderly subjects at high cardiovascular risk.A prospective, matched case-control study of 153 cases of newly diagnosed diabetic subjects and 306 individually matched controls who did not develop diabetes during a mean 5-year follow-up was conducted using data from the PREDIMED study. Conditional logistic regression was used to estimate the matched odds ratio (OR) for incident T2D according to categories of baseline sTWEAK and sCD163 concentrations measured by ELISA.Baseline sTWEAK concentrations were lower in cases than controls. There were no case-control differences in sCD163 concentrations. In the conditional logistic model that took into account the matching factors, the ORs for T2D incidence in the highest vs the lowest quartile of sTWEAK and the sCD163/sTWEAK ratio were 0.49 (95% confidence interval [CI], 0.31-0.76; P for trend.01) and 1.67 (95% CI, 1.06-2.63; P for trend = .05), respectively. Further adjustment for potential lifestyle confounding factors had little impact on these estimates, whereas adjustment for metabolic syndrome components and fasting insulin levels attenuated the magnitude of associations and only the sTWEAK remained statistically significant (OR = 0.63; 95% CI, 0.40-0.98; P for trend = .05).These findings indicate that in a population at high cardiovascular risk, reduced circulating levels of sTWEAK are associated with an increased risk of diabetes incidence.

Fiber and fiber-rich foods have been inversely associated with cardiovascular disease (CVD), but the evidence is scarce in young and Mediterranean cohorts. We used Cox regression models to assess the association between quintiles of total fiber and fiber from different sources, and the risk of CVD adjusted for the principal confounding factors in a Mediterranean cohort of young adults, the SUN (Seguimiento Universidad de Navarra, Follow-up) cohort. After a median follow-up of 10.3 years, we observed 112 cases of CVD among 17,007 participants (61% female, mean age 38 years). We observed an inverse association between fiber intake and CVD events (p for trend = 0.024) and also between the highest quintile of fruit consumption (hazard ratio (HR) 0.51, 95% confidence interval (CI) 0.27–0.95) or whole grains consumption (HR 0.43 95% CI 0.20–0.93) and CVD compared to the lowest quintile, and also a HR of 0.58 (95% CI 0.37–0.90) for the participants who ate at least 175 g/day of fruit. Only the participants in the highest quintile of fruit-derived fiber intake had a significantly lower risk of CVD (HR 0.52, 95% CI 0.28–0.97). The participants who ate at least one serving per week of cruciferous vegetables had a lower risk than those who did not (HR 0.52, 95% CI 0.30–0.89). In conclusion, high fruit consumption, whole grain consumption, or consumption of at least one serving/week of cruciferous vegetables may be protective against CVD in young Mediterranean populations.

Background Studies evaluating the relationship between soluble transferrin receptor (sTfR), a biomarker inversely related to body iron stores, and risk of type 2 diabetes mellitus (T2DM) are scarce and inconclusive. Furthermore, sTfR concentrations have been observed to be significantly higher in obese than in nonobese individuals. Therefore, the aim of this study was to assess the relationship between sTfR and the risk of T2DM in obese and nonobese subjects. Design A nested case–control study of 153 cases of newly diagnosed diabetic subjects, 73 obese and 80 nonobese, and 306 individually matched controls, 138 obese and 166 nonobese, who did not develop T2DM for a median 6-year follow-up (interquartile range: 3·9–6·5) was conducted using data from the PREvention with MEDiterranean Diet (PREDIMED) cohort (http://www.controlled-trials.com/ISRCTN35739639). Cases and controls were matched for age (≤ 67 vs. > 67 years), gender, dietary intervention group and BMI (≤ 27 vs. > 27 kg/m2). Results Waist circumference is the main determinant of sTfR concentrations in the whole sample (β = 0·476, P < 0·001), in the obese (β = 0·802, P < 0·001) and the nonobese (β = 0·455, P = 0·003). Furthermore, sTfR is directly associated with the risk of T2DM in obese individuals (OR = 2·79; 95% CI: 1·35–5·77, P = 0·005) and inversely associated in nonobese individuals (OR = 0·40; 95% CI: 0·20–0·79, P = 0·015). Conclusions The association between sTfR levels and risk of T2DM in a population at high cardiovascular risk depend on the presence or absence of obesity. While in nonobese subjects elevated sTfR levels are associated with a decreased risk of developing T2DM, in obese subjects the risk increases. This suggests that obesity alters the relationship between sTfR and T2DM incidence.

ResumenLa Asociación Americana de Diabetes ha incluido en 2010 la determinación de la hemoglobina glucosilada (HbA1c) como criterio para el diagnóstico de diabetes con un punto de corte ≥ 6,5%, pero puede tener un porcentaje relevante de falsos negativos. Otras sociedades científicas han aceptado con matices dicho posicionamiento. La HbA1c complementa, pero no sustituye, a la glucemia basal como prueba de cribado y diagnóstico, ni a la determinación de glucosa tras 2 h de la sobrecarga oral de glucosa. La HbA1c no debe emplearse para el diagnóstico de diabetes gestacional. Su interpretación tiene limitaciones en casos de personas con anemias y hemoglobinopatías, por lo que se deben valorar, además de su sensibilidad y especificidad, los costes y el ambiente epidemiológico. ¿Es útil y seguro llevar a nuestros pacientes con diabetes mellitus tipo 2 a valores de HbA1c cercanos a la normalidad? Los resultados de los estudios ACCORD, ADVANCE y VADT son contradictorios y han generado una considerable polémica, pero las prolongaciones de los estudios UKPDS y STENO-2 han demostrado los beneficios de un buen control a largo plazo. Como norma general, parece adecuado un objetivo de HbA1c < 7%. En pacientes con poco riesgo de hipoglucemias, corta evolución de la enfermedad y jóvenes podemos plantearnos una HbA1c < 6,5%. En pacientes con frecuentes hipoglucemias, ancianos o personas con expectativas de vida limitadas serían aceptables cifras superiores al 7%. Este objetivo deberemos conseguirlo mediante un tratamiento individualizado, de inicio temprano, intensivo, seguro y sin riesgo de hipoglucemia, integrándolo en un programa global de prevención de riesgo cardiovascular.AbstractIn 2010, the American Diabetes Association included glycosylated hemoglobin (HbA1c) as a criterion for the diagnosis of diabetes with a cut-off point of ≥ 6.5%. However, there may be a substantial percentage of false negative results. Other scientific societies have accepted this approach but with slight differences. HbA1c complements, but does not substitute, basal glycemia as a screening and diagnostic test or the 2-hour oral glucose tolerance test. HbA1c should not be used for the diagnosis of gestational diabetes.Interpretation of HbA1c is limited in persons with anemia and hemoglobinopathies. Therefore, in addition to its sensitivity and specificity, its costs and the epidemiological situation should also be evaluated. An important question is whether almost normal HbA1c levels are safe in patients with type 2 diabetes. The results of the ACCORD, ADVANCE and VADT trials are contradictory and have aroused considerable controversy. However, the extensions of the UKPDS and STENO-2 studies have shown the benefits of good glycemic control in the long term. As a general rule, a target of HbA1c < 7% seems appropriate.In patients at low risk of hypoglycemic episodes, short disease duration and young persons, HbA1c < 6.5% can be considered. In patients with frequent hypoglycemic episodes, the elderly and persons with short life expectancy, values of more than 7% are acceptable. This target should be achieved through individualized, early, intensive and safe treatment, without risk of hypoglycemia, and should be integrated in an overall program of cardiovascular risk prevention.

To assess the association between the intake of dietary fibre and carotid intima-media thickness (IMT) in a Mediterranean population at high cardiovascular risk.Baseline cross-sectional assessment of 457 men and women (average age 67 years) from two different Spanish centres of the PREDIMED trial. A previously validated food frequency questionnaire (137 food items) was administered by trained dieticians in a face-to-face interview. Mean common carotid IMT was measured using B-mode ultrasound imaging of the right and left carotid arteries by four certified sonographers who used a common protocol. Anthropometric and blood pressure measurements were performed and samples of fasting blood were obtained. Participants were categorized into four groups (roughly quartiles:or =21;21 toor =25;25 toor =31 and31 g/day) of energy-adjusted intake of dietary fibre. Multiple linear regression models were used to adjust for age, sex, centre, smoking, body mass index, diabetes, blood pressure, lipid levels and statin use.In the crude analyses, energy-adjusted fibre intake showed a significant inverse correlation with IMT (r=-0.27, P0.001). In multivariate analyses, a modest, though statistically significant (P=0.03) inverse association between energy-adjusted fibre intake and IMT was also found. The multivariate-adjusted difference in average IMT was -0.051 mm (95% confidence interval: -0.094 to-0.009, P=0.02) for participants whose intake was35 g/day, (n=47) when compared with those whose intake was25 g/day (n=224).Our results suggest that high fibre intake is inversely associated with carotid atherosclerosis.

Fundamento y objetivo El buen control metabolico de los pacientes con diabetes mellitus tipo 2(DM2) disminuira su riesgo de enfermedad cardiovascular (ECV). El objetivo del estudio fue valorarel grado de control glucemico, lipidico y de presion arterial (PA) y describir la prevalenciade hipertension arterial (HTA) y dislipemia de los pacientes con DM2 asistidos en la consultamedica. Pacientes y metodo El TranSTAR es un estudio de casos y controles (emparejados segun sexo yedad), transversal, de ambito nacional realizado on-line. Se recogieron datos sobre glucemiabasal, hemoglobina glucosilada, perfil lipidico, PA y antecedentes personales de ECV y se determinoel valor de la glucemia capilar posprandial (GCPP), entre 1 y 3 h tras la ingesta. Parael estudio del grado de control glucemico, lipidico y de PA de los pacientes con DM2 se aplicaronlas recomendaciones de la Sociedad Espanola de Diabetes. Resultados Se estudiaron 371 parejas de pacientes. En los pacientes con DM2 se observo unmal control glucemico en el 82,1% (intervalo de confianza [IC] del 95%, 77,9–86,3) segun laglucemia basal, en el 88,4% (IC del 95%, 85,1–91,7) segun la GCPP o en el 18,8% (IC del95%, 14,3–23,3) segun la hemoglobina glucosilada. Presento un mal control lipidico el 63,3%(IC del 95%, 56,6–70,0) y un mal control de la PA el 69,5% (IC del 95%, 64,2–74,8). Un9,2% (IC del 95%, 0,9–17,5) y un 20,5% (IC del 95%, 12,8–28,2) presentaban una HTA yuna dislipemia desconocidas, respectivamente. Conclusion La proporcion de pacientes con DM2 que presentan un mal control metabolico esmuy elevada. La disponibilidad de datos obtenidos en nuestra propia poblacion deberia contribuiral mejor tratamiento de los pacientes.

BACKGROUND: The circulating soluble TNF-like weak inducer of apoptosis (sTWEAK) is a cytokine that modulates inflammatory and atherogenic reactions related to cardiometabolic risk. We investigated the association between sTWEAK levels and metabolic syndrome (MetS) and its components in older subjects at high cardiovascular risk. METHODS: Cross-sectional analysis of 452 non-diabetic individuals (men and women aged 55-80 years) at high cardiovascular risk. MetS was defined by AHA/NHLBI and IDF criteria. Logistic regression analyses were used to estimate odds ratios (ORs) for MetS and its components by tertiles of serum sTWEAK concentrations measured by ELISA. RESULTS: sTWEAK concentrations were lower in subjects with MetS than in those without. In gender- and age-adjusted analyses, subjects in the lowest sTWEAK tertile had higher ORs for overall MetS [1.71 (95% CI, 1.07-2.72)] and its components abdominal obesity [2.01 (1.15-3.52)], hyperglycemia [1.94 (1.20-3.11)], and hypertriglyceridemia [1.73 (1.05-2.82)] than those in the upper tertile. These associations persisted after controlling for family history of diabetes and premature coronary heart disease, lifestyle, kidney function and other MetS components. sTWEAK concentrations decreased as the number of MetS components increased. Individuals in the lowest vs the upper sTWEAK tertile had an increased risk of disclosing greater number of MetS features. Adjusted ORs for individuals with 2 vs ≤1, 3 vs ≤1, and ≥4 vs ≤ 1 MetS components were 2.60 (1.09-6.22), 2.83 (1.16-6.87) and 6.39 (2.42-16.85), respectively. CONCLUSION: In older subjects at high cardiovascular risk, reduced sTWEAK levels are associated with MetS: abdominal obesity, hypertriglyceridemia and hyperglycemia are the main contributors to this association.

Background: The traditional Mediterranean dietary pattern (MedDiet) is associated with longevity and low rates of cardiovascular disease (CVD). However, there is little information on who is more likely to follow this food pattern. Aim: To evaluate how different factors are associated with lower MedDiet adherence in older Spanish subjects. Methods: We included 7305 participants (men aged 55-80 y, women 60-80 y) at high-risk of CVD recruited into the PREDIMED trial (ISRCTN35739639). Socioeconomic, anthropometric, lifestyle characteristics and CVD risk factors were recorded. A validated 14-item questionnaire was used to evaluate MedDiet adherence at baseline. Multivariate models were used to estimate odds ratios (OR) and 95% confidence intervals for lower adherence to the MedDiet (, Supported by the official funding agency for biomedical research of the Spanish government, Instituto de Salud Carlos III (ISCIII), through grants provided to research networks specifically developed for the trial (RTIC G03/140, to Dr. Estruch; RTIC RD 06/0045, to Dr. Martinez-Gonzalez and through Centro de Investigacion Biomedica en Red de Fisiopatologia de la Obesidad y Nutricion [CIBERobn]), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigacion Sanitaria-Fondo Europeo de Desarrollo Regional (PI04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, and P11/02505), Ministerio de Ciencia e Innovacion (AGL-2009- 13906-C02, AGL2010-22319-C03 and SAF2009-12304), Fundacion Mapfre 2010, Consejeria de Salud de la Junta de Andalucia (PI0105/2007), Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (ACOMP06109, GVACOMP2010-181, GVACOMP2011-151, CS2010- AP-111, CS2011-AP-042, BEST11-263, BEST/2011/261, GVACOMP2011-151, ACOMP/2011/145 and ACOMP/2012/190), and Regional Government of Navarra (P27/2011). Dr. Toledo is supported by a Rio Hortega post-residency fellowship of ISCIII, Ministry of Economy and Competitiveness, Spanish Government and by the Fundacion Mutua Madrilena. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Treatment of type 2 diabetes in the elderly represents a major challenge both in terms of clinical management and public health. Aging is causing a marked increase in the pandemic of diabetes in elderly people. However, scientific evidence to support the most appropriate treatment for diabetes in the elderly is scarce. Given the heterogeneity of the elderly population, which includes subjects with very different functional and cognitive capacities, co-morbidities, and life expectancy, it is critical to make a comprehensive assessment from a biopsychosocial perspective, to address the vascular risk factors integrally, and to establish individually tailored targets for glycemic control. In frail elderly or individuals with a short life expectancy, it may be reasonable to maintain HbA1c between 7.6%-8.5%. The therapeutic strategy for elderly patients with type 2 diabetes should be individualized and agreed with the patient and their caregivers, according to the objective. Improving quality of life, assuring patient safety and avoiding the adverse effects of antidiabetic treatment should be prioritized. Given the increased susceptibility of the elderly to severe hypoglycemia and its consequences, antidiabetic therapies that minimize the risk of hypoglycemic events should be selected.

In 2010, the American Diabetes Association included glycosylated hemoglobin (HbA1c) as a criterion for the diagnosis of diabetes with a cut-off point of ≥ 6.5%. However, there may be a substantial percentage of false negative results. Other scientific societies have accepted this approach but with slight differences. HbA1c complements, but does not substitute, basal glycemia as a screening and diagnostic test or the 2-hour oral glucose tolerance test. HbA1c should not be used for the diagnosis of gestational diabetes. Interpretation of HbA1c is limited in persons with anemia and hemoglobinopathies. Therefore, in addition to its sensitivity and specificity, its costs and the epidemiological situation should also be evaluated. An important question is whether almost normal HbA1c levels are safe in patients with type 2 diabetes. The results of the ACCORD, ADVANCE and VADT trials are contradictory and have aroused considerable controversy. However, the extensions of the UKPDS and STENO-2 studies have shown the benefits of good glycemic control in the long term. As a general rule, a target of HbA1c7% seems appropriate. In patients at low risk of hypoglycemic episodes, short disease duration and young persons, HbA1c6.5% can be considered. In patients with frequent hypoglycemic episodes, the elderly and persons with short life expectancy, values of more than 7% are acceptable. This target should be achieved through individualized, early, intensive and safe treatment, without risk of hypoglycemia, and should be integrated in an overall program of cardiovascular risk prevention.

Adherence to the Mediterranean diet in patients with type 2 diabetes mellitus and HbA1c level. RATIONALE AND OBJECTIVE: The Mediterranean diet (MeDiet) has beneficial effects on cardiovascular risk factors. We analyzed the association between adherence of a MeDiet in patients with type 2 diabetes mellitus (T2DM) and levels of HbA1c. PATIENTS AND METHODS: This was a cross-sectional study in individuals with T2DM participating in the PREDIMED trial at the centre of Pamplona. Information on diet was collected with a validated 14 point scale of adherence to the MeDiet and blood samples were obtained to assess HbA1c levels. RESULTS: We studied 383 participants with T2DM, 53.4% women (mean age 69 ± 6 years). HbA1c data were available in 262 cases (mean 6.9 ± 1.5%). Although there was a potential inverse non-significant association between adherence to MeDiet and HbA1c levels after adjusting for age and sex, it was not statistically significant. Multivariate analysis additionally adjusted for physical activity, smoking, time of evolution of the T2DM, body mass index and insulin treatment found similar findings (OR = 0.69, 95% CI 0.17-2.83). CONCLUSIONS: Although we found not enough evidence to support that a MeDiet is associated with lower levels of HbA1c in patients with T2DM, our results suggested an inverse trend. Future studies with larger sample size are necessary.

Nutritional markers have several advantages for epidemiologic and clinical assays, when compared to dietary data obtained by food frequency questionnaires. Few studies have assessed whether total polyphenol (TP) compounds provide a valid biomarker for TP intake. To date, there has been almost no literature describing methods to determine TP in complex matrices such as urine, which have many interfering substances. We report a rapid Folin-Ciocalteu method to determine TP in urine samples using Oasis((R)) MAX 96-well plate cartridges for solid phase extraction. These plates allow analysis of a high number of samples at the same time. We performed a prospective, randomized, crossover trial and one cross-sectional study with 60 volunteers from the PREDIMED trial, seeking to evaluate whether the TP in urine were correlated with polyphenol intake and could, therefore, be considered as a marker of intake of these compounds. The assay was optimized; the sensitivity and the polarity range of urine polyphenols were increased and the detection and quantification limits were significantly reduced. The metabolites in standards solution and urine samples were stable under the storage and handling conditions. In the clinical trial and the cross-sectional study, TP excreted in spot urine samples were positively correlated with TP intake, r=0.48, P

Inflammation is involved in cardiovascular diseases. Some studies have found that the Mediterranean diet (MD) can reduce serum concentrations of inflammation markers. However, none of these studies have analyzed the influence of genetic variability in such a response. Our objective was to study the effect of the -765G>C polymorphism in the cyclooxygenase-2 (COX-2) gene and the -174G>C polymorphism in the interleukin-6 (IL-6) gene on serum concentrations of IL-6, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 as well as their influence on the response to a nutritional intervention with MD. An intervention study in a high cardiovascular risk Mediterranean population (314 men and 407 women) was undertaken. Participants were randomly assigned to consume a low-fat control diet or a MD supplemented with virgin olive oil or nuts. Measures were obtained at baseline and after a 3-mo intervention period. At baseline, the COX-2 -765G>C polymorphism was associated with lower serum IL-6 (5.85 ± 4.82 in GG vs. 4.74 ± 4.14 ng/L in C-allele carriers; P = 0.002) and ICAM-1 (265.8 ± 114.8 in GG vs. 243.0 ± 107.1 μg/L in C-carriers; P = 0.018) concentrations. These differences remained significant after multivariate adjustment. The IL-6 -174G>C polymorphism was associated with higher (CC vs. G-carriers) serum ICAM-1 concentrations in both men and women and with higher serum IL-6 concentrations in men. Following the dietary intervention, no significant gene x diet interactions were found. In conclusion, although COX-2 -765G>C and IL-6 -174G>C polymorphisms were associated with inflammation, consuming a MD (either supplemented with virgin olive oil or nuts) reduced the concentration of inflammation markers regardless of these polymorphisms., Supported by grants PI052368, PI051458, PI042234, PI051839, PI052584, PI040233, PI070240, PI070954, G03/140, RD06/0045/0000, RD06/0045/0001, CNIC06, and CB06/03 from the Instituto de Salud Carlos III, Madrid, Spain; by grants GRUPOS2004-43 and ACOMP06109 from the Generalitat Valenciana, Spain; and by grant PI41/2005 from the Navarra Government, Spain.

A good metabolic control of patients with type 2 diabetes mellitus (DM2) will likely contribute to a decrease of their cardiovascular (CV) risk. Our aim was (1) to evaluate the degree of metabolic control with regard to glycemia, lipidemia and blood pressure (BP) and (2) to describe the prevalence of hypertension (HT) and hyperlipidemia in DM2 outpatients.TranSTAR is an on-line, case-control, cross-sectional study, which was performed in outpatient from all around Spain. Data on basal glycemia (BG), glycosilated hemoglobin (A1C), lipid profile, BP and personal history of CV diseases were obtained. The postprandial glycemia (PPG) was measured in a capillary sample at 1-3 hours post-meal. Standards of metabolic control of the Sociedad Española de Diabetes were applied to evaluate the degree of glycemic, lipidemic and BP control.371 pairs of patients were studied. In DM2 patients, a bad control was observed in 82.1% (CI 95%, 77.9-86.3) of them according to BG, in 88.4% (85.1-91.7) according to PPG and in 18.8% (14.3-23.3) according to A1C. An insufficient control in lipid profile was noticed in 63.3% (56.6-70.0) and in BP in 69.5% (64.2-74.8). 9.2% (0.9-17.5) and 20.5% (12.8-28.2) DM2 subjects had an unknown HT and hyperlipidemia, respectively.The rate of DM2 outpatients with a bad metabolic control is very high. The availability of data from our own population should contribute to a better clinical management of these patients.

Objetivo el presente estudio pretende medir el efecto de pioglitazona sobre el riesgo de diabetes mellitus tipo 2 (DM2) y factores de riesgo cardiovascular asociados en adultos con tolerancia alterada a la glucosa (TAG). Diseno se trata de un ensayo clinico controlado, aleatorizado, doble ciego, con empleo de placebo frente a pioglitazona, con una mediana de tiempo de seguimiento de 2,4 anos. La conversion a DM2 se realizo mediante la determinacion de glucosa en ayunas y la practica de una curva de glucemia. El diagnostico se efectuo con la confirmacion de los resultados mediante la repeticion de las pruebas. Emplazamiento 8 centros emplazados en Estados Unidos. Poblacion de estudio se incluyen 602 pacientes con edad ≥ 18 anos, con TAG en una sola curva de glucemia e indice de masa corporal (IMC) ≥ 25. Los pacientes fueron elegibles si su valor de glucemia en ayunas se encontraba entre 95 y 125 mg/dl y al menos otro factor de riesgo de DM2 (apendice). Los criterios se modificaron para incluir a pacientes con valores de glucemia en ayunas de 90–125 mg/dl si en la TAG tenian un valor de glucemia a las 2 h de 170–199 mg/dl con la justificacion de su alto riesgo de desarrollar DM2. La seleccion de sujetos se realizo entre enero de 2004 y marzo de 2006. El seguimiento se realizo hasta la aparicion de DM2 como evento final, abandono del estudio, perdida o hasta completar el estudio. El 58% era mujer y la edad media era de 51 anos en el grupo de piglitazona y de 53 anos en el de intervencion. Tres cuartas partes de los pacientes estudiados tenian un IMC > 30. El 37% del grupo de intervencion y el 40,8% del grupo placebo tenian un IMC > 35. Intervencion los pacientes recibieron inicialmente 30 mg/dia de pioglitazona o placebo. Una vez pasado un mes la dosis se aumento a 45 mg/dia. Tras la aleatorizacion de acuerdo con el centro y el sexo, los participantes recibieron 30 minutos de instruccion sobre dieta con los objetivos del Diabetes Prevention Program, que se reforzo en las visitas de seguimiento. Los participantes volvieron a los 2, 4, 6, 8, 10 y 12 meses durante el primer ano y cada 3 meses a partir de entonces. Se valoro a un total 1.827 pacientes con el fin de determinar si eran elegibles. Se excluyo a 1.225 pacientes, la mayoria de ellos (n = 904) por tener valores de glucemia en ayunas o TAG fuera del intervalo, 187 personas declinaron participar y el resto se excluyo por condicionantes medicos, de comportamiento, logisticos o poco riesgo de DM2. Se asigno de manera aleatoria a 303 a recibir pioglitazona, de los que finalizaron el estudio 213, y 298 fueron incluidos en el grupo que recibio placebo, de los que 228 completaron el estudio. Medicion del resultado una vez seleccionados los pacientes se les realizo una curva de glucemia, con recogida de muestras cada 15 minutos, para la medicion de las concentraciones de glucosa, peptido C e insulina. Tambien se midieron los valores de presion arterial, altura, peso, perimetro de cintura, hemoglobina glucosilada (HbA1c), lipidos y cociente albumina/creatinina entre otras determinaciones analiticas y un electrocardiograma. En 7 centros se realizo un estudio ultrasonografico de alta resolucion en modo B de la arteria carotida comun derecha al inicio y a los 15–18 meses. Se midio tambien la grasa corporal mediante DXA. En cada visita se midieron el peso, la presion arterial y los pulsos, asi como el grado de edema en tobillos. En cada visita se determino la concentracion de glucosa. Cada 3 meses se valoraron los niveles de HbA1c y cada 6 meses, las transaminasas. Anualmente se realizo una curva de glucemia. Resultados principales las tasas de incidencia anual de diabetes fueron del 2,1% en el grupo de pioglitazona y del 7,6% en el de placebo (intervalo de confianza [IC] del 95%, 0,16–0,49; p La conversion a tolerancia oral a la glucosa normal se produjo en el 48% del grupo de intervencion y en el 28% del grupo placebo (p Conclusion en comparacion con el placebo, la pioglitazona reduce el riesgo de conversion de intolerancia a la glucosa a DM2 un 72%, pero se asocia a un incremento significativo del peso y a la presencia de edema.

Objetivo Determinar la influencia de la modificacion de los habitos de vida sobre el desarrollo de diabetes mellitus tipo 2 (DM2) en varones sin intolerancia a la glucosa. Diseno Ensayo aleatorio controlado con un seguimiento de 6 anos. El grupo control recibio la practica clinica habitual Emplazamiento Veintidos centros en Estados Unidos participantes en el estudio Multiple Risk Factor Intervention Trial (MRFIT). Poblacion de estudio Se seleccionaron 12.866 varones de 35 a 57 anos sin antecedentes cardiovasculares procedentes del grupo inicialmente escogido para el estudio MRFIT (361.662). Los participantes debian tener un riesgo cardiovascular superior al 15% para participar en el estudio, y los no fumadores unos valores mas altos de lipidos y presion arterial superior que los fumadores. No se incluyo a pacientes con un peso superior al 150% del que les corresponderia como deseable. Intervencion El estudio se centra en el analisis de los datos de 11.827 individuos sin diabetes o intolerancia a la glucosa al inicio del estudio y de los cuales se disponia de las glucemias durante el seguimiento. Al grupo de intervencion se le dio consejo nutricional y se le animo a reducir el consumo de grasas saturadas y de colesterol y a incrementar el de grasas poliinsaturadas. A los fumadores se les recomendo el cese del habito tabaquico, y a los que tenian mas del 115% de su peso deseable, reducir la ingesta calorica asi como la practica de ejercicio moderado. Si presentaban cifras elevadas de presion arterial, se recomendo dieta hiposodica y perdida de peso. En caso de no lograr reducirlas, se indico tratamiento farmacologico con clortalidona o hidroclorotiazida. Medicion del resultado Se practico a todos una glucemia en ayunas y 1 h tras la ingesta de 75 g de glucosa al inicio y al fin del estudio. Se realizo una revision anual durante al menos 6 anos. Al inicio y en cada revision se pregunto sobre la presencia de diagnostico de diabetes o consumo de antidiabeticos y se realizo una encuesta nutricional de 24 h. Para el diagnostico de diabetes se utilizo la definicion de diabetes establecida por la American Diabetes Association: glucemia en ayunas ≥ 126 mg/dl en cualquiera de los controles anuales o > 300 mg/dl a la hora tras sobrecarga y cuando el paciente informaba del uso de insulina o de hipoglucemiantes orales. Resultados principales El 11,5% de los incluidos en el grupo de intervencion y el 10,8% de los de tratamiento habitual desarrollaron DM2 en 6 anos (riesgo relativo [RR] = 1,08 [intervalo de confianza (IC) del 95%, 0,96-1,20]). En el grupo de intervencion para los fumadores (63%) el RR fue de 1,26 (IC del 95%, 1,10-1,45) y 0,82 (IC del 95%, 0,68-0,98) para los no fumadores (37%). Esta diferencia fue significativa (p = 0,0003). En el grupo de no fumadores el numero necesario para tratar (NNT) fue de 51,5, calculado a partir de los datos del estudio. Conclusion En pacientes no fumadores la intervencion sobre la dieta y el ejercicio, la presion arterial y el colesterol reducen el riesgo de DM2. El cese del habito de fumar y el tratamiento antihipertensivo con diureticos pueden limitar el efecto beneficioso de la dieta y el ejercicio en la prevencion de DM2 en varones sin intolerancia a la glucosa.

BACKGROUND: Eggs are a major source of dietary cholesterol and their consumption has been sometimes discouraged. A relationship between egg consumption and the incidence of cardiovascular disease (CVD) has been suggested to be present exclusively among patients with type2 diabetes. AIMS: To assess the association between egg consumption and CVD in a large Mediterranean cohort where approximately 50% of participants had type 2 diabetes. METHODS: We prospectively followed 7216 participants (55-80 years old) at high cardiovascular risk from the PREDIMED (PREvención con DIeta MEDiterránea) study for a mean of 5.8 years. All participants were initially free of CVD. Yearly repeated measurements of dietary information with a validated 137-item food-frequency questionnaire were used to assess egg consumption and other dietary exposures. The endpoint was the rate of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes). RESULTS: A major cardiovascular event occurred in 342 participants. Baseline egg consumption was not significantly associated with cardiovascular events in the total population. Non-diabetic participants who ate on average >4 eggs/week had a hazard ratio (HR) of 0.96 (95% confidence interval, 0.33-2.76) in the fully adjusted multivariable model when compared with non-diabetic participants who reported the lowest egg consumption (