La Dieta Mediterrània en la DM2. L estudi Predimed

Transcription

1 Dr. María-Isabel Covas Cardiovascular Risk and Nutrition Research Group The REGICOR Study Group IMIM Hospital del Mar Research Institut Barcelona Spain CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) V JORNADES D ACTUALITZACIÓ EN DIABETIS GEDAPS DE LA CAMFIC Barcelona, 28 de Maig del 2013 La Dieta Mediterrània en la DM2. L estudi Predimed (Primary Prevention of Cardiovascular Disease by the Mediterranean Diet)

2 Cardiovascular disease is the main cause of death at the onset of the I Century AMI Stroke AOLLEE Aortic aneurysm

3 BEST WEAPONS AGAINST CARDIOVASCULAR DISEASE: DIET AND EERCISE

4 high intake Traditional Mediterranean Diet

5 moderate and low intake Traditional Mediterranean Diet

6 Mediterranean Food Pattern Rapidly increasing evidence Increased Longevity Prevention of CV mortality Cancer mortality CVD incidence Metabolic syndrome Diabetes Dementia Depression Scarcity of large randomized trials

7 Mediterranean Diet, Risk Factors and Cardiovascular Events after a Heart Attack: Report of the Lyon Diet Heart Study Design Randomized clinical trial on the effects of a Mediterranean-style Diet in a sample of 605 patients who had had a myocardial infarction. Intervention Groups Mediterranean Diet supplemented with margarine enriched with a-linolenic acid (n= 303) Step I Diet of the American Association of Cardiology (n= 302) Follow-up 46 months (Circulation, 1999; 99: )

8 The Effect of the Mediterranean Diet on the Primary Prevention of Cardiovascular Disease.The PREDIMED Study Hospital de Álava de Vitoria Univ Pais Vasco Facultad de Medicina de Navarra Facultad de Medicina de Reus I.C.S.-División Primaria IMIM IDIBAPS-Hospital Clínic Univ.de Barcelona Hospital de Bellvitge Facultad de Medicina de Valencia Hospital Son Espases Univ. Illes Balears Centro de Salud San Pablo Instituto de la Grasa Sevilla Facultad de Medicina de Málaga 19 Research Groups of 7 Spanish Regions 10 Recruitment Centers Universidad de las Palmas de Gran Canaria

9 PREDIMED TRIAL: DESIGN Men: yr Women: yr High CV risk without CVD type 2 diabetics 3+ risk factors Random 1. Smoking 2. Hypertension 3. LDL 4. HDL 5. Overweight/obese 6. Family history CHD

10 PREDIMED Participants Mediet + VOO (n= 2543) MeDiet + Nuts (n=2454) Control (n=2450) Age (SD) 67 (6) 67 (6) 67 (6) Women (%) Diabetes (%) Hypertension (%) Current smokers (%) Dyslipidemia (%) BMI, kg/m 2 (SD) 30 (4) 30 (4) 30 (4) Waist circumf. (SD) 100 (10) 100 (10) 101 (11) Med Diet 0-14 pts. (SD) 8.7 (2) 8.7 (2) 8.3 (2)

11

12

13 PREDIMED INTERVENTION Strategies for behavior change Repeated personal contacts: every 3-mo. Group sessions: every 3-mo. Holistic approach Written information Self-monitoring Individualized goal-setting Quick feedback Individual motivational interviews (every 3-mo.) adapted to the patient s features clinical condition preferences beliefs expressed in servings/d to improve understanding

14 PREDIMED INTERVENTION Strategies for behavior change Additional strategies Seasonal buying lists Menus and recipes Only in the 2 MeDiet groups Provision of key food items for free Control Group: Small gifts non-related with food

15 Results-Adherence to Mediterranean Diet MeDiet (both groups)* Control

16 Adherence to MedDiet plus Virgin Olive Oil intervention

17 Adherence to the MedDiet plus nuts Intervention

18 Odds ratios (ORs) and 95% confidence intervals (CIs) of 1-year reversion among MetS participants and incidence among participants who did not have MetS at baseline (bottom) in the PREDIMED Study (n = 1224) Metabolic syndrome regression Metabolic syndrome development Odds ratio (95% confidence interval) Control group MedDiet + VOO MedDiet + Nuts Salas-Salvadó et al. Arch Int Med, 2008

19 Evidence pro the Mediterranean type Diet Effect of a Mediterranean-Style Diet, on Endothelial Dysfunction, Vascular Inflammation in the metabolic Syndrome. Esposito K, Marfella R, Ciotola M, et al. JAMA 2004;292: Italians with Metabolic Syndrome. 2 years-intervention study. Components Intervention (MedDiet) 2 years Change Control 2 years Change P between of Met S% groups After 2 years,in the intervention group (n=82),only 40 could be 3 31 (34) (66) -17 <0.001 classified as Met S. In control group (n=82), 78 patients 4 10 (11) (13) -4 remained as Met S 5 1(1) -7 7 (8) -1

20 Reduction in the Incidence of Type 2 Diabetes With the Mediterranean Diet Salas-Salvadó J et al. Dia Care 2011;34:14-19 Cumulative diabetes free-survival by group of intervention (n =418 non-diabetic participants) MedDiet+ VOO MedDiet+Nuts MedDiet + VOO =0.49 ( ) MedDiet + Nuts = 0.48 ( ) Low fat diet Adjusted by sex, age, baseline energy intake, BMI, waist circumference, physical activity, smoking status, fasting serum glucose, use of lipid-lowering drugs, MedDiet Score, and weight change during the study Copyright 2011 American Diabetes Association, Inc.

21 Evidence pro the Mediterranean type Diet Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial. Esposito K, et al. Ann Int Med overweight people with newly diagnosed type 2 diabetes who were never treated with antihyperglycemic drugs.4years-intervention study. After 4 years, 44% of patients in the Mediterranean-style diet group and 70% in the low-fat diet group required treatment

22 PREDIMED Steering Committee R. Estruch (chair); D. Corella; M.I. Covas; M.A. Martínez-Gonzalez; E. Ros;J. Salas-Salvadó Projected follow-up = 6 years (median) PREDIMED Independent Data and Safety Monitoring Board avier Pi-Sunyer (chair). Columbia University. USA Carlos A. González. Institut Catalá d Oncologia (ICO), Spain Frank B. Hu. Harvard University, USA Joan Sabaté. Loma Recruitm. Linda University, CA, USA Year % 1 of yr Cum. % recruitment yr yr yr yr yr Interim Analyses with Data until Dec 2010 Total 100

23 Median Follow-up: 4.8 (2.8 to 5.8) Participants: 7447 Intention-to-treat-analyses

24 PRIMARY END-POINT Composite of: Cardiovascular death Non-fatal myocardial infarction Non-fatal stroke SECONDARY END-POINTS Cardiovascular death Non-fatal myocardial infarction Non-fatal stroke Death from any cause Angina leading to revascularization procedure Heart failure

25 Incidence of the Composite Kaplan-Meier Estimates of the Incidence of the Primary End-point Events

26 The PREDIMED Study. Subgroup analyses

27 The PREDIMED Study. Subgroup analyses

28 Mechanisms by which the Mediterranean Diet could exert protective effects

29 Changes in fasting glucose, insulin, and HOMA index after 3- months (n =305 non dibetic participants). The PREDIMED Study * * * * * * Glucose, mg/dl Insulin, pmol/l Homa index (x10) * P < 0.05 versus control -35 TMD+VOO TMD+Nuts Control TMD, traditional Mediterranean Diet; VOO, virgin olive oil Estruch R et al. Ann Int Med 2006

30 Changes in Glucose and Lipid Profile after 3-months (n =772).The PREDIMED Study TMD+VOO TMD+ Nuts Low-fat Glucose Cholesterol 127±44 220±39 121±42 215±37 126±38 213±39 122±38 209±37 133±49 219±40 137±48 221±42 Triglycerides 137±62 133±66 139±63 132±63 147±70 151±80 HDL - cholesterol 44±9 47±10 45±10 46±11 47±10 47±11 LDL - cholesterol 147±35 141±36 140±35 136±33 144±34 145±34 LDL / HDL TMD, traditional Mediterranean Diet; VOO, virgin olive oil p<0.05 Estruch R et al. Ann Int Med, 2006

31 Change % de (%) Cambio Changes in Blood Pressure at 3-month Interventions, (mmhg, N =772). The PREDIMED Study * * * * SBP DBP -5-6 MD+ VOO MD + Nuts Low Fat Estruch R et al. Ann Int Med, 2006 * P < 0.01, 3 mo vs baseline P < 0.001, versus low-fat changes

32 Fitó for the PREDIMED group. Arch Inter Med 2007;167: n = 372 Mediet+VOO=123 Mediet+nuts=128 control=121

33 Changes from baseline in plasma inflammatory biomarkers. The PREDIMED Study (n =772) Changes in ICAM-1 (ng/ml) Changes in CRP (mg/l) Changes in IL-6 (pg/ml) Changes in VCAM-1 (ng/ml) ** MedDiet + VOO MedD + nuts Low fat diet ** * ** ** * ** ** * Estruch et al. Ann Int Med, 2006.

34 Limitations The protocol for the control group was changed halfway through the trial (October 2006). A lower intensity of dietary intervention for the control group during the first few years might have caused a bias toward a benefit in the Mediet groups, since the participants in these groups received a more intensive intervention during that time. However, we found no significant interaction between the period of trial enrollment (before vs. after the protocol change) and the benefit in the Mediet groups.

35 Limitations The generalizability of our findings is limited because all the study participants lived in a Mediterranean country and were at high cardiovascular risk. Whether the results can be generalized to persons at lower risk or to other settings requires further research.

36 Conclusions 1. Among individuals at cardiovascular risk, a traditional Mediterranean diet supplemented with Extra Virgin Olive Oil or with Nuts promoted: 1.1 A 52% reduction of diabetes incidence at a median follow-up of 4 years 1.2 A 30% reduction in the incidence of major cardiovascular events at a median follow-up of 4.8 years

37 Conclusions 2. Results of the PREDIMED Study provide first level evidence on the benefits of the traditional Mediterranean diet on the primary prevention of diabetes and cardiovascular disease.

38 Primary Prevention by the Mediterranean Diet The PREDIMED Study Hospital de Álava de Vitoria Univ Pais Vasco Facultad de Medicina de Navarra Facultad de Medicina de Reus Facultad de Medicina de Valencia I.C.S.-División Primaria IDIBAPS-Hospital Clínic IMIM Univ.de Barcelona Hospital de Bellvitge We thank the participants in the trial for their enthusiastic and sustained collaboration and Joan Vila from Institut Municipal d Investigació Mèdica, Barcelona, for expert Hospital Son Espases Univ. Illes Balears assessment in the statistical analyses. Centro de Salud San Pablo Instituto de la Grasa Sevilla Facultad de Medicina de Málaga Universidad de las Palmas de Gran Canaria

39 ACKNOWLEDGEMENTS Centro de Investigación Biomédica En Red Fisiopatología de la Obesidad y Nutrición Centro de Investigaciones Biomédicas en Red Physiopathology of Obesity and Nutrition. CIBERobn CB06/03 is an initiative of the Instituto de Salud Carlos III. Ministry of Science and Innovation Spanish Network G03/140 AGL ; AGL C03-02/01 AGL C02-01; RETICS RD06/0045/0003 Programa INGENIO CONSOLIDER 2010, FUN-C- FOOD (CSD )

40 THANK YOU FOR YOUR ATTENTION

41 Encuesta de 14 puntos

42

43 Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of all-cause mortality by American Society for Nutrition Sofi F et al. Am J Clin Nutr 2010;92:

44 Forest plot of the association between a 2-point increase of adherence score to the Mediterranean diet and the risk of all-cause mortality by American Society for Nutrition Sofi F et al. Am J Clin Nutr 2010;92:

45 Encuesta de 14 puntos

46 Stratified by recruiting Center and adjusted by age, sex, family history of CHD, smoking, BMI, Waist-to height, and hypertension, dyslipidemia and diabetes at baseline Stratified by recruiting Center and adjusted by age, sex, family history of CHD, and smoking Additionally adjusted by BMI, Waist-to height, and hypertension, dyslipidemia and diabetes at baseline

47 Kaplan-Meier Estimates of the Incidence of Total Mortality MeDiet+EVOO MedDiet+Nuts Low-Fat No. of events: Crude rate/1000 person-yr (95% CI): 10.0 ( ) 11.2 ( ) 11.7 ( )

48 DBP, mmhg SBP, mmhg Systolic and diastolic blood pressure (mean ± s.e.) according to tertiles of in vivo circulating oxidized low density lipoproteins (oxldl) in the PREDIMED population (N=1130) P = for linear trend * Low Medium High P = for linear trend Low Medium High Tertiles of oxldl *P value < 0.01, P value < 0.01 and P value < 0.01 vs. low tertile. Guxens M, et al. Am J Hypertens 2009

49 Metabolic syndrome and Diabetes are associated with elevated circulating oxidized LDL - Metabolic Syndrome + Oxidized LDL Abdominal Obesity Impaired glucose homeostasis Inflammation - Mediterranean Diet Hypertriglyceridemia + Low HDL cholesterol High Blood Pressure - Holvoet P et al. Futur Lipidol, 2008

50 Measurements Eligilibilty questionnaire General questionnaire Follow-up questionnaire Food Freq. questionnaire 14 item score of Med diet Physical activity ques. EKG, BP, and Anthropometric Blood samples Fresh urine sample Toenail sample * Specific measurements Intervention compliance assessment * * Years Urinary tyrosol and hydroxytyrosol Plasma fatty acid composition (oleic and -linolenic acids)