sábado, 12 de octubre de 2013

Overweight and Obese Women Are Equally Capable of the Impulse Control That Lean Women Exhibit


Publication Date: 10/9/2013
Dieters call it willpower; social scientists call it delayed gratification.
It’s the ability to delay an immediate reward in favor of a bigger future reward, for example, having a slimmer body in a few months versus the hot fudge sundae now. Previous studies have shown that overweight and obese people have a harder time delaying gratification, so they are more likely to forego the healthy body later on in favor of eating more calorie-dense foods now.
But University at Buffalo research recently published in the journalAppetite now shows that behavioral interventions that improve delay of gratification can work just as well with overweight and obese women as with lean women.
“This research is certainly welcome news for people who have struggled to lose weight, because it shows that when people are taught to imagine, or simulate the future, they can improve their ability to delay gratification,” says renowned obesity expert, Leonard H. Epstein, PhD, SUNY Distinguished Professor in the UB School of Medicine and Biomedical Sciences, who was senior author on the research.
The research is part of a field called prospection, the process by which people can project themselves into the future, by mentally simulating future events.
Some of the most famous research done on delay of gratification includes experiments done at Stanford University in the 1960s and 1970s, where children were given an opportunity to either eat a single snack, such as a marshmallow now, or, if they waited a period of time, they could be rewarded with multiple snacks. Follow-up studies found that in general, those who were able to wait were more responsible and successful in their adult lives.
Epstein notes that many people have difficulty resisting the impulse for immediate gratification. Instead, they do something called delay discounting, in which they discount future rewards in favor of smaller, immediate rewards. This tendency is associated with greater consumption of highly caloric, ready-to-eat foods. It has been speculated that if people could modify delay discounting, they would be more successful at losing weight.
“Now we have developed a treatment for this,” says Epstein. “We can teach people how to reduce delay discounting, where they learn how to mentally simulate the future in order to moderate their behavior in the present.”
The UB researchers evaluated how much delay discounting participants engaged in using a hypothetical test that promised different amounts of money available either now or in the future. While the amount available in the future remained $100, the amount available immediately decreased during each test, eventually falling as low as $1.
Participants were then asked to think about future events that would occur during the time periods involved in the monetary test. So if they were choosing between $95 now and $100 in six months, they would be instructed to think about the most vivid event that would be happening to them six months from now, for example, a birthday party.
A control group was asked, instead, to think during the monetary test of vivid scenes from a Pinocchio story they had read.
The UB researchers found that those who engaged in the future thinking exercise were able to reduce delay discounting and that there were few differences between the lean and the overweight and obese women.
The study looked at 24 lean women and 24 overweight and obese women, all of whom underwent several behavioral assessments to determine differences in each person’s motivation level, their perspective on time and how much they sought out fun and responded to rewards.

In a study published earlier this year, Epstein and his colleagues demonstrated that overweight and obese women ate less when they were imagining themselves in enjoyable future scenarios and reduced their inclination to engage in delay discounting.
“In the current study, we show that episodic future thinking works equally well in overweight and obese women in comparison to lean women,” says Epstein. “That’s important since several studies have shown that overweight/obese women are more impulsive. The fact that projecting oneself into the future and imagining future scenarios works equally well for lean and overweight/obese women is important for designing interventions to reduce impulsive decision making in women who need to lose weight.”

Researchers: Life without Insulin is Possible


Publication Date: 10/7/2013
Several millions of people around the world suffer from insulin deficiencies. Insulin is a hormone, secreted by the beta cells in the pancreas, which plays a major role in the regulation of energy substrates such as glucose. This insufficiency, primarily caused by diabetes (types 1 and 2), has lethal consequences if it is not treated. As of now, only daily insulin injections allow patients to survive.

Several millions of people around the world suffer from insulin deficiencies. Insulin is a hormone, secreted by the beta cells in the pancreas, which plays a major role in the regulation of energy substrates such as glucose. This insufficiency, primarily caused by diabetes (types 1 and 2), has lethal consequences if it is not treated. As of now, only daily insulin injections allow patients to survive. This approach, however, brings on serious side effects. Thanks to their research, which was published in the journal Cell Metabolism, the University of Geneva (UNIGE) scientists identified the underlying mechanisms, proving that life without insulin is possible, and paving the way for new diabetes treatments.

While life without insulin was inconceivable, a group of researchers, led by Roberto Coppari, professor in the Department of Cell Physiology and Metabolism at UNIGE, has just demonstrated that insulin is not vital for survival. By eliminating this dogma, scientists are now considering alternatives to insulin treatment, which poses many risks to patients. An error in dosage may cause hypoglycemia, i.e., a decrease in the level of glucose in the blood, which can lead to a loss of consciousness. In addition, about 90 percent of patients over 55 who have been undergoing treatment for several years develop cardiovascular disease due to elevated levels of cholesterol brought on by the lipogenic properties of insulin.

Leptin Leads to an Essential Discovery
Researchers from UNIGE's Faculty of Medicine conducted experiments on rodents devoid of insulin, to which they administered leptin, a hormone that regulates the body's fat reserves and appetite. Thanks to the leptin, all the subjects survived their insulin deficiency. Using leptin offers two advantages: it does not provoke hypoglycemia and it has a lipolytic effect. 'Through this discovery, the path to offering an alternative to insulin treatment is emerging. Now we need to understand the mechanisms through which leptin affects glucose level, regardless of insulin level,' explains Professor Coppari.

The studies were able to verify whether the neurons involved in the mediation of leptin's anti-diabetic action in healthy mammals played a similar role in rodents suffering from an insulin deficiency. The results showed that this was not the case. In fact, to the scientists' surprise, GABAergic neurons located in the hypothalamus were identified as the main mediators of leptin's action on glucose level in the context of insulin deficiency. These neurons' influence on glucose had never been considered substantial before.

Additionally, the researchers detected the peripheral tissues that are affected by leptin during insulin deficiency. They consist mainly of the liver, the soleus muscle, and brown adipose tissue, which could be directly targeted by future treatments.

Through this discovery, scientists now know where to look for the answer to an insulin-free diabetes treatment. Understanding the functioning and effect of leptin on the body will enable scientists to identify the areas of the body that are involved, and ultimately the molecules that will form the basis of a new treatment.

Type 1 Diabetes and Exercise - 8 Important Points


 By Clara Schneider, MS, RD, RN, CDE, LDN | 10/7/2013

It has been a few years since I met the Olympic swimmer Gary Hall, but the memory is very vivid in my mind. You see, at the time my son was a young teenager swimming on a league team located at a nearby U.S .Army facility. By all accounts not up to an Olympic level, but his swimming dictated our family activities. I also remember two boys with type 1 diabetes on the team trying like my son to win blue ribbons if possible, but also enjoying every aspect of loving their sport. My favorite activity was standing on the side of the pool every Saturday morning, cheering for all the swimmers. My top heroes (of course besides my son) in the athletic world were and still are the three swimmers: Gary Hall and those two young boys.

Meeting Mr. Hall was wonderful for me. It was at the American Diabetes Association Convention. I know there is absolutely no way that he would remember me, but the occasion was an event where his doctor and Mr. Hall discussed his training and managing his type 1 diabetes. I couldn’t get over how lean he was. Here he was a handsome young man with 10 Olympic medals. He was also very gracious. I know my two young friends would love to have his autograph, which he gave with a smile and also for me a hug. What an inspiration! After meeting him, Gary Hall’s picture hung in my diabetes center for the years I directed our program. I would point to the picture when asked if people with type 1 diabetes can exercise and replied, “Yes, of course, with your doctor’s approval.”  “Just look at the picture of Gary Hall,” I would add, “he has type 1 diabetes and worked hard to win 10 medals in the Olympics!”

To my knowledge my other two heroes never went on to the Olympics. They did have a lot in common though with Mr. Hall. They loved their sport and worked hard to keep their diabetes under good control.
 

What are the steps all people with type 1 diabetes should follow so exercise is enjoyed and done safely?

 

Step 1: Think about the kinds of exercise that is necessary for your life and also the exercises you would like to learn, participate in or get better at. Make a list. Items on it may be things like:

- Walk the dog.
- Housework including vacuuming, making beds, and other chores.
- Gardening and lawn work
- Starting a swim program
- Ice hockey
- Soccer
- Cardio-class or yoga at the local community center

Remember this is your list. How are you planning to exercise?

Step 2: Research your exercise. What are the time-periods you are going to devote to exercise? Perhaps you need to walk the dog for 20 minutes 2 times a day. Maybe you are going to join a ice hockey club get up at 4 a.m. for a one-hour practice five days a week and then again at 7 p.m. two days week because that is the ice time your team has. You also plan to play in one-two games over the weekend. Write down the time blocks.

Step 3: See your physician and talk about your lists. Will you be cleared for the exercise? What precautions should you take? Some of these things are the same as everyone else like proper protective gear in sports, but gloves and knee pads may also be appropriate for activities like gardening. What types of foot gear is needed for your exercise? Discussions with your healthcare team may include proper fitting shoes and socks made to keep the feet dry. Talk about taking proper care of your feet to avoid blisters and trauma. Besides wearing a medical ID, what are some important discussion points you need to address with your medical team that are unique to people with type 1 diabetes and exercise?
 

8 Important Points about Type 1 Diabetes and Exercise

 

Point 1: Do I need to adjust my insulin amounts for the activities I choose?How should I do that? Serious athletes may use a pump to regulate their needs for various levels of insulin. When insulin is needed before exercise, it is recommended to inject into subcutaneous tissue that is distal to the exercising muscle. (1) Many people with diabetes have a decrease in their blood sugar although there are people that “go high” with intense exercise. It is important to ask how to adjust your insulin based on your individual needs. It is important to think ahead to avoid hypoglycemia or hyperglycemia.

Point 2: Discuss when you need to test your blood glucose. With all activity is important to test blood glucose before, during and after the activity.  Ask your physician how often you should be testing. Ask what blood glucose readings you should strive for during all three time periods. The exercises you have on your list may affect your blood glucose levels differently. Common recommendations are to have a blood glucose level of at least 100mg/dl before exercising. Is this high enough for you? What does your doctor recommend? If your activity is intense, what should your levels be after exercise? By testing after you exercise you can see the trends of your values and if you need to treat to prevent lows or highs. Exercise can lower your blood sugar for up to 24 hours. (2)

Point 3: What blood glucose and ketone levels indicate that you should not exercise?  General recommendations for people with type 1 are to test blood glucose before exercising. If the levels are above 250 mg/dl but below 300 mg/dl, test for ketones. If ketones are present, do not exercise. The Joslin Diabetes Center recommends: “If there are no ketones present and blood sugars are 300 or more, test within 5-10 minutes of beginning exercise. If your blood sugar is dropping, you may continue. If it is not dropping, stop exercising.” (3) Ask your healthcare team if these guidelines are for you. Also ask for insulin administration and fluid guidelines to help regulate your blood glucose. Test frequently and according to your physicians recommendations. Ask your physician if she/he will write an order for additional strips. Check with your insurance to see what will be paid for.

Point 4: Will your meter readings be affected by factors such as temperature? Know that meter values are influenced by altitude and temperature. If you participate in winter sports, know that circulation to the skin is diminished in the cold. Blood glucose readings taken from the fingertips are not as affected as those taken from other sites. You may see a lag time in your blood sugar of up to an hour at these sites. Normal lag time for alternative sites is 15-30 minutes. (4)  Also know the temperature limits to your meter. Discuss with your healthcare team techniques to keep your meter at the proper temperatures and if you will need to change your meter based on its ability to function. Hints like carrying your meter in the upper inside pocket of your coat may help. Diabetes Forecast has an excellent table of meter limits (both high and low) located here. The guide lists temperatures using the Fahrenheit scale. The equation to compute these values to the Celsius scale, if needed, can be found here.

Point 5: What should I do to take care of my hydration (fluid) needs? The usual rule is to drink fluids before, during and after exercise. A person exercising needs to replace fluids lost from perspiration and to keep hydrated. (5) Recommendations for hydration before and during exercise presented at the Canadian Diabetes Association Professional Conference in 2004 suggests drinking 250ml (approximately 1 cup) of fluid 20 minutes before exercise, and continuing with an additional 250ml for every 20-30 minutes of exercise. (6) Ask your healthcare team what your fluid goals are. Ask what fluids are recommended for you to consume.

Point 6: Discuss how carbohydrates should be consumed before, during and after your exercise. Carbohydrates are usually recommended as part of a meal three-four hours before competitions or one-three hours before exercise. One-hour before competition it may be suggested to drink a sports beverage with 1-2 grams of carbohydrate per kg of body weight. One kg is equal to 2.2 pounds. More carbohydrates needed during exercise are dependent on your blood glucose readings. After exercise it may be suggested to consume slow-acting carbohydrate to protect against post-exercise late-onset. (7) Ask your medical team what is right for you. During exercise you should always have access to a source of simple carbohydrates to handle your blood glucose if it is going low. Discuss with your medical team convenient options.

Point 7: What should I do if I am part of a team to help me keep safe? If you are part of a team or your child with diabetes is part of a team, the National Athletic Trainers' Association (NATA) recommends having a diabetes care plan for practices and games. The care plan is put in place so the appropriate people will know how to take care of the special needs of the athlete with diabetes. For more information, click here.

Point 8: Is there any special equipment I should discuss with my health care team? You may want to consider special equipment based on the exercise you are considering. In swimming, one may want to explore the possibility of a waterproof pump. Other sports may have special needs as well. Explore the possibilities with your healthcare provider.

Exercise should be part of every person’s day. If you have type 1 diabetes, make sure you learn more about the exercise you want to do. Discuss with your medical team if the exercise is something that you can do safely. Maybe some of you with type 1 diabetes reading this article will end up with an Olympic medal or two or even 10 like one of my heroes. All of you should find something that is healthy to participate in like all of my heroes! Do not forget to follow their recommendations of your medical team. Please share with all of us at DiabetesCare.net the exercise you participate in and how you handle any special problems with type 1 diabetes.


Article Reference Links:
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COMMENT ON THIS BLOG POST

martes, 24 de septiembre de 2013

"Tienes que aprender a seguir tu corazón. No puedes permitir que la presión de otras personas haga que tú seas algo que no eres. Si deseas gozar del favor de Dios en tu vida, tienes que ser la persona que Él creó que fueras, no la persona que tu jefe quiere que seas, ni la persona que tus amigos quieren que seas, ni aun la persona que tus padres o tu esposo quieren que seas. No puedes permitir que una expectativa exterior te detenga de seguir tu propio corazón". Joel Osteen
"Siempre debemos estar abiertos y dispuestos a seguir un consejo. Aunque, después de haber orado sobre algo y visto todas las opciones, si todavía no siente paz al respecto, tenga la confianza de tomar la decisión que es la correcta para usted." Joel Osteen

miércoles, 15 de mayo de 2013

Dar un Paso por la Diabetes






 DIABETES: PROTEJAMOS NUESTRO FUTURO

Just 'Weight' Until Menopause -

Just 'Weight' Until Menopause -

Lift Weights to Lower Blood Glucose? -

Lift Weights to Lower Blood Glucose? -

Obesity, Heart Disease Link to High Blood Pressure Identified -

Obesity, Heart Disease Link to High Blood Pressure Identified -

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet


Ramón Estruch, M.D., Ph.D., Emilio Ros, M.D., Ph.D., Jordi Salas-Salvadó, M.D., Ph.D., Maria-Isabel Covas, D.Pharm., Ph.D., Dolores Corella, D.Pharm., Ph.D., Fernando Arós, M.D., Ph.D., Enrique Gómez-Gracia, M.D., Ph.D., Valentina Ruiz-Gutiérrez, Ph.D., Miquel Fiol, M.D., Ph.D., José Lapetra, M.D., Ph.D., Rosa Maria Lamuela-Raventos, D.Pharm., Ph.D., Lluís Serra-Majem, M.D., Ph.D., Xavier Pintó, M.D., Ph.D., Josep Basora, M.D., Ph.D., Miguel Angel Muñoz, M.D., Ph.D., José V. Sorlí, M.D., Ph.D., José Alfredo Martínez, D.Pharm, M.D., Ph.D., and Miguel Angel Martínez-González, M.D., Ph.D. for the PREDIMED Study Investigators

N Engl J Med 2013; 368:1279-1290April 4, 2013DOI: 10.1056/NEJMoa1200303

The traditional Mediterranean diet is characterized by a high intake of olive oil, fruit, nuts, vegetables, and cereals; a moderate intake of fish and poultry; a low intake of dairy products, red meat, processed meats, and sweets; and wine in moderation, consumed with meals.1 In observational cohort studies2,3 and a secondary prevention trial (the Lyon Diet Heart Study),4 increasing adherence to the Mediterranean diet has been consistently beneficial with respect to cardiovascular risk.2-4 A systematic review ranked the Mediterranean diet as the most likely dietary model to provide protection against coronary heart disease.5 Small clinical trials have uncovered plausible biologic mechanisms to explain the salutary effects of this food pattern.6-9 We designed a randomized trial to test the efficacy of two Mediterranean diets (one supplemented with extra-virgin olive oil and another with nuts), as compared with a control diet (advice on a low-fat diet), on primary cardiovascular prevention.

Methods

Study Design

The PREDIMED trial (Prevención con Dieta Mediterránea) was a parallel-group, multicenter, randomized trial. Details of the trial design are provided elsewhere.10-12 The trial was designed and conducted by the authors, and the protocol was approved by the institutional review boards at all study locations. The authors vouch for the accuracy and completeness of the data and all analyses and for the fidelity of this report to the protocol, which is available with the full text of this article at NEJM.org.
Supplemental foods were donated, including extra-virgin olive oil (by Hojiblanca and Patrimonio Comunal Olivarero, both in Spain), walnuts (by the California Walnut Commission), almonds (by Borges, in Spain), and hazelnuts (by La Morella Nuts, in Spain). None of the sponsors had any role in the trial design, data analysis, or reporting of the results.

Participant Selection and Randomization

Eligible participants were men (55 to 80 years of age) and women (60 to 80 years of age) with no cardiovascular disease at enrollment, who had either type 2 diabetes mellitus or at least three of the following major risk factors: smoking, hypertension, elevated low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, overweight or obesity, or a family history of premature coronary heart disease. All participants provided written informed consent.
Beginning on October 1, 2003, participants were randomly assigned, in a 1:1:1 ratio, to one of three dietary intervention groups: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with nuts, or a control diet. Randomization was performed centrally by means of a computer-generated random-number sequence.

Interventions and Measurements


The dietary intervention 8,10-13. The specific recommended diets are summarized in Table 1Table 1Summary of Dietary Recommendations to Participants in the Mediterranean-Diet Groups and the Control-Diet Group. . Participants in the two Mediterranean-diet groups received either extra-virgin olive oil (approximately 1 liter per week) or 30 g of mixed nuts per day (15 g of walnuts, 7.5 g of hazelnuts, and 7.5 g of almonds) at no cost, and those in the control group received small nonfood gifts. No total calorie restriction was advised, nor was physical activity promoted.

For participants in the two Mediterranean-diet groups, dietitians ran individual and group dietary-training sessions at the baseline visit and quarterly thereafter. In each session, a 14-item dietary screener was used to assess adherence to the Mediterranean diet 8,14 so that personalized advice could be provided to the study participants in these groups.
Participants in the control group also received dietary training at the baseline visit and completed the 14-item dietary screener used to assess baseline adherence to the Mediterranean diet. Thereafter, during the first 3 years of the trial, they received a leaflet explaining the low-fat diet on a yearly basis. However, the realization that the more infrequent visit schedule and less intense support for the control group might be limitations of the trial prompted us to amend the protocol in October 2006. Thereafter, participants assigned to the control diet received personalized advice and were invited to group sessions with the same frequency and intensity as those in the Mediterranean-diet groups, with the use of a separate 9-item dietary screener .
A general medical questionnaire, a 137-item validated food-frequency questionnaire,15 and the Minnesota Leisure-Time Physical Activity Questionnaire were administered on a yearly basis.10 Information from the food-frequency questionnaire was used to calculate intake of energy and nutrients. Weight, height, and waist circumference were directly measured.16 Biomarkers of compliance, including urinary hydroxytyrosol levels (to confirm compliance in the group receiving extra-virgin olive oil) and plasma alpha-linolenic acid levels (to confirm compliance in the group receiving mixed nuts), were measured in random subsamples of participants at 1, 3, and 5 years.

End Points

The primary end point was a composite of myocardial infarction, stroke, and death from cardiovascular causes. Secondary end points were stroke, myocardial infarction, death from cardiovascular causes, and death from any cause. We used four sources of information to identify end points: repeated contacts with participants, contacts with family physicians, a yearly review of medical records, and consultation of the National Death Index. All medical records related to end points were examined by the end-point adjudication committee, whose members were unaware of the study-group assignments. Only end points that were confirmed by the adjudication committee and that occurred between October 1, 2003, and December 1, 2010, were included in the analyses. 

Statistical Analysis

We initially estimated that a sample of 9000 participants would be required to provide statistical power of 80% to detect a relative risk reduction of 20% in each Mediterranean-diet group versus the control-diet group during a 4-year follow-up period, assuming an event rate of 12% in the control group.10,17 In April 2008, on the advice of the data and safety monitoring board and on the basis of lower-than-expected rates of end-point events, the sample size was recalculated as 7400 participants, with the assumption of a 6-year follow-up period and underlying event rates of 8.8% and 6.6% in the control and intervention groups, respectively. 
Yearly interim analyses began after a median of 2 years of follow-up. With the use of O'Brien–Fleming stopping boundaries, the P values for stopping the trial at each yearly interim analysis were 5×10−6, 0.001, 0.009, and 0.02 for benefit and 9×10−5, 0.005, 0.02, and 0.05 for adverse effects.18 The stopping boundary for the benefit of the Mediterranean diets with respect to the primary end point was crossed at the fourth interim evaluation; on July 22, 2011, the data and safety monitoring board recommended stopping the trial on the basis of end points documented through December 1, 2010.
All primary analyses were performed on an intention-to-treat basis by two independent analysts. Time-to-event data were analyzed with the use of Cox models with two dummy variables (one for the Mediterranean diet with extra-virgin olive oil and another for the Mediterranean diet with nuts) to obtain two hazard ratios for the comparison with the control group. To account for small imbalances in risk factors at baseline among the groups, Cox regression models were used to adjust for sex, age, and baseline risk factors. We tested the proportionality of hazards with the use of time-varying covariates. All analyses were stratified according to center. Prespecified subgroup analyses were conducted according to sex, age, body-mass index (BMI), cardiovascular-risk-factor status, and baseline adherence to the Mediterranean diet. 

Results

Baseline Characteristics of the Study Participants


From October 2003 through June 2009, a total of 8713 candidates were screened for eligibility, and 7447 were randomly assigned to one of the three study groups . Their baseline characteristics according to study group are shown in Table 2 Baseline Characteristics of the Participants According to Study Group.. Drug-treatment regimens were similar for participants in the three groups, and they continued to be balanced during the follow-up period.

Participants were followed for a median of 4.8 years (interquartile range, 2.8 to 5.8). After the initial assessment, 209 participants (2.8%) chose not to attend subsequent visits, and their follow-up was based on reviews of medical records. By December 2010, a total of 523 participants (7.0%) had been lost to follow-up for 2 or more years. Dropout rates were higher in the control group (11.3%) than in the Mediterranean-diet groups (4.9%). As compared with participants who remained in the trial, those who dropped out were younger (by 1.4 years), had a higher BMI (the weight in kilograms divided by the square of the height in meters; by 0.4), a higher waist-to-height ratio (by 0.01), and a lower score for adherence to the Mediterranean diet (by 1.0 points on the 14-item dietary screener) 

Compliance with the Dietary Intervention

Participants in the three groups reported similar adherence to the Mediterranean diet at baseline and similar food and nutrient intakes. During follow-up, scores on the 14-item Mediterranean-diet screener increased for the participants in the two Mediterranean-diet groups . There were significant differences between these groups and the control group in 12 of the 14 items at 3 years. Changes in objective biomarkers also indicated good compliance with the dietary assignments.
Participants in the two Mediterranean-diet groups significantly increased weekly servings of fish (by 0.3 servings) and legumes (by 0.4 servings) in comparison with those in the control group . In addition, participants assigned to a Mediterranean diet with extra-virgin olive oil and those assigned to a Mediterranean diet with nuts significantly increased their consumption of extra-virgin olive oil (to 50 and 32 g per day, respectively) and nuts (to 0.9 and 6 servings per week, respectively). The main nutrient changes in the Mediterranean-diet groups reflected the fat content and composition of the supplemental foods . No relevant diet-related adverse effects were reported . We did not find any significant difference in changes in physical activity among the three groups.

End Points


The median follow-up period was 4.8 years. A total of 288 primary-outcome events occurred: 96 in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). Taking into account the small differences in the accrual of person-years among the three groups, the respective rates of the primary end point were 8.1, 8.0, and 11.2 per 1000 person-years (Table 3Table 3Outcomes According to Study Group.). The unadjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.70 (95% CI, 0.53 to 0.94) for a Mediterranean diet with nuts (Figure 1Figure 1Kaplan–Meier Estimates of the Incidence of Outcome Events in the Total Study Population.) as compared with the control diet (P=0.015, by the likelihood ratio test, for the overall effect of the intervention).
The results of multivariate analyses showed a similar protective effect of the two Mediterranean diets versus the control diet with respect to the primary end point (Table 3). Regarding components of the primary end point, only the comparisons of stroke risk reached statistical significance (Table 3, and Fig. S6 in the Supplementary Appendix). The Kaplan–Meier curves for the primary end point diverged soon after the trial started, but no effect on all-cause mortality was apparent (Figure 1). The results of several sensitivity analyses were also consistent with the findings of the primary analysis .

Subgroup Analyses


Reductions in disease risk in the two Mediterranean-diet groups as compared with the control group were similar across the prespecified subgroups (Figure 2). In addition, to account for the protocol change in October 2006 whereby the intensity of dietary intervention in the control group was increased, we compared hazard ratios for the Mediterranean-diet groups (both groups merged vs. the control group) before and after this date. Adjusted hazard ratios were 0.77 (95% CI, 0.59 to 1.00) for participants recruited before October 2006 and 0.49 (95% CI, 0.26 to 0.92) for those recruited thereafter (P=0.21 for interaction).

Discussion

In this trial, an energy-unrestricted Mediterranean diet supplemented with either extra-virgin olive oil or nuts resulted in an absolute risk reduction of approximately 3 major cardiovascular events per 1000 person-years, for a relative risk reduction of approximately 30%, among high-risk persons who were initially free of cardiovascular disease. These results support the benefits of the Mediterranean diet for cardiovascular risk reduction. They are particularly relevant given the challenges of achieving and maintaining weight loss. The secondary prevention Lyon Diet Heart Study also showed a large reduction in rates of coronary heart disease events with a modified Mediterranean diet enriched with alpha-linolenic acid (a key constituent of walnuts). That result, however, was based on only a few major events.4,19,20
There were small between-group differences in some baseline characteristics in our trial, which were not clinically meaningful but were statistically significant, and we therefore adjusted for these variables. In fully adjusted analyses, we found significant results for the combined cardiovascular end point and for stroke, but not for myocardial infarction alone. This could be due to stronger effects on specific risk factors for stroke but also to a lower statistical power to identify effects on myocardial infarction. Our findings are consistent with those of prior observational studies of the cardiovascular protective effects of the Mediterranean diet,2,5 olive oil,21-23 and nuts24,25; smaller trials assessing effects on traditional cardiovascular risk factors6-9 and novel risk factors, such as markers of oxidation, inflammation, and endothelial dysfunction6,8,26-28; and studies of conditions associated with high cardiovascular risk — namely, the metabolic syndrome6,16,29 and diabetes.30-32 Thus, a causal role of the Mediterranean diet in cardiovascular prevention has high biologic plausibility. The results of our trial might explain, in part, the lower cardiovascular mortality in Mediterranean countries than in northern European countries or the United States.33
The risk of stroke was reduced significantly in the two Mediterranean-diet groups. This is consistent with epidemiologic studies that showed an inverse association between the Mediterranean diet2,34 or olive-oil consumption22 and incident stroke.
Our results compare favorably with those of the Women's Health Initiative Dietary Modification Trial, wherein a low-fat dietary approach resulted in no cardiovascular benefit.35 Salient components of the Mediterranean diet reportedly associated with better survival include moderate consumption of ethanol (mostly from wine), low consumption of meat and meat products, and high consumption of vegetables, fruits, nuts, legumes, fish, and olive oil. 36,37 Perhaps there is a synergy among the nutrient-rich foods included in the Mediterranean diet that fosters favorable changes in intermediate pathways of cardiometabolic risk, such as blood lipids, insulin sensitivity, resistance to oxidation, inflammation, and vasoreactivity.38
Our study has several limitations. First, the protocol for the control group was changed halfway through the trial. The lower intensity of dietary intervention for the control group during the first few years might have caused a bias toward a benefit in the two Mediterranean-diet groups, since the participants in these two 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 Mediterranean-diet groups. Second, we had losses to follow-up, predominantly in the control group, but the participants who dropped out had a worse cardiovascular risk profile at baseline than those who remained in the study, suggesting a bias toward a benefit in the control group. Third, 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.
As with many clinical trials, the observed rates of cardiovascular events were lower than anticipated, with reduced statistical power to separately assess components of the primary end point. However, favorable trends were seen for both stroke and myocardial infarction. We acknowledge that, even though participants in the control group received advice to reduce fat intake, changes in total fat were small and the largest differences at the end of the trial were in the distribution of fat subtypes. The interventions were intended to improve the overall dietary pattern, but the major between-group differences involved the supplemental items. Thus, extra-virgin olive oil and nuts were probably responsible for most of the observed benefits of the Mediterranean diets. Differences were also observed for fish and legumes but not for other food groups. The small between-group differences in the diets during the trial are probably due to the facts that for most trial participants the baseline diet was similar to the trial Mediterranean diet and that the control group was given recommendations for a healthy diet, suggesting a potentially greater benefit of the Mediterranean diet as compared with Western diets.
In conclusion, in this primary prevention trial, we observed that an energy-unrestricted Mediterranean diet, supplemented with extra-virgin olive oil or nuts, resulted in a substantial reduction in the risk of major cardiovascular events among high-risk persons. The results support the benefits of the Mediterranean diet for the primary prevention of cardiovascular disease.

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