Obesity, diabetes and metabolic syndrome: the growing epidemic

In part one of a two-part round table, participants discuss evaluation, management strategies and need for greater public awareness.

Cardiology Today convened this round table in November at the American Heart Association Scientific Sessions 2004 in New Orleans.

Seven members of the Cardiology Today Editorial Board participated in a discussion about obesity, diabetes and metabolic syndrome. Chief Medical Editor Carl J. Pepine, MD, moderated the discussion.

Part I of the round table is presented here.
Part II will be published in the March issue of Cardiology Today.

Moderator Carl J. Pepine, MD Eminent Scholar, Professor and Chief, Division of Cardiovascular Medicine, University of Florida, Chief Medical Editor of Cardiology Today.	Franz H. Messerli, MD Director, Hypertension Program, Division of Cardiology, St.Luke's-Roosevelt Hospital, Editor, Cardiology Today’s Hypertension and Vascular Disease section.
George L. Bakris, MD Professor of Preventative Medicine and Internal Medicine, Director, Rush Hypertension/Clinical Research Center, and Member of Cardiology Today's Hypertension and Vascular Disease section.	Rita F. Redberg, MD Professor of Medicine, Director, Women's Cardiovascular Services, University of California San Francisco, Division of Cardiology, and Member of Cardiology Today's Preventive Cardiology section.
Roger S. Blumenthal, MD Associate Professor of Medicine, Director,The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, and Member of Cardiology Today’s Preventive Medicine section.	Udho Thadani, MD Professor of Medicine, Cardiovascular Section, The University of Oklahoma Health Sciences Center, and Member of Cardiology Today’s Cardiovascular Pharmacology section.
Peter Libby, MD Chief, Cardiovascular Medicine, Brigham & Women's Hospital, Mallinckrodt Professor of Medicine, Harvard Medical School, Editor, Cardiology Today’s Vascular Biology section.	Douglas E. Vaughan, MD C. Sidney Burwell Professor of Medicine, Professor of Medicine and Pharmacology & Chief of the Division of Cardiovascular Medicine,Vanderbilt University Medical Center, Member, Cardiology Today's Vascular Biology section.

Carl J. Pepine, MD: Our discussion focuses on the epidemics of obesity, diabetes and metabolic syndrome and the tremendous implications these diseases have on the health of our country as they pertain to cardiovascular disease. To start the discussion, I would like to ask each of you to comment on this topic.

Roger S. Blumenthal, MD: Lewis Kuller, MD, DrPH, from the University of Pittsburgh, spoke about the pathogenesis of metabolic syndrome at a NCEP [National Cholesterol Education Program] meeting two years ago. He said the public health message is that metabolic syndrome refers to pudgy people who need to walk more and eat less. That is really the message that physicians need to get across.

From a therapeutic point of view, we have data that ACE inhibitors and angiotensin receptor blockers [ARBs] probably do a better job of slowing the progression from impaired fasting glucose to diabetes. However, the main message is that there is a great need for better dietary and exercise habits.

Franz H. Messerli, MD: As most of you know, I have practiced medicine in New Orleans for 28 years. The need to eat less and exercise more applies, pretty much, to everyone in the Crescent City. The Lancet has recently stated that the United States is the fattest nation on earth, and another report indicated last year that New Orleans was the fattest city in the United States. In my patient population in New Orleans, between 60% and 70% of patients fulfilled the criteria for metabolic syndrome and between 40% and 50% of them were obese, ie, had a body mass index above 30.

Peter Libby, MD: I have a scientific interest and a public health interest in metabolic syndrome. My scientific work in the last quarter century has concentrated on inflammation. Inflammation is part and parcel of the pathogenesis of metabolic syndrome and may actually provide some clinical tools. We should include a measurement of inflammation in our criteria for diagnosing metabolic syndrome because it will add prognostic value.

From a public health prospective, most of us were brought up in a medical model that deals with disease in a given patient, using a given set of therapeutic tools. I think the epidemic of metabolic syndrome now sweeping our society is something we will not be able to address adequately wearing that single doctor-single patient hat.

We need to address this epidemic as a public health emergency stepping beyond the role of the individual physician and taking a leadership position to halt the spread of obesity and the health risks in its wake. We need to restore physical education in public schools and put resources in education about nutrition. Metaboic syndrome is becoming a pediatric disease, and we are sowing seeds for a very concerning epidemic of cardiovascular morbidity and mortality in the future.

Rita F. Redberg, MD: I agree that metabolic syndrome is now an epidemic. What I find most disturbing is that 40% to 50% of the children in classrooms with my 9- and 11-year-old children probably have metabolic syndrome. I certainly agree that people need to do more walking and less eating. Unfortunately, we are moving in the other direction.

In California, we've cut physical education out of the school system because of the budget crisis. We have also added vending machines with all kinds of sugary stuff in the schools because schools get revenue from those machines. The message we are giving our kids is that it is all right to eat candy and soda in school and that it is all right not to exercise. We are going to see an explosion of diabetes, obesity and cardiovascular disease like we have never seen before.

Douglas E. Vaughan, MD: Metabolic syndrome represents a compound dividend of the impact of excess caloric intake in an increasingly sedentary population. There is a huge impact on potential cardiovascular risk, and that risk is driven by risk factors that are not the same as those commonly seen a generation ago.

Evolving epidemiologic issues are driving the epidemic of metabolic syndrome and cardiovascular disease today – novel thrombotic markers, inflammatory markers and lipids. These risk factors are different than we typically were used to addressing as cardiologists. People need to understand that the risk is real and that the risk is driven by factors that we don't traditionally emphasize.

Udho Thadani, MD: Metabolic syndrome and obesity are self-inflicted problems both by the individual and by the society. It is easy to blame society, but individuals have to take responsibility for it also.

Compared to people in France, Canada or England, the majority of Americans have a huge serving on each plate. Unless we can cut down on our total caloric intake and start walking rather than traveling by car when possible, we are going to have an explosion in the epidemic of obesity and metabolic syndrome. We should have rehabilitation centers and exercise programs in our schools and in the community. Maybe exercise programs can be made mandatory for schools.

Medical treatment should only be considered after lifestyle modifications. We can't and should not start drug therapy for life when we know that lifestyle modification studies have shown that exercise and lowering caloric intake contribute to weight loss.

George L. Bakris, MD: I think there are two issues here. The first issue is that it is nice to put all the onus on the individual, but the individual is only so strong. He can't survive unless the society helps him.

If we look back at the affluent people in Europe in the 1700s and 1800s, we know that they had gout and a lot of health issues. I would be willing to bet that if we could do biochemical profiles on them, metabolic syndrome is nothing new. It is a disease of the affluent. The reason they didn't die of cardiovascular diseases was because they were dying of sepsis.

We need to look at this epidemic in the perspective of the lifestyle that we lead and the demands put on us by that lifestyle. It is impossible for the individual to do it unless he is rich, can afford a trainer and can afford to have Seattle Sutton [that offers cooked and delivered weight-loss meals] send him his food with a prespecified calorie count. That is not practical, but I know one person that actually did that and was very successful.

We also know from papers published in New England Journal of Medicine earlier this year that diets work for a few months, but at the end of the year much of the weight loss is regained.

If we are going to have a real impact, the American Heart Association along with the American Diabetes Association and whoever else wants to come along need to put a unified proposal in front of Congress and say that this is an emergency and we need to do something about it. Then something may happen.

Pepine: What do you use to define obesity in your practice?

Blumenthal: We traditionally use a BMI of greater than 30. However, when Michael Jordan was in his basketball prime, he had a BMI of right around 30, so the definition may vary due to the muscular type of the individual.

For most of us and for the kind of patients that we treat, we use the standard BMI, although we must be aware that in certain men that are athletes and for certain types of body builds, BMI may not be a good assessment.

Pepine: Is there any value to measuring waist circumference?

Redberg: Yes, I think so. We should start using things that are easily accessible such as BMI, waist circumference and waist-to-hip ratio. Waist circumference has been proven in studies to predict cardiovascular disease and metabolic syndrome. In particular, the "apple shape" is associated with metabolic syndrome, meaning a waist circumference of greater than 88 cm in women and greater than 102 cm in men having a very high association. The waist-hip ratio can also be helpful; a ratio greater than 0.85 in women and greater than 0.95 in men is predictive of metabolic syndrome.

Pepine: In your clinic, do you routinely get a BMI or waist circumference for each patient?

Thadani: We weigh the patient and measure height, but we do not routinely measure waist circumference or calculate BMI. While there is a good correlation between BMI and waist circumference, I don't think there is a clearly defined association. Waist circumference is not used for defining obesity; we are talking about the definition of obesity, not metabolic syndrome. Waist circumference is one of the markers used for defining metabolic syndrome.

As far as weight is concerned, some use a weight of greater than 30 kg/m² as a definition of obesity, and some have even suggested anything above 25 kg/m² as the cut-off point. So there are some definition problems of what is overweight vs. what is obese.

Pepine: What should our message be to readers? What should they be recording in their practices to have a simple measure of obesity, or is there no simple measurement?

Bakris: First of all, BMI is not the end all, be all. In fact, there are papers that suggest that BMI can be misleading. Waist circumference is probably better, but waist circumference needs to be measured by someone who is honest and is not the patient.

The patient may say he wears a size 32 pants, but he may be wearing them below the stomach.

Waist circumference indirectly gives you an idea of how much fat is actually there. The enemy here is actually the fat cell in terms of metabolic consequences. So, I do not think there is a simple definition of obesity. We do look at waist circumference, but we measure it in our office. We don't have the patient tell us what size pants he is wearing.

HOMA: homeostasis model assessment used to predict glucose, insulin, C-peptide

The Homeostasis Model Assessment, or HOMA, estimates steady state beta-cell function and insulin sensitivity as percentages of a normal reference population. These measures correspond well, but are not necessarily equivalent, to nonsteady state estimates of beta-cell function (%B) and insulin sensitivity (%S) derived from stimulatory models such as the hyperinsulinemic clamp, the hyperglycemic clamp, the intravenous glucose tolerance test (acute insulin response, minimal model), and the oral glucose tolerance test (0-30 delta I/G). According to the Diabetes Trials Unit at Oxford, United Kingdom, Robert Turner and Rury Holman developed in 1976 the concept that fasting plasma insulin and glucose levels were determined, in part, by a hepatic-beta cell feedback loop. They postulated that elevated fasting glucose levels reflected a compensatory mechanism that maintained fasting insulin levels when there was a reduced insulin secretory capacity, and that fasting insulin levels were elevated in direct proportion to diminished insulin sensitivity. A mathematical feedback model based on these hypotheses was constructed to estimate the degrees of beta-cell function and insulin sensitivity that would equate to the steady state plasma glucose and insulin levels observed in an individual. Model recalibrated The HOMA model developed in 1985 took greater account of peripheral glucose uptake and could use fasting levels of specific insulin or C-peptide in addition to RIA insulin. In 1998, an updated HOMA model (HOMA2) took account of variations in hepatic and peripheral glucose resistance, increases in the insulin secretion curve for plasma glucose concentrations above 10 mmol/L and contribution of circulating proinsulin. The model was recalibrated also to give %B and %S values of 100% in normal young adults when using currently available assays for insulin, specific insulin or C-peptide. The HOMA Calculator is intended for use by health care professionals to assist in the assessment of beta-cell function and insulin sensitivity. It may be of assistance in the management of dysglycemia or Type 2 diabetes but is not a replacement for formal medical assessment and is not intended for use by patients unless in consultation with their trained medical adviser. Information about the calculator and its use is available at http://www.dtu.ox.ac.uk/index.html?maindoc=/homa/.

Pepine: I've been at conferences with nutritionists who look at longitudinal data from our country. I have asked them the question that virtually everyone here touched on: Are we are eating too much and not being active enough?

The reply has been that our caloric intake over previous decades has remained consistent. The big issue is inactivity. How do you react to that?

Bakris: As others have already mentioned, school physical education programs have been cut across the board in this country. More people are living in the suburbs so people are driving more and exercising less. Lifestyle has changed. People are working harder to get the same amount of money and there is less free time to actually exercise. There are many factors.

Thadani: Television is a factor. I heard of a patient who watched six hours of television each day after work. The patient, who was advised to walk around during the advertisements or commercials, lost 7 pounds in a few weeks. So watching television and being a couch potato is a big issue.

Bakris: I had a patient who was similar. All I suggested was that she get the cheapest exercise bike that she could. She watched the same amount of television, but she was on a bike. She lost a lot of weight.

Libby: Data from the Centers for Disease Control and Prevention showed that total caloric intake increased for men from 2,450 in 1971 to 2,618 in 2000. The composition of calories consumed has also changed to more carbohydrates. The food industry began to restrict fat and provide low-fat products that are very high in carbohydrates.

Pepine: I don't think there is any question that the composition of the total caloric intake has changed. I think that is the key.

What is your definition of diabetes?

Thadani: The current definition of diabetes is a fasting glucose equal to or greater than 126 mg/dL, or nonfasting glucose greater than 200 mg/dL. Until recently a fasting glucose level greater than 140 mg/dL was considered as abnormal.

Vaughan: I think those numbers work for the broad population and are effective and pragmatic. There are other ways of diagnosing diabetes using glucose tolerance tests, but I think those fasting glucose criteria work when dealing with patients in everyday life.

Pepine: What is your definition of metabolic syndrome?

Bakris: The definition of metabolic syndrome is the definition that has been published: the criteria of waist circumference, high-density lipoprotein [HDL] cholesterol, lipid parameters and blood pressure and others. The Europeans have added microalbuminuria. With all the data that have come out, microalbuminuria probably should be part of it because it is a nice marker, a simple cheap marker that parallels inflammatory responses.

Metabolic syndrome has a constellation of risk factors, if you really want to look at it that way. If you modify, you are going to reduce risks. Some people have also argued that uric acid should be a part of that group of risk factors. I disagree with that.

Messerli: What about C-reactive protein? Should CRP be a part of that?

Bakris: I would say no. Data coming out of the LIFE trial, for example, looked at microalbuminuria and CRP and showed that even though both microalbuminuria and CRP were predictive of a primary outcome, microalbuminuria was the stronger predictor. It is one thing to talk about metabolic syndrome, but it is another to talk about outcomes.

Libby: The World Health Organization requires measurement of HOMA, the homeostasis model to measure insulin resistance. Then there is the ATP III definition, which is arbitrary – felicitous perhaps – but arbitrary nonetheless. Waist circumference, which is a reflection of obesity, is an ATP III criterion. Maybe the waist circumference should change depending on race.

World Health Organization

American Heart Association

Several data sets show that CRP data add to prognostic information over and above the ATP III criteria for metabolic syndrome. The next step is whether you require measurement of insulin and calculation of HOMA. I think that would be less practical.

The International Diabetes Federation is convening a panel to formulate a global definition of metabolic syndrome. Hopefully, we will converge on a single unified definition of metabolic syndrome rather than having different standards on different sides of the board.

Vaughan: What percentage of people meet the ATP III criteria? There is some movement to include in the definitions an elevated CRP. How does this add to the diagnosis?

Redberg: The problem I have with adding CRP to this definition is that it really is outcome-related. When looking at lipids, HDL and at weight, there are things you can do to reduce your risk. That's not as directly related currently with CRP, and in terms of what we can advise our patients to do, CRP is not adding to that.

Thadani: Should insulin resistance and other descriptors used to define metabolic syndrome by some organizations be included? If you define the syndrome by taking into account the waist circumference, blood pressure, triglycerides and HDL levels, we know that modifying these risk factors does improve the long-term prognosis. High CRP level is a risk marker and adversely influences the prognosis, but we have no data showing that lowering CRP levels improves outcome in patients with metabolic syndrome. On the other hand, we have some outcome data on lifestyle modifications.

Pepine: Which of the two definitions – ATP III or WHO – are you advocating?

Thadani: At the moment we are advocating the ATP III definition, without CRP.

Pepine: How many of you, if you had to choose one to recommend to your readers, would choose WHO or ATP III? I see all of you would choose ATP III. Do you modify that to include CRP?

Blumenthal: You can, but essentially you don't need to have a high CRP to have metabolic syndrome. Even if your CRP is 0.7 or 0.5 and you qualify for metabolic syndrome, it is not going to change the therapy.

Libby: No, but if your CRP is elevated, it does change your cardiovascular risk over and above the existing ATP III definition.

Blumenthal: In The Dallas Heart Study, some of which isn't published yet, they found that the typical African-American woman in Dallas has a CRP of 2.5 or 3.5. So clearly there are differences in CRP between different ethnic groups. Study participants were generally heavier African-American women with poor dietary habits.

I think that the data from the Nurses Health Study and the Women's Health Study show that those CRP values are going to be different than what we see in the Dallas Heart Study and that is something that we have to be aware of.

Libby: That brings me back to what I wanted to say about Dr. Bakris's statement. He said metabolic syndrome is probably not a new disease, that the Georgian patricians had it in their time, which is obviously true. But that sweeps under the rug something we are going to have to confront. Certain minority populations will carry an unfair share of the burden. In the United States, these populations are black and Hispanic; in Asia and the Indian Diaspora, it is the Asian Indian.

Thadani: And it is the American Indians in Oklahoma. There's a huge population of American Indians with diabetes.

Libby: So the genotype is probably important, and the response is environmental factors. The social implications of that vary greatly considering a healthy diet and exercise are not something you can achieve so readily if you are on food stamps and work two jobs. That's why I fear that the medical model will not suffice to confront this epidemic. We need community leadership to try to catalyze a societal change.

Part two will be published in the March issue of Cardiology Today.