The Doctor Weighs In

By Dov Michaeli MD, Ph.D

In 2005, a team of investigators at the Center for Disease Control and Prevention, or CDC, published a paper that shook the foundations of our long-held beliefs; they found that death rates due to overweight (BMI 25-30) and obesity (BMI >30) were actually lower than death rates due to underweight. The paper came under withering criticism by scientists and nutritionists who had been preaching the gospel of weight control. “Libertarian” organizations funded by the food industry, such as “Food Freedom”, piled on with glee. Their basic message: you can’t trust those scientists; just let the consumer beware (and, I presume, let Darwin and the forces of the “free” market weed out those who did not).

The most serious criticism of the study was that it was not even a prospective study, let alone a controlled one. It had a retrospective design, the least reliable of epidemiological studies. Furthermore, it relied on death certificate reports, notoriously inaccurate and many times misleading. Just as one example, a patient dying of a heart attack would normally have his cause of death listed as myocardial infarction, without mention of the underlying type 2 diabetes. It also flew in the face of a huge body of literature showing excess mortality due to obesity and its link to type 2 diabetes and its cardiac and kidney complications, as well as some of the biggest cancer killers such as colon, breast, esophageal, uterine, ovarian, kidney and pancreas—all obesity related cancers. I might add that recently prostate cancer was added to the list.

In a paper published in the Nov 7 issue of JAMA, the authors of the 2005 study went back to the same data bases they had used, in order to determine which causes of death are associated with underweight and which are associated with overweight and obesity.

The envelope, please…

The group with normal weight (BMI 20-25) were considered the baseline and the groups over or below this range were compared to them.

The diseases associated with overweight and obesity were not surprising; the usual suspects were identified, again: heart disease, kidney disease, type 2 diabetes and cancers related to excess weight.

What is intriguing is the relationship of underweight (BMI less than 18.5) to disease; to my knowledge, this kind of information has not been available before this study was published. These people suffered excessive mortality rates from acute and chronic respiratory disease, injury, as well as some cancers that are not related to excess weight, and miscellaneous other diseases (Alzheimer’s, Parkinson’s).

Critique

The study is revealing, especially in its identification of underweight as not healthy. Jewish and Italian mothers, please stand up and say in unison: I TOLD YOU SO.

What could explain the lower rate of mortality associated with overweight than that associated with underweight? No answer is offered by the survey, but what comes to mind is that modern medicine is simply too good at warding off death. We can now keep patients with heart disease and kidney disease alive with all kinds of wonderful drugs and procedures. Even colon and breast cancers, major killers in the not-too-distant past, are now more like chronic diseases, thanks to early detection, chemo- and biological therapy. And bear in mind: the study measured death rates only; it did not attempt to measure the prevalence of disease that has not resulted in death during the study period. 

What could explain the underweight association with disease? A study of this kind cannot establish causality, but one can speculate (especially when not subjected to the jaundiced eyes of peer reviewers). Two things come to mind: muscle mass and immunity. BMI below 18.5 almost by definition means that some of the lost weight comes from loss of muscle. One of the most important muscles, when it comes to infectious diseases, is the diaphragm. When this muscle is weak, respiration is weak, lungs are not ventilated completely, and before long pneumonia ensues. Bedridden patients, elderly people, patients with AIDS, cachectic (wasted) patients with advanced cancer—all are susceptible to respiratory infections. In fact, this is the most common cause of death in such patients. Likewise, low nutritional status is associated with defective immunity to infectious diseases. But, as I said, this is sheer speculation.

What about the validity of the study as a whole? None of the deficiencies that plagued the original paper, namely retrospective design and reliance on death certificates, have been cured. The methodology is identical, the data base is identical—the only difference is that here we get an analysis of the diseases associated with out- of- the- normal body weights.

Dr, Flegal, the senior author of the study, was quite cautious in her assessment of the study . According to Dr. Flegal, "The take-home message is that the relationship between fat and mortality is more complicated than we tend to think." On the other hand, experts like Walter Willett, professor of epidemiology and nutrition at the Harvard School of Public Health, "dismissed the findings as fundamentally flawed, saying [that] an overwhelming body of evidence has documented the risks of being either overweight or obese." He called the findings "rubbish."

Well, well, I wouldn’t go that far. The study did contribute some valuable information on underweight and its relationship to disease. And it provoked controversy—which is great; this is how science is done and how progress is made.

By Dov Michaeli MD, Ph.D

If you are a woman, you don’t have to read on. But if you are a man, I mean a real one, with a prostate, this is for you.

An Article in the Feb 15, 2007 issue of Cancer by Wright, Chang, Schatzkin, et al. has some disturbing news for obese men; They have a higher risk of dying from prostate cancer than men of normal weight. The study, called the NIH-AARP Diet and Health Study, found that men who reported weight gain after age 18 (!) were also found to be at increased risk of dying from prostate cancer. These findings did not change when age, family history of prostate cancer, race, or past screening history were accounted for. The most likely explanation underlying the observed association is that heavier men have hormonal alterations that adversely affect prostate cancer progression leading to death.

A total of 287,760 male study participants were included in this analysis. Men were between 50 and 71 years of age at the start of the study in 1995-1996, at which time they filled a questionnaire that asked about the height, weight, and other factors, as well as cancer screening practices. The authors of this study looked at body mass index (BMI), which was calculated from height and weight. They also examined weight change from age 18 years to baseline (1995-1996). Approximately 29% of men were classified as normal weight (BMI <25 kg/m²), 50% as overweight (BMI 25-29.9 kg/m²), and 21% as obese (BMI >30 kg/m²). During five years of follow-up, 9,986 cases of prostate cancer were identified. During six years of follow-up, 173 prostate deaths occurred.

Critique

This study had several strengths, including the large number of men with prostate cancer, a wide range of reported weights, and the ability to determine if any other factors affected the association between BMI and prostate cancer risk. This last statement is especially important, since studies of this sort are susceptible to what we call “confounding factors”, meaning that other factors, not the ones studied, may account for the results. Having participated in the study (as a subject), I can verify that the investigators left no stone unturned. I remember thinking, as I filled out the exhaustive, and exhausting, questionnaire that the only thing they left out was asking about the phase of the moon on the day I was born.

The study results add to the growing evidence that obesity increases the risk of fatal prostate cancer. What is alarming is that this prospective study identified increasing weight after age 18 as a risk factor for prostate cancer death.

What about women?

No, I am not talking about women with a prostate gland. Rather, about obese women’s susceptibility to cancer. Indeed, there is compelling evidence that these women are indeed at higher risk of dying of breast cancer. And this is not surprising at all. The adipose tissue in men can synthesize a close relative of testosterone, which can fuel the growth of cancerous prostate tissue. Likewise, adipose tissue in females can synthesize a close derivative of estradiol, a hormone stimulating the growth of breast cancer.

Why do we see younger adults with breast and prostate cancer?

At least for men, this study offers an explanation. We now know that weight gain after age 18 can affect a person’s risk of getting prostate cancer. We also know, from other studies, that chronic exposure to testosterone (or its adipose-synthesized derivative) is carcinogenic, and will accelerate the onset of the malignant process. That may explain why we see now men in their 30s and 40s with prostate cancer.

We also know that women with a long term exposure to estrogen have a higher risk of developing cancer of the breast. This is why women who have children at a later age are more susceptible to breast cancer than women who had children early and often. And early obesity may be the reason why we see now women in their 30s with breast cancer.

Should this finding be used in a public campaign to combat obesity among our teenagers? I think so.

Dov Michaeli MD, Ph.D is in the biotech industry

By Dov Michaeli MD, Ph.D

Here is some exciting news from the Biotech world: the time is fast approaching when your personal DNA sequence will be readily available.

So what’s the big deal? Read on.

The human genome project

In 2003, the first complete genetic blueprint was published with great fanfare (President Bush, believe it or not, was present at the announcement). At the time, scientific pundits, journalists, and self-appointed crystal ball-gazers, fell over each other proclaiming the benefits of this scientific feat. Indeed, the possibilities were, and still are, simply huge. People expected the advances to come tumbling down almost immediately; it did not happen. Why? Money! It cost about 3 billion dollars to complete the first sequencing in 2003. At that price, it would have cost about $900 billion to sequence everybody's DNA in the US. Come to think of it, that’s not that much more than the Iraq war is costing us…

Fortunately, bright and competent people are engaged in this enterprise. The J. Craig Ventner Institute announced two months ago that it had completed the sequencing of, well, J. Craig Ventner’s genome. Cost: $60 million, or 2% of the cost of the original Human Genome Project’s DNA sequence.

Want more? There are now at least four companies that are racing to develop machines that will sequence a person’s genome for $10,000, or 0.017% of the cost for the Ventner sequence. In fact, the first one to reach the mark will win a $10 million prize offered by the X Prize Foundation. At this price we could have everybody’s DNA sequenced for a total national cost of $3 billion—chump change, about 2 week’s worth of a dirty little war.

What’s the big deal about sequencing everybody’s DNA?

For this you have to understand what DNA is made of. It is made of 4 chemicals, or bases, A, T, G, and C, strung together. Every three bases code for an amino acid, and those, strung together, make up the proteins that carry out all the functions that keep us alive and well. The sequence of these bases, and hence the equence of the amino acids they code for, is highly variable.  So, to be able to read the genomic blueprint, you have to determine the sequence in which they appear. The number of possible permutations in the order in which the bases, and amino acids, is arranged  is essentially infinite.There are about 100 million bases in a chromosome, and there are 23 chromosomes—so you can appreciate the enormity of the task.

But you can appreciate another fact. No system is 100% error-free. As they say in Washington, mistakes have been made. The mistakes in the formation of the DNA, for instance T instead of a G in a particular place, are actually quite common. They are called single nucleotide polymorphisms or SNP (pronounced ‘snips’, aka ‘point mutations’), and they are responsible for our individuality. This is why my daughter and son share a lot of traits with me and their mother, but are not identical to either one of us, and are not even ‘an average’ between the two of us. They are truly unique. This is also the reason why the fear that people will clone their offspring, or the DNA of some famous people, in order to obtain a perfect replica, is misplaced—they will never get it thanks to SNPs (and thank God, or evolution, for that). The first and last individual to come close was Narcissus—and look what happened to him: he became something else—a flower (called narcissus). Not even close.

As part of our personality/ individuality SNPs determine something important: our susceptibility to various diseases and our tolerance of different drugs. For instance, Ventner discovered from his DNA that he has a certain gene variant that increases his susceptibility to Alzheimer’s disease. Other variants are associated with cardiovascular disease, diabetes, basically all human diseases. Mind you, we are not saying that people with SNPs predisposing them to obesity will become obese. But they are predisposed to obesity, and most likely will have to work harder to ward it off.

Now you can begin to see the revolutionary importance of having a complete map of your DNA.

• You, and your physician, will know ahead of time what incipient diseases are lurking in the dark recesses of your genome. You can then take action. To avoid type 2 diabetes you can control your diet. To avoid heart disease you could adhere to a diet and exercise regime, get more frequent checkups, maybe even start on low dose aspirin as a preventative measure. The same goes for cancers, psychiatric disorders, etc, etc.
• Or consider this: we'll be able to tell which child really suffers from ADHD or bipolar disorder, and who is just ' being a kid'; no more fuzzy and subjective diagnoses, especially in psychiatry.
• We now know, from a field called pharmacogenomics, that people respond differently to different drugs. This too is controlled to a large extent by your SNPs. Some people take a drug called methotrexate for treatment of their cancer or rheumatoid arthritis and tolerate it without much of a problem. Others experience extreme fatigue, nausea, vomiting, anemia, infections and other unpleasant side effects. The answer my friend is written in the SNPs.
• There are certain drugs that work in some people and not at all in others. One of those is a cancer drug called 5FU, another is the anti acid drug Zantac. I still remember that many years ago the Japanese government refused to approve it in Japan unless the drug company conducted extensive clinical trials in Japan, because "the Japanese GI tract is different". We attributed it to plain old protectionism. It turned out that many Japanese indeed react to the drug differently—because of a unique combination of SNPs.
• Psychiatric drugs are currently prescribed on a hit or miss basis. Some patients go through four or five drugs, different doses of each, combinations of drugs etc. until the desired effect is achieved. Why is this great variability? you guessed it. Knowing the patient’s genetic makeup ahead of time could avoid this terrible process of trial and error.

I could go on and on, because the list is endless. But you get the idea.

The Pharmaceutical Industry

The business model of the drug industry depended on the discovery of blockbuster drugs, selling for billions of dollars a year. The industry is now changing its collective thinking. They realize that to make money they don’t have to treat millions and millions of people; they could make it by focusing on a much smaller population, and deliver a drug that is essentially tailor-made for it. The up front expense of clinical trials is enormous. The reason is that if the drug works on say, 50% of the people, you need many thousands of subjects enrolled in the trial in order to show a significant effect of the drug. But if you knew ahead of time the genetic makeup of the people who are likely to respond to the drug- then you’ll need only dozens, or a few hundred at most, to show the effect. The tremendous reduction in the cost of such a trial would make even a drug that is effective in only10% of the population highly profitable.

This is not a theoretical model anymore, it actually happened. A small percentage of patients with chronic myelogenous leukemia (CML) have a certain constellation of SNPs in an enzyme that is central to the disease. The drug company, Novartis, decided to develop a drug that would be specific for these people. They saw it as a public service rather than a commercial undertaking. The drug, called Imatinib, was tested in the first phase of the trial in about 25-30 patients, to prove its safety. But lo and behold, it was also 100% effective. On this basis the FDA quickly approved it. The company did not have to spend hundreds of millions of dollars and 15 years to bring it to market. This made it a very profitable drug.

The sociological effect

Without getting too deeply into the implications of these developments, here is a thought: we faithfully repeat the mantra that we are all unique individuals. Some truly believe in it, others (especially people in power) pay lip service to the concept, but in reality expect everybody to behave the same. Just ask any teacher who has to deal with a bright, but restless, child. Or the police officer who has no time or patience for idiosyncratic behavior. Or the despot who brooks no dissent. But once the concept of uniqueness of the individual ceases to be just a philosophical idea and becomes rooted in our Biology, maybe, just maybe, we’ll learn to accept our fellow humans as uniquely individual, deserving of all the legitimacy and respect we’d accord to ourselves.

Now that would be a paradigm shift!

By Dov Michaeli MD, Ph.D

Leptin is a hormone secreted from fat cells that provides information to the brain about energy stores. If energy stores are abundant, circulating levels of leptin are high, and the brain’s response is reduced food intake. On the other hand, in the fasted state leptin levels are low, and the response is increased food intake. It had been known that the regions of the brain where leptin exerts its influence are the nucleus accumbens and the associated nerve bundles called the striatum, regions where the reward/pleasure centers are located (and are the seat of addiction as well). However, there is little or no information about how these  brain centers integrate leptin’s signal with the rewarding properties of food.

Now a group of scientists from Cambridge university in the UK provided the missing link. In a paper published recently in Science they report on a study done on a 14 year-old boy and a 19 year-old girl who suffered from a very rare condition of leptin deficiency. This condition causes hyperphagia or excessive eating and gross obesity. But when they were injected with synthetic leptin eating was reduced to about normal levels. The investigators used fMRI (functional MRI) to visualize the nucleus accumbens and striatum. They presented the subjects with visual images of food, and for control-- visual images of non-food, in the leptin-deficient and leptin-treated states. They used a 10-cm visual analog scores to rate hunger, satiety, and the “liking” of the various food images.

And the results…

What they have shown is that leptin markedly affects neural responses to visual food stimuli; the appropriate reward centers showed markedly elevated blood flow, indicating increased metabolic activity in those regions. The responses to the questionnaire rating hunger, satiety and “liking” of the food images indicated that leptin did not affect the “liking” but rather the “wanting” of food. In the leptin-deficient state, images of well-liked foods engendered a greater wanting response, even when the subject had just been fed. After leptin treatment, well-liked food images engendered this response only in the fasted state. Thus, wanting of food appears to drive the correlation between activation of the reward centers and liking.

Why is it important?

At first blush, the whole exercise looks like splitting hairs: what difference is there between wanting and liking a food? My son used to hate anything that lived in water. But when he was famished enough he wolfed down a salmon steak and asked for more. In neurobiological terms, his low leptin level told his brain: you want this fish, liking it is not an issue right now. Which reminds me of a conversation I had with an orthodox rabbi about arranged marriages. What about love, I asked. That will come after the wedding, he answered.

From an evolutionary point of view it makes a lot of sense. Roaming the Savannah in search of food after several days of fasting there is no advantage in being too choosy; just give me that piece of meat, and I don’t care where it came from. I suspect that liking a certain food is a relatively recent addition to our behavioral repertoire, after the invention of agriculture about 10,000 years ago and the availability of reliable and abundant supply of food. Before that we didn’t eat—we devoured.

Dov Michaeli MD, Ph.D is in the Biotech industry, and he really likes good food.

By William H. Bestermann Jr. MD

Type 2 diabetes is a condition that costs Americans terribly in terms of death, disability, and health care expenditures. This chronic condition is a vicious cycle type of illness. Glucose control tends to deteriorate over time. Most of these patients also have problems with blood pressure and cholesterol. Only about a third of type 2 diabetics have their pressure, sugar, or cholesterol under control as individual risk factors. Only 7% have all three risk factors controlled simultaneously to conservative goals. This sad fact has dramatic consequences. The lifetime risk of a diabetic having a heart attack or a stroke is 80%. For each risk factor that is controlled to goal using the right medication, the risk is reduced by roughly half—so when we control pressure, sugar, and cholesterol the risk is reduced from 80% to 40% to 20% to 10%. Now maybe the risk is not really 10%, but it is very dramatically reduced and in 10 years of experience with 450 diabetics, I believe that I have seen a very important reduction in vascular events that has been achieved by aggressively controlling these risk factors..

Everything bad that happens to a diabetic is fundamentally arterial or vascular. Obviously the heart attacks, strokes and amputations are vascular, but even the kidney, nerve and eye damage relate to arterial damage as well. So the target here is not just the sugar or the cholesterol. The fundamental question is “how do we lower the sugar, cholesterol and pressure with the maximum benefit on the artery?” Furthermore, how do we accomplish this in such a way that the patient’s life is minimally altered and this is sustainable.

In this post, I will focus on sugar control. Everyone agrees that type 2 diabetes is at its core a life-style illness. As one of my colleagues in South Carolina said: “There is nothing that we can do for diabetes that you cannot outrun with a spoon.” In other words, if the patient does not make some effort with diet and exercise, it is difficult and perhaps impossible to get risk factors to goal. I have controlled the sugar in disabled patients, but it is more difficult. Type 2 diabetes is a disease of elevated blood sugar. It is self-evident that sugar consumption must be limited. Less widely appreciated is the impact of starch or carbohydrate consumption. Processed starch becomes sugar in 2 minutes once it is consumed. When a person eats 100 calories of white rice, in 2 minutes it is just as if he took a spoon and ate 100 calories of sugar out of the sugar bowl. The less processed a carbohydrate, the more slowly it is consumed.

Some understanding of nutrition is vital. Formal dietary instruction by a certified diabetic instructor is helpful but I see substantial variation in what patients are told. As a practical matter I have found the South Beach diet to be very useful and just bought the book for a friend at Walmart for $12.00. I have recommended that diet for patients and found it very effective with sustainable effects on weight and sugar control. Dr Agatson, the author, is a cardiologist famous for developing the cat scan calcium score we use to determine cardiac risk. He teaches two very important concepts. First, we have to learn to limit starch and to eat our starch in the form of whole foods. Second, we need to limit fats, especially animal fats and trans fat. This program is attractive because it is effective, widely available, and supported by recipe books and pre-packaged items.

Next we come to drug therapy. Doctors are trained in the treatment of diabetes with medication by learning about all of the medications that are available, and then they are left to decide which of these many medications they will use and in what order. There are several different classes of oral drugs with multiple drugs in each class. There are multiple types of insulin with differing durations of action. There is no real protocol that is universally agreed upon as best practice.

Type 2 diabetes is the later stage of the metabolic syndrome. Most type 2 diabetics have been metabolically abnormal for decades. They have been resistant to the effects of insulin for years and just before they become diabetic they have been maintaining their normal sugar by producing levels of insulin in the blood that are three times normal. As time goes on they are unable to sustain that level of insulin production and when insulin levels fall the sugar begins to rise. At the time of diagnosis, insulin production has fallen by 50% and the loss of the ability to produce insulin is aggravated by poor sugar control—a built-in vicious cycle. When it comes to diabetes, we just do too little too late.

In recognition of this fact, there was a recent consensus algorithm published in Diabetes Care. This is a joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. They emphasized the importance of diet and exercise as first therapy. Most notably in my view the authors went on to say, “The authors recognize that for most individuals with type 2 diabetes, lifestyle interventions fail to achieve or maintain metabolic goals, either because of failure to lose weight, weight regain, progressive disease, or a combination of factors. Therefore, our consensus is that metformin therapy should be initiated concurrent with lifestyle intervention at diagnosis.” Most medications for diabetes cause weight gain. Metformin has modest effects in assisting with weight reduction and it is the only medical treatment for diabetes that is proven to lower the incidence of heart attack and stroke by 40%. That effect is on a par with the best cholesterol and pressure treatments.

If treatment with metformin fails, it is generally because insulin production is at least relatively inadequate. The most effective and rational next step is to instruct the patient in a self-adjusted insulin shot using Lantus or Levemir. In the protocol I use, the patient is able to rapidly bring the sugar safely down and most patients are at goal with this reasonably simple approach. It seems to me that the proven vascular benefits of metformin would be preserved in these patients since all we are doing is replacing insulin that they cannot make themselves. Most patients are really surprised at how easy this is to work with and how much better they feel when their sugar is controlled.

Brian Klepper 

Over at Health Care Policy and Marketplace Review, the always insightful Bob Laszewski drew my attention to the release of a new report from The Trust for America's Health , F as in Fat: How Obesity Policies Are Failing in America. This 120 page document, funded by the Robert Wood Johnson Foundation, provides an update on how obesity is ravaging America's health and productivity.

The facts about America's obesity problem aren't new.  They continue to be grim and worsening:

• Two thirds of American adults are now overweight or obese.
• Adult obesity rates exceed 20 percent in 47 states.
  
• In the past year,  the obesity rates increased in 31 states; no state improved
  
• Obesity is at the root of an array of our most expensive major diseases that will generate huge costs for care and lost productivity.
• 85 percent of Americans believe obesity is a national epidemic.
• So far, neither Congress nor our nation's business leaders have recognized this problem as a priority or developed a comprehensive plan to combat it.

Mr. Laszewski rightly argues that the insidious nature of this problem warrants national action, and that we should develop a pro-health/anti-obesity campaign that follows the example of the very successful anti-smoking campaign a few years back. Absolutely true.

While The Trust for America's Health (TFAH) report is honest and an honorable effort at consciousness-raising, I'm afraid I found their approach and call-to-action disappointingly vanilla and almost certainly ineffectual.  TFAH focuses primarily on describing community-based programming that might promote healthy habits and discourage bad ones.

This is fine, I guess, as far as it goes, but it is a form of passive resistance that doesn't really acknowledge or address corporate money and influence as at least partial roots of the problem. Except for a couple quick references, this report doesn't really dwell on the fast, prepared and junk food industries, on the advertising techniques used to seduce children and adults, or on the business leadership that will be required to turn this around.

Mr. Laszewski refers us to the work of Ken Thorpe, an Emory University health economist who has done a good deal of work on the relationship between obesity and health care cost. He quotes Dr. Thorpe:

"The obesity epidemic has caused a tenfold increase in the nation's private health insurance bill for conditions related to being overweight, according to a self-funded study by researchers with the Emory University Rollins School of Public Health. According to the study the cost of treating conditions linked to obesity increased from $3.6 billion to $36.5 billion between 1987 and 2002. The study concludes that the best way to lower healthcare spending is to target the rise in population risk factors -- especially obesity."

"Current approaches to controlling healthcare costs are not working because they ignore the true drivers of those costs,' Dr. Thorpe says. 'Increases in the number of people getting treatment for serious health problems like diabetes, heart disease, high cholesterol and mental disorders are directly linked to population increases in obesity. If insurers and employers are serious about reining in health care spending, then obesity prevention should be at the top of their agenda."

In a recent post, I recounted how a good friend, a preventive cardiologist, told me that, when it came to my body's propensity to lay down plaque in my vessels, I wasn't taking the problem seriously. That woke me up, and I've made a lot of efforts since then to turn the problem around.

The junk food problem is obvious and, in a sense, no less dangerous to the nation's welfare than if it were crack cocaine. It will drain our financial resources and cripple the nation's ability to be productive. Under our form of government, where lobbying dollars drive how policy works, the answer is clear. Our business leaders can take this problem seriously, overwhelm the food industry's behaviors, and reshape policy to diminish the impact of advertising and make healthy living a positive cultural value. Or we can surrender the nation to the pushers who feed our addiction. It really isn't a lot more complicated than that.

I have spent a good deal of my career synthesizing the terrific information created by researchers and translating it to decision-makers. At some point, problems and their solutions become extremely well understood, and further efforts to describe the problem are, in a sense, superfluous.

Like the larger health care crisis, the obesity crisis is now very well understood. While updates on the status of the issue are always welcome, what is really needed is a deeper understanding of the problem's power dynamics, and the formulation of mobilization plans to address them. If we don't intend to address the obesity problem directly - at the level of corporate power and influence - then all the updates in the world won't matter.

Brian Klepper (904.246.9643 o, bklepper@gmail.com) is a health care analyst and advisor based in Atlantic Beach FL. 

by Pat Salber, MD

While not nearly as high profile as TV’s “The Biggest Loser,” the National Weight Control Registry has helped researchers gain a better understanding of what it takes to lose a significant amount of weight (at least 30 pounds) and keep it off (for at least a year).

The Registry was started in 1994 by Rena Wing, Ph.D. from Brown Medical School, and James O. Hill, Ph.D. from the University of Colorado. According to the NWCR website, it is the largest prospective investigation of long-term successful weight loss maintenance in the country.  Individuals who meet the criteria of “successful losers” self-report information about their dietary, exercise, and other lifestyle habits. Although not a randomized, controlled clinical study (the “gold standard” in research), there is nevertheless some valuable information to be gleaned from this weight control registry.

According to results reported by lead investigator, Suzanne Phelan, PhD, at the June 2-5, 2007 Endocrine Society meetings in Toronto, 89% of 4,200 registry participants lost weight with diet and exercise. Ten percent used diet alone and 1% exercise alone. The average age of the losers was 47 years old; 77% were female, 95% Caucasian, 64% married and 82% college-educated.

Nearly half the registrants lost weight on their own, not relying on outside help such as weight loss programs or counselors. Strategies included restricting certain foods, such as deserts (87%), portion control (44%); counting calories (43%), counting fat grams (25%), and using liquid meal-replacements (20%).

The August 2007 issues of DOC News, a publication of the American Diabetes Association, reports that Phelan and her team identified a number of other key strategies:

• Low cal, low fat. Participants reported an average energy intake of about 1,300 calories per day with about 20-30% of those calories from fat. To put this in perspective, this is about the amount of calories you get when you lunch on a Big Mac with medium fries and a Coke.
• Lots of physical activity. These losers reported burning about 2,600 calories per week (walking 5 miles or engaging in 30-90 minutes of physical activity per day).
• Limited TV viewing. More than half of the participants watched fewer than 10 hours of TV per week. Only 21% watched more than 21 hours weekly. The average American watches about 28 hours/week. [Note: Not only did these folks have more time to exercise, they also may have been able to avoid the compulsive eating associated with eating while viewing.]
• Frequent self-weighing. Seventy-five percent reported weighing at least once a week. Forty-four percent weighed daily and 31% weekly.   Click here for more information on this important weight control behavior.
• Dietary consistency. Participant tended to eat the same type and amount of food on weekends and holidays as during the work week.
• Limited dietary variety. Many participants restricted their choices within food groups.
• Don’t skip breakfast. Almost 80% of participants reported eating breakfast every day.
• Limited fast food. Participants rarely ate fast food – consuming less than one such meal per week (see bullet one to see why this is important!)

National Weight Control Registry participants did not take their weight loss and maintenance for granted. They had to work at it. But they did report that the perception of the effort required decreased over time. It becomes a way of life.

If you are interested in learning more about the National Weight Control Registry visit www.nwcr.ws/ . If you are a successful loser, consider becoming a registrant - help contribute to our national knowledgebase of what it takes to take it off and keep it off.

by Pat Salber, MD

The cabbie who drove me from the airport to the hotel on my last business trip probably weighed 400 pounds.  We made small talk during the trip.  He told me he was hoping to leave Nevada soon and move to Oregon.  But, he said, it was tough getting the time and resources to make the move.

He works 12 hours days, six days a week.  The cab company deducts chunks of his pay  for their share of his revenues and to cover his health insurance premium and a tax on his tips.  His take home pay is $500 every two week pay period.

As we started talking about his health insurance, the conversation naturally drifted to health.  He is prediabetic, he told me, and his brother is a type 2 diabetic who has already had some toes amputated.  He knows he is facing the same future if he doesn't lose weight, but how can he do it?

When you drive a cab 12 hours a day, you often eat on the run.  That means fast food, high fat, and lots of calories.  Also, how do you fit in exercise?  Should he try to walk before the 12 hour shift or, perhaps, go out in the middle of the night when his shift is over? 

I found myself wondering what I would do if I were his doctor.  Of course, I would recommend he lose weight, alot of it.  And, I would tell him to get moderate to vigorous exercise 30 to 60 minutes a day.  I would prescribe any needed medications.  And, I would tell him to join WeightWatchers, or better yet an on-line weight loss support program, like PEERtrainer (www.peertrainer.com).

Chances are, in my 15 minute office visit, I wouldn't have learned about the challenges presented by his daily schedule.  I wouldn't understand that my recommendations were unlikely to be followed -- not because he wouldn't, but rather because he couldn't.

If something doesn't change, his prediabetes will most likely become diabetes.  He will probably have a heart attack or stroke or maybe, like his brother, he will end up with toes or feet amputated -- all potentially preventable if he could change his lifestyle.

At the end of the ride, all I could think of to say was that he needed to get a new job -- one that is less stressful and would allow him to exercise and eat better.  But I knew this too would be a daunting task given the long hours he already works and the meagerness of his financial resources.

I keep mulling over his story and wondering, how could you help this man?  I haven't come up with an answer.  Can you?

This is an oldie, but goodie, first published on TDWI September 15, 2006

by Bill Besterman

The underpinning for much of the death and disability from arterial vascular disease in this country is the metabolic syndrome. One of the real authorities on the metabolic syndrome is a Dr. Ralph DeFronzo.  I particularly like his description of this collection of disorders as a “complex metabolic web.” 

The patients who have this diagnosis are burdened with multiple chronic conditions: hypertension, high LDL or bad cholesterol, high triglycerides, low HDL or good cholesterol, and high blood sugar ultimately resulting in type 2 diabetes. These patients routinely have vascular systems where the vessels are inflamed and the blood more likely to clot.

Early in the condition the arteries are thicker and less distensible than in people without the syndrome; progression of the arterial disease is the norm. Many of affected individuals also have gout. More recently, the metabolic syndrome has been called the cardiometabolic syndrome because this name underscores the impact of these conditions on the heart and the rest of the vascular system. Metabolic syndrome patients have an increased risk of coronary artery disease, cardiac enlargement and congestive heart failure.  Type 2 diabetes is the late stage of the syndrome

Dr. DeFronzo highlights a very important clinical reality in describing the cardiometabolic syndrome as a complex metabolic web. "Job one" of the clinicians who treat these patients is to unravel that complex web using every medical and lifestyle tool in the medical toolbox.

Only 7% of these patients have all of their risk factors (hypertension, blood sugar, and cholesterol) simultaneously controlled to the most conservative goals. For each risk factor that is controlled, using the proper interventions, the risk of all adverse outcomes is reduced by roughly 50%. So, the task of the clinician is not just to control hypertension or diabetes, but rather to control all risk factors to goal at the same time.

That is where the focus, skill and training of your provider come into play. The particular medical choices that are made are critical for success. For three decades now I have heard physicians blame patients for not being “compliant:”

 “Mrs. Brown is diabetic and she does not listen to a thing I tell her. She just stuffs herself with anything she wants and she continues to gain weight.”

Here is the reality. Every medication commonly used for the treatment of type 2 diabetes causes weight gain with the exception of metformin (Glucophage) and the Byetta-type medications. The new drug Januvia is weight neutral. Most patients do not have their sugar controlled to goal using a single medication. Most patients require multiple drugs and even then progressive loss of glucose control is the norm. Weight gain not only makes control of the sugar more difficult—the metabolic syndrome is itself worsened by increased abdominal weight—weight gain also makes controlling pressure, cholesterol, triglycerides and gout more difficult.

The patient that receives a prescription for two shots of NPH insulin a day will gain 10 pounds in a year. The patient that uses glyburide plus a single shot of NPH gains 9 pounds. The regimen combining  glyburide, metformin and a single shot of NPH, produces a similar weight gain. Metformin added to a single injection of NPH at bedtime produces no weight gain, the best control of the blood sugar and the least number of hypoglycemic attacks. The doctor with the prescription pad is producing this result—not the patient. These are impressive weight changes and they make a big difference over time. I have treated 450 type 2 diabetics for nearly 10 years with a regimen based on metformin and a long-acting insulin injection with durable control in most patients.

The treatment of high blood pressure hides the same kind of traps. Until very recently beta blockers like propranolol (Inderal), metoprolol (Toprol) and atenolol (Tenormin) were recommended as first line therapies for the treatment of hypertension.  Many patients continue to be on these medications for the one purpose of treating high blood pressure. These medications have important metabolic effects:

• Propranolol increases triglycerides by 25%, decreases HDL by 10%, increases total cholesterol by 9% and increases insulin resistance by 33%
• Metoprolol increases triglycerides by 30%, decreases HDL by 7%, decreases total cholesterol by 1%, and increases insulin resistance by 21%

Tricor (fenofibrate) is prescribed to treat the lipid or cholesterol abnormalities that go with the metabolic syndrome decreases triglycerides by 29%, increases HDL by 11%, and decreases total cholesterol by 18%.  When we prescribe propranolol and fenofibrate simultaneously, we have simply cancelled the lipid effect of two drugs.

The prescription of propranolol makes it 28% more likely that the patient will develop diabetes. Choosing an ACE inhibitor makes it 33% less likely that a patient will develop diabetes. These are critical metabolic issues. There is a newer beta blocker carvedilol, with dramatically improved metabolic effects relative to the older drugs.

The point of all this is that treatment of these patients is very complex if it is done properly. 95% of type 2 diabetes care is provided by primary care doctors who are under tremendous pressure to see patients at the rate of 5-6 per hour. They are required to be experts in the whole massive knowledge base of medical practice We need focused clinics of the type described by the Institute of Medicine to treat metabolic syndrome patients. The providers in these clinics will need to be very expert in the coordinated, integrated management of metabolic syndrome patients and the resulting complications. Until that happens, we will continue to produce the same poor levels of risk factor control and pay a terrible price in lives, disability and treasure.

by Pat Salber, MD

A small story in the business section of USA Today is good news (I hope). It says eleven major food companies, including giants Coca-Cola, Pepsi, and McDonalds will announce changes in how they advertise their products to kids. The Council of Better Business Bureaus (CBBB), in an effort to respond to the epidemic of childhood obesity, has organized the Childrens Food and Beverage Advertising Initiative to get food companies to “pledge” to stop advertising unhealthy products to children. These voluntary measures are supposed to go into effect by the end of 2008.

Evidently each company is making its own pledge. McDonalds, the article notes, will only promote meals with “no more than 600 calories, no more than 35% of calories from fat, 10% of calories from saturated fat and 35% total sugar by weight.” Is that dinner they are talking about? Or a mid-afternoon snack. When it comes to healthy eating, the devil is always in the details.  Products in Kraft Foods' Sensible Solutions line, which has less fat and calories than their other foods, will be the only types of products advertised to kids.

Although, the USA article was pretty positive about the Initiative, it did close with a quote from Kelly Brownell, director of the Rudd Center for Food Policy and Obesity at Yale University. Brownell says that the food companies’ voluntary guidelines for advertising to kids “are a good move in the right direction, the risk is that it stops here.” We’ve all seen that happen before, right? It is the rare industry that voluntarily reigns in bad practices that are highly profitable.

Digging Deeper

This article motivated me to dig a bit deeper. According to a press release found on the CBBB’s website, the eleven companies* participating in its Childrens Food and Beverage Advertising Initiative, have

“pledged to focus essentially all of their advertising primarily directed to children under 12 on products meeting better-for-you standards or refrain from advertising to that age group.” (Better-for you, compared to what?? … the high sugar, high fat they were advertising to kids before?). Steven J Cole, President and CEO of the CBBB goes on to day, “These expansive commitments significantly exceed the Initiative’s baseline requirements.”

The Pledges

Here are some of the pledges:

McDonalds:

All advertising primarily directed to children under 12 will be for meals that meet “specified calorie, fat, saturated fat, and sugar limitations consistent with the Dietary Guidelines for Americans 2005 and other government standards. They will restrict their advertising to the “Advertised Meal” that must provide no more than 600 calories; and no more than 35% of calories from fat, 10% of calories from saturated fat, and 35% total sugar by weight

The “Advertised Meal” will either be a 4 piece Chicken McNuggets® Happy Meal with low fat white milk and apple dippers with low-fat caramel dip or a Hamburger Happy Meal with low fat white milk and apple dippers with low-fat caramel dip. Scroll down to Appendix A of the pledge to see the details of what’s actually in the “Advertised Meals”

Kraft Foods

Kraft has pledged to only advertise products to children that meet its Sensible Solution nutrition criteria. Cool Whip Lite, Honey Maid Bees, Oscar Mayer Fat Free Wieners, and Lunchables Pizza are some of Kraft’s Sensible Solution products.  (Want to see the rest?  Here's the link to Krafts' Sensible Solutions products.)

General Mills

General Mills will no longer advertise to children foods with more than 12 grams per serving. (Be careful with this one, serving sizes are usually a fraction of what actually gets poured into the bowl or put on the plate). They also pledge to advertise only Healthy Dietary Choices to children under 12.

In fact, according to information on the CBBB website, General Mills has partnered with Nickelodeon (scroll down to page 4 of the pledge) to bring the popular Nickelodeon characters SpongeBob SquarePants, Dora the Explorer and Diego to frozen and canned vegetables. The goal is to make eating vegetables fun for kids. Each package of frozen vegetables will also include stickers featuring the characters that parents can use to reward children for eating their vegetables.

Note, these are frozen and canned vegetables – not the fresh kind that you can get for a fraction of the cost in the veggie section of your local market. And, it is of interest, that the brands touted in the pledge are frozen beans and frozen broccoli with butter sauce!

Never good enough.

I could go on and on, but you are probably thinking. What a crab…nothing is ever good enough. Well, in the midst of an obesity epidemic that threatens the world’s children with early onset chronic diseases and a shortened lifespan, then, heck yeah, promoting frozen buttered broccoli instead of the fresh kind and “apple dippers with low-fat caramel dip” instead of real low fat, fresh apples is not really good enough.

Let’s keep on pushing and pushing until the industry really gets it right. But, we have to do more than blab about it. We have to buy better, cook better, eat better and, in this way, fundamentally change the market for food.

Big job? You bet? But it can be done. Just the fact that these eleven companies are now trying to figure out how to market healthier foods indicates that they will respond to consumer demand (and regulatory threats). When more and more of us choose to shop in the outer perimeters of supermarkets (where the fresh foods are) or in local farmers’ markets, you can bet that industry will be watching.

Pat Salber, MD

Pat Salber MD

There are lots of health reasons to lose weight:  chronic illness prevention (e.g., diabetes, high blood pressure), better fit into imaging machines (such as MRIs) and mental health (some heavy people get depressed about their weight).  An Associated Press story this week adds to the list --  it can be tough to get rescued if you are really obese.

A 500-pound man went tubing on the St. Croix River.  He was following his doctor’s instructions to become more active.  Things were going well until his inner tube hit a rock and deflated.  

At some point after that, the 39 year old developed chest pain and his friends called 911.  A paramedic arrived by helicopter and “stabilized” him, but he was too heavy for the helicopter to carry.  More than 50 ground rescuers headed his way, arriving about an hour after the 911 call.

The rescuers really ran into trouble once they reached him.  The river was shallow and the ground, rocky.  They tried to use an aluminum boat as a makeshift stretcher to carry the man, however he weighed so much they could not carry him more than a few feet before having to put the man and boat back on the ground.  What to do?

The rescuers lashed three canoes together and placed four boards across them.  The man got on and the rescuers dragged the contraption for hours, finally reaching an ambulance almost twelve hours after the initial 911 call.  Thank heavens he wasn’t having a heart attack!

He was admitted to the hospital overnight. And, released the next day.  His mom says, “He is really pretty healthy.” 

Thank heavens.  If he had something that needed immediate attention, he would have paid a high price.  

In need of an immediate rescue?  “Yet, another reason to lose weight.”

Brian Klepper 

California always seems to be ahead on things that matter. A CNN story this week highlights that state's terrific anti-obesity TV campaign. The ads have cute kids sweetly asking "Dad, could you buy me some diabetes?" and "Can I drink another cup of sugar?" The goal is to shock adults into appreciating that the cheap, tasty foods they shovel down their children's gullets will have real impact. In one of the CNN clips, Adam Sandler says the ads work so well that he and his little girl suddenly dropped their cheeseburgers. I passed along the link to folks in Florida's government, and asked, "Why aren't we doing something like this?"

It's a fair question, but as I tried to point out in my post the other day on food companies' lobbying influence, these ads, powerful as they are, are hardly a match for the food industry's virtually unlimited resources and unrestrained marketing power. A well-intentioned state agency may place a few high profile ads, but the food companies can run theirs unrelentingly and in many different media. They're all over kids’ TV programming, in children’s books, and at schools. They have product placements in the movies, and are on Internet gaming sites. It's difficult to go head-to-head and expect to win against such sophisticated techniques and on so many fronts.

We’re utterly losing the war on obesity. The disease and cost numbers make that abundantly clear. The other day, Bob Laszewski at The Health Care Policy and Marketplace Review reminded us of an important 2005 Emory University study on the topic. The team, led by prominent health services researcher Kenneth Thorpe PhD, analyzed the 20 medical conditions that accounted for most of the growth in health insurance spending between 1987 and 2002.

The conditions, in order of their influence, included:

1. Newborn and Maternity Care
2. Cancer
3. Pulmonary Conditions
4. Arthritis
5. Mental Disorders
6. Hyperlipidemia
7. Hypertension
8. Lupus
9. Back Problems
10. Upper Gasterintestinal
11. Diabetes
12. Kidney Problems
13. Infectious Disease
14. Heart Disease
15. Skin Disorders
16. Bronchitis
17. Endocrine Disorders
18. Other Gasterointestinal Diseases
19. Bone Disorders
20. Cerebrovascular Disease

During that 15-year period, the cost of treating obesity-related conditions rose tenfold, growing to two-thirds of our total health care spending. The number of people who became obese, the percentage of obese people with serious medical conditions, and the cost to treat each obese patient all skyrocketed.

The study’s authors had a simple summary statement:

"If insurers and employers are serious about reigning in health care spending, then obesity prevention should be at the top of their agenda."

There's no mystery here. Long term, the magnitude of the obesity crisis threatens our national health and economic welfare. The roots of obesity-related diseases and their costs lie in the marketing methods of the fast, prepared and junk food industries. Look for the source, and you’ll find the food industry's boardrooms and their DC lobbying offices.

California has taken the first step on this issue. We’ll soon see whether Washington takes it as seriously. On Wednesday, Dr. James Holsinger, the White House' Surgeon General nominee said that, if he gets the job, he will focus on childhood obesity. It’s one right issue for our time, but talk is cheap. The real question is what he or someone like him would be willing to do. If he carries the torch for nutrition guidelines and curbs on food company marketing, then he’ll stand with our children and America’s future. But if he refuses to actively confront how foods are sold or what the obesity data say, then he’ll be standing with the food companies and their lobbying dollars.

Brian Klepper is a health care analyst based in Atlantic Beach, Florida. You can reach him at bklepper@gmail.com.

I recently came across an article in the April 23 issue of the Archives of Internal Medicine (vol. 167, pp. 802-807; 2007) describing a newly-discovered connection between depression and diabetes type 2 in older adults. The study enrolled 4,681 non-diabetic men and women over age 65, and followed them for 10 years. The participants filled out every year a questionnaire to measure their depressive symptoms, and every 2-4 years had their blood pressure measured. After removing confounding factors that are well known to increase the incidence of diabetes, like increased body mass index, alcohol consumption, and smoking, they discovered that even a single report of high depressive symptoms is highly associated with increased risk of diabetes type 2. In fact, there was a 60% increased chance of developing diabetes after reporting one incidence of high depression; this is significant by any measure.

Is it a good study?

I think it is an excellent study. The study group was ‘clean’, namely all diabetics and pre-diabetics were excluded from participation in the study. It was longitudinal, following the 4,581 participants for 10 years. The numbers were large enough and the observation period long. Furthermore, the authors accounted for all the obvious confounding factors, like obesity, smoking status, alcohol consumption, and anti depressant use. What is most convincing is that there was a relationship between the score of depression and the likelihood of developing diabetes, what we call in experimental medicine a ‘dose/ response’ relationship. The highest score had the highest increase in risk (60%).

How could depression cause diabetes?

There could be several explanations for this observation, and the answer is not really known. But if we look at the hormonal changes that accompany depression, we may find a possible link to diabetes. Cortisol is a stress hormone that is elevated in depressive states. Cortisol also happens to inhibit the secretion of insulin from the beta cells in the pancreas. Lower blood insulin would in turn lead to higher blood sugar, a hallmark of diabetes.

Caveat emptor

As always, when I speculate I feel obliged to caution that what ‘makes sense’, in biology it ain’t necessarily so. Biology is so complex, and largely still unknown, that any attempt to ‘dry lab’ it is an exercise in futility. Still, using speculation to form a testable hypothesis is how science works. For instance, we could test the cortisol hypothesis by measuring its blood levels in patients reporting an episode of depression and see if there is a correlation between it and the onset of diabetes. Or an experiment could be devised in which any participant reporting a depressive episode would be immediately treated with anti depressive drugs. Would that reduce the risk of developing diabetes?

I am sure many of you have other suggestions to study the depression/diabetes relationship. Send in your suggestions; we promise to publish and critique them.

Dov Michaeli, MD, Ph.D.

Thanks heavens, the Farm Bill is finally getting the attention of the healthcare community. In case you can’t make the link here are some equations:

Cheap corn = cheap high fructose corn syrup = fat = diabesity.

Pesticides + chemical fertilizers = toxic soil and toxic water

I could go on and on, but you get the point.

Michael Pollan, journalist and author of the best-selling book, "The Omnivore’s Dilemma," summed it up nicely in his April 22, 2007  NY Times opinion piece, "You Are What You Grow":

“Compared with a bunch of carrots, a package of Twinkies, to take one iconic processed foodlike substance as an example, is a highly complicated, high-tech piece of manufacture, involving no fewer than 39 ingredients, many themselves elaborately manufactured, as well as the packaging and a hefty marketing budget. So how can the supermarket possibly sell a pair of these synthetic cream-filled pseudocakes for less than a bunch of roots? For the answer, you need look no farther than the farm bill. This resolutely unglamorous and head-hurtingly complicated piece of legislation, which comes around roughly every five years and is about to do so again, sets the rules for the American food system — indeed, to a consi