By Dov Michaeli MD, Ph.D

We all heard this refrain; drug addicts kicking the habit, only to go through a lifetime of a constant battle to stay clean.

Why is it so hard? Why is it getting progressively harder within days after quitting? Who is the “devil that made them do it”?

The received wisdom for many years was that the reward system in the brain, which is the seat of all manners of addiction, is driven exclusively by dopamine receptors. But frankly, this belief had some problems. Here is a big one: the dopamine system is geared to maintaining homeostasis, which is the property of a living organism to regulate its internal environment so as to maintain a stable, constant condition. For example, exposure of dopaminergic neurons to increased concentrations of cocaine results in increased effects inside the cells. To maintain a constant internal environment inside the cell, the neuron responds by reducing the number of dopamine receptors. However, when the drug effect wanes, the addict feels depressed, and to get the same “high” in the face of reduced density of receptors he’d have to take an even higher dose of the drug, which would, in turn, result in yet another lowering of receptor density on the cell membrane. This is the basis of addiction; progressively elevated doses of the stimulus needed to obtain the same effect. Dopaminergic neurons respond in the same fashion to cessation of the stimulus, only in the opposite direction – the density of receptors increases back to the normal level. If the dopamine neurons were the sole ones involved, then this should be the end of addiction syndrome. But we know that this is not true.

We know that recovered addicts have to constantly battle the urge to go back on the drug. The dopamine receptor system does not explain this behavior.

The neurobiological basis of faltering resistance

Marina Wolff wanted to see if the neurons bearing the glutamate receptor have something to do with the difficulties addicts encounter after withdrawing from the drug. So she and her colleagues examined the glutamate neurons in the nucleus accumbens, which is part of the reward system and is involved in motivation and learning. They trained rats to self-administer cocaine by poking their noses into a hole when given a cue. As expected, the rats’ cocaine-seeking beahvior was more pronounced 45 days after the cocaine supply was cut off than after the first day. Examining the rats’ nucleus accumbens, they found something totally unexpected. Compared with rats in early withdrawal, rats deprived of cocaine for 45 days had incredibly high levels of a glutamate receptor of an unusual composition (called GluR2-lacking AMPA receptors). This unusual receptor promotes an inordinately strong response to glutamate. Indeed, if the new glutamate receptors were blocked in rats 45 days after cocaine withdrawal, their response to drug cues was cut by almost 50%. The conclusion according to Marina Wolff is obvious: the neurons were making new receptors in response to withdrawal, which explains the increased response to cocaine cues.

The implications

The obvious implication is that this receptor should be a powerful target for drugs designed to help in withdrawal from drug addiction.

But did you notice that this craving after withdrawal and the increasing difficulty in resisting cues is also an affliction of serial dieters? Indeed, eating stimulates the reward system just like any recreational drug; and overeating has all the hallmarks of addictive behavior. So, the obvious next step is to examine the levels of this unusual glutamate receptor in animals trained to overeat. It may be the answer to the losing battles millions of people wage every day in a desparate attempt to avoid re-gaining the weight they had lost.

Lastly, one more thought. Until only very few years ago it was believed that complex behaviors could never be explained by “simple”chemistry. Books and articles were written about the uniqueness of the brain, as if it obeyed different laws of physics. Here we have a receptor of a known composition, whose level in the brain controls a complex behavioral pattern. Can the day be far when we would be speaking of all human behavior in molecular terms?

By Dov Michaeli MD, Ph.D

Ever wondered if loss of weight causes a reduction in the number of your fat cells? Wouldn’t it be wonderful if that was true? You go on a diet, you lose weight and a bunch of cells, and you’d never gain weight again. Except it ain’t true, as anybody who went on a diet knows; unless you stick with your diet forever you will gain back the weight you had lost. Why is that?

Your fat cell allowance

In theory,there are two ways you can increase your body fat: you can increase the number of fat cells in the body, and you can store more fat in each cell. The second way, increase of the fat content per cell, has been amply documented; the reason we have so much evidence for that mode of weight gain is that it is quite easy to document. All that needs to be done is take biopsies of adipose tissue before the and during the weight gain and measure the fat content. And if you want to really nail it: take an additional biopsy after a weight loss diet, and document the drop in lipid content.

But what about the number of fat cells? That’s much tougher to measure, for obvious reasons: you can’t do a total body fat cell count. Or can you?

In animal studies, this question can be addressed by labelling DNA nucleotides with radioactive isotopes such as ¹⁴C. Differentiated fat cells do not divide, and so radioisotopes, incorporated in their DNA in the last round of division before differentiation, remain there throughout the cells' life. The time of radiolabel incorporation, is therefore the 'birth date' of these cells. But the potential toxicity of radioisotopes means that such studies cannot be performed in humans.

Kirsty Spalding and her colleagues at the Karolinska Institute in Stockholm cleverly thought of the next-best option. Atmospheric levels of ¹⁴C have remained relatively constant for centuries, with the only major increase occurring between 1955 and 1963, when nuclear bombs were being tested above ground. A chain of reactions ensures that, at any given time, the radioisotope content of human DNA matches that of the atmosphere. The authors could thus follow fat-cell dynamics in individuals born around 1955–63.

Spalding et al studied the dynamics of fat-cell number in some 700 adults, both lean and obese, and combined their data with previous observations in children and adolescents.

As the results show, fat cells have a high turnover: new cells are continually being born to replace their dead predecessors. The average age of a fat cell seems to be about 10 years in both lean and obese individuals, and the number of fat cells as a proportion of all cells remains constant in each weight group. But the total number of new fat cells was higher in obese subjects, suggesting that they are replenishing an existing larger pool.

What’s the take home lesson for lean people? and for obese people?

Do the lean among us need to worry about our diet if we have fewer fat cells? Yes, we do: our fewer fat cells can still store large amounts of fat. Also, can obese people do anything about their weight? After all, they've already accumulated a large pool of fat cells in childhood and adolescence? Again, the answer is yes. Again, the answer is yes. They can still reduce the volume, if not the number, of their fat cells. But there is another tantalizing message here: researchers should uncover the mechanisms underlying fat-cell turnover. If they do, one could conceivably slow down the replenishment of fat cells that came to the end of their ten-year life span. End result: progressively lower fat cell mass. This is still not a panacea; as we know from studies of people who had undergone liposuction--they slowly regain their previous weight by storing more fat in the remainig cells.

Liposuction: it's futile, lady.

Oh well, pass the fois gras!

By Dov Michaeli MD, Ph.D

The April 14 online edition of the Proceedings of the National Academy of Sciences carried an intriguing article titled “ Endogenous steroids and financial risk taking on a London trading floor”. Both authors, J.M. Coates and J. Herbert are from the Dept. of Physiology, Development and Neuroscience at Cambridge University . But J.M.C. is also from the School of business at Cambridge , and his main research interests are summarized by him thusly: “ I have been sampling endogenous steroids from traders on a trading floor in the City to determine the role of both testosterone and cortisol in their decision making and in their performance. I compliment this field work with behavioral experiments set in the lab and in artificial asset markets”

Raging hormones and bubbles

The rationale for this field of research is both compelling and fascinating. As stated by J.M.C  “ the waves of irrational exuberance and pessimism that destabilize the financial markets ,may be driven by naturally produced steroid hormones. With receptors in almost every nucleated cell in the body, steroids such as testosterone and cortisol affect the moods we experience, the memories we store and recall, and the behavior we display in competitive and risk-taking situations”.

This is absolutely fascinating because for the first time we find a serious attempt to explain economic phenomena on the basis of human physiology.

What they found

The investigators took saliva samples from 17 male traders on a London stock trading floor twice daily over the course of eight days. They monitored the traders' levels of testosterone, the hormone most often associated with aggression and sexual behavior, and cortisol, the so-called stress hormone.

They tracked those levels against the amount of money that a trader made or lost, and against the variation in the market. What they found was that when the traders made more money, they had elevated levels of testosterone. When the markets were particularly variable, they had elevated levels of cortisol.

Aha, you might aver; how do you know what is cause and what is effect? Isn’t it just as possible that traders had their testosterone levels go up as a consequence of making money?

Good thought, but…

A further analysis showed that traders who started their days with elevated testosterone made more money than those who didn't. One trader went on a six-day winning streak, making twice as much money each day as the previous one. Over that period, his testosterone levels rose steadily, some 74 per cent! This guy must have been a raging bull by the end of the week. Just think of the rollicking weekend he must have had.

So should stock traders join the ranks of sports figures and take testosterone as a performance enhancer?

Not quite. There is a point of diminishing returns; too much testosterone leads to too much aggression and reckless decision making. In some it may even lead to criminal behavior.

Cortisol, anxiety and risk management

Cortisol is one of the stress hormones. It rises when stress levels are up, which is stating the obvious. But what is less apparent is its role in limiting risk. Let’s go back to the savannah for a minute. You spot a lion striding toward you. Being the testosterone macho that you are you’d be perfectly willing to take the beast on. One guy, Samson, actually did it and lived to tell the tale, so why can’t you? Fortunately, your eyes send the brain another message: don’t kid yourself, this is dangerous! The order goes out to the adrenal glands and a flood of cortisol is released into the circulation, raising your anxiety level and making you have some second thoughts: after all, this is a tale from the bible, and you know how believable those are; besides, this guy Samson- did anybody see him kill the lion? Maybe he was just using it as a line to get Delilah to do what Philistine girls do better than the Israelite ones do? So you hedge your bets and climb up the closest tree. In other words, cortisol made you manage your risks more rationally.

Indeed, when the markets stopped going in one direction and started fluctuating, as markets always do, cortisol levels went up and trading became more restrained.

Of course there is a downside to cortisol as well, especially when exposure to it is chronic.

The downside of cortisol

A few days ago we reported on a Kaiser Permanente study that showed increased risk of dementia in males over 40 who had an increased central obesity, or abdominal girth that is 35 inches in women and 40 inches in men. Even men with a normal BMI had a 2 fold increase in risk if their abdominal fat was excessive. Now, if you think that you are in great shape because your BMI is within the normal limits, and you proudly display your six-pack abs to anybody who would care to look, think again . Experts now think that subcutaneous fat -- the flabby variety under the skin in areas like the buttocks, legs and arms -- while unfashionable, is fairly benign. Researchers at the Washington University School of Medicine in St. Louis demonstrated that when they removed an average of 22 pounds of subcutaneous fat via liposuction from 15 overweight women, they found no change in the women's cholesterol levels, triglycerides, insulin sensitivity or other health risks. We are talking here about visceral fat, or fat that underlines your awsome abs, lining your intestines and other internal organs. This fat in excess can be deadly. It is associated with the diseases of metabolic syndrome, but also with gall bladder disease, sleep apnea, numerous cancers, and dementia. So even if you are not flabby (you cannot pinch your skin and subcutaneous fat), but your belly is sticking out – you probably have excess visceral fat.

A major factor in determining this deadly distribution of fat is cortisol. This is probably why people under chronic stress are more prone to all the diseases we just mentioned.

But wait, there is more. Cortisol also causes increased risk of arthritis. It also leads to shrinkage of the prefrontal cortex and hippocampus, brain regions associated with decision making and factual memory, meanwhile it contributes to growth in the amygdala, a region associated with emotional memory and anxiety. Not good stuff.

The good news

Cortisol levels can be controlled by reducing stress levels. And visceral fat is the first to go when someone loses weight in general. Aerobic exercise, like walking or running, is particularly effective. Doing sit-ups, abdominal crunches and pilates can strengthen your abdominal muscles, and help hold your stomach in, but they won't target visceral fat specifically.

Some final thoughts on stock trading

Here are some questions that beg for a study.

· Are women better traders because they are less prone to wild speculation?

· Are stock traders more prone to heart disease and diabetes? Or more critically for their clients, are they likelier to become demented?

· Should clients insist on a broker’s full disclosure of his health record?

Or may be the answer is a lot simpler: get a woman broker.

By Dov Michaeli MD, Ph.D

It almost became a cliché: losing weight is relatively easy. That’s why you see so many “miracle diet” claiming astounding losses of weight. But why don’t we see miracle diets that tout maintenance of weight loss? Because this is the hard part of dieting. The reasons for that are both psychological and physiological, and the neurobiology of it is fascinating.

The neurobiology of diet failure

If you imagine the brain as made up of layers, the deeper ones are made of neurons that determine our response to environmental stimuli without us being conscious of it. If we come across an environmental cue that stimulates our feeding response, like a delicious looking chocolate cake, the response is an outpouring of hormones and peptides that signal to the brain: I’ve got to have that! Now, all this happens at speeds that are measured in milliseconds and microseconds—an astounding speed that eludes our consciousness. By the time our conscious thoughts take over, it is almost too late. These conscious thoughts travel in the cortex, the outer layer of the brain, at far slower speeds, measured in seconds. So by the time we try to exert some judgment (“I really shouldn’t”) the mood for the decision-making has already been formed. To counteract it is tough, and the longer we allow the “unconscious” pathways to prevail —the stronger the neuronal circuits that determine the response become. This is why it is so difficult to kick the habit, any habit, including overeating.

How can we win the battle of the brain?

The deeper, more primitive and fast moving neuronal circuits, can be restrained. By using the conscious, slow moving circuits again and again, over long periods of time, they become “unconscious”, and a lot more effective in intercepting our initial “bad” instincts. How this happens is a bit complicated and not completely known. But basically, they bypass the prefrontal cortex, the “decider” center in the brain. That is time-saving. Just imagine if every time we wanted to tie our shoe laces we had to recapitulate consciously the steps that we learned (consciously) in childhood. Repetition made it “unconscious”, and fast. Same for the multiplication table, for reading, for any learned activity that we repeat many times.

What does it have to do with weight maintenance?

A lot. If we could educate our conscious neurons to automatically resist that enticing chocolate cake, they would become “subconscious” and more effective in resisting the initial temptation. Yes, it requires repetition. And every iteration is a battle that has to be fought and won. I can understand St. Augustine ,  a 3^rd century bon vivant pagan who converted to Christianity, and who plaintively exclaimed: “Oh Lord, lead me not into temptation…but not quite yet”. The poor saint had to exile himself to the Syrian desert to deprive himself from the tempting “cues”of Rome. Even that fell short, and those “cues” came visiting and haunting. He could purge those unholy thoughts by flagellating himself—which is an extreme way of educating the subconscious. But it worked, and he could consequently devote himself to something more acceptable (to him): translating the Bible into Latin. And this brings up another aspect of “educating” the brain: the strength of the “educating” signal is as important as repetition.

But I am digressing. The “cue” that launched me into a journey of the brain was an article in the March issue of JAMA, titled “Comparison of Strategies for Sustaining Weight Loss”. This was a two-phase trial in which 1032 overweight or obese adults (38% African American, 63% women) with hypertension, dyslipidemia, or both who had lost at least 4 kg (9.2 lbs) during a 6-month weight loss program (phase 1) were randomized to a weight-loss maintenance intervention (phase 2). After the phase 1 weight-loss program, participants were randomized to one of the following groups for 30 months: monthly personal contact, unlimited access to an interactive technology–based intervention, or self-directed control.

The results: after 30 months , participants receiving personal counseling retained an average weight loss of 9.2 pounds, compared to an average of 7.3 pounds for those using the Web-based intervention and 6.4 pounds for those in the self-directed group.

After reading this blog we could have predicted this outcome. The personal counseling group received a stronger signal than the web-based group, and both received stronger “education” than the self-directed group.

You might think that a difference of 1.8 pounds between the two treatment groups may not justify the cost of personal counseling. Then think again: Each 2.2 pounds of weight loss can lower blood pressure by one point and can lower the risk of developing diabetes by 16 percent in high-risk adults . This is quite a reduction in health care costs.

 Is anybody  in Washington  listening?

By Dov Michaeli MD, Ph.D

Every Sunday morning we have a family ritual: 8-9 in the morning it’s “Meet the Press”, 9-9:30—the Chris Matthews Show. And while the TV is blaring and we OD on politics, we walk on the treadmill or step on the elliptical, do abdominals and pushups, do Yoga and lift weights—in short: we indulge our political and fitness addictions simultaneously, and feel self-righteous and quite superior to the flabby unwashed masses.

I love to watch Chris at his best: benignly opinionated, urging his guests to express their opinion on a political subject before pronouncing the Matthews ‘truth’ (“Tell me something I don’t know… here is what I think”), full of lively energy; the man is manifestly enjoying exposing hypocrisy, mendacity, stupidity and other ills of our political leading lights.

So guess how surprised I was when I found out that Chris Matthews makes stupid mistakes, like any one of us. As I sorted through today’s mail my eyes fell on the cover of the latest issue of Diabetes Forecast. There he is on the cover, smiling his heart-melting Irish smile, over the title: “Chris Matthews: the Hardball host goes head-to-head with type 2”. I guess for the readership of this magazine there is only one sort of “type 2”— diabetes. Chris was interviewed by Dan Gilgoff, the politics editor of Beliefnet.com and author of The Jesus Machine: How James Dobson, Focus on the Family, and Evangelical America are Winning the Culture War. (I can’t resist a digression here. Dan, don’t fret: Dobson, Focus on the Family, and Evangelical America are losing the cultural war!).

The interview was an eye-opener for me. I have to admit, I used to attribute much of the American people’s lack of sophistication in health matters to poor education. No more; here is a highly educated individual, possessing an uncanny capacity to ferret out ignorance, stupidity, and dishonesty who betrays an incredible degree of ignorance when it comes to his own health.

Here are some excerpts from the interview, along with some gratutitous comments.

Q. You knew for years that you had diabetes but did very little about it.

A. … I had malaria after coming back from a trip to South Africa in 2001, but what I kept [hearing about] from my doctor was my high blood sugar levels. And I said, “What does that have to do with anything?”

Comment: Chris, with your sharp ear to nuance and encrypted messages—what did you think your doctor was trying to tell you? And you, doctor, were you too pressed for time to press your point home? By the way, going to South Africa without taking the Malaria pills? Did you think you were beyond the reach of lowly creatures such as mosquitoes?

Q. But you more or less ignored your diabetes until even more recently, right?

A… I also wasn’t doing any kind of dieting. I was aware of a general need to skip some things. The toughest habit is going to an airport in the morning when you haven’t had breakfast and seeing the pastries there. Hunger is the best chef—you see a couple pastries and have that and a cup of coffee for breakfast. There was a time when I’d have a hamburger and French fries for lunch with a beer or white wine, and I’d have cheesecake for dessert. It was pretty outrageous.

Comment: I agree. Many a time did I find myself struggling to walk past the Peet’s and Starbuck’s Coffee stands at the SF airport, without succumbing to the temptation of the pastries. But where was your doctor? How come you weren’t warned about pastries, hamburgers, French fries, beer or white wine for lunch? This is inexcusable.

Q. Did you consider reforming your diet after learning about your high blood sugar levels?

A…. I didn’t say, “Wait a minute, this is something I can reasonably deal with.” I didn’t understand the importance of it or the doability of it—that I could solve this problem, that it would be over, and I would be just like everybody else….

Comment: That he didn’t understand the importance of it is in part his doctor’s fault, and in part Matthews’ own dismissive attitude when confronted with inconvenient facts.

Q. You stayed in the hospital a few days. How scary was it?

A. When you have three doses of morphine and it still hurts, you begin to worry.

Comment: And I am sure you went back to your TV show, blasting any and all comers for their lack of clear solutions to our health care problem. Chris, it is people like you who are part of the problem.

Q. You’ve certainly lost a good bit of weight in the past year.

A. On my scale at home I’ve gone from around 235 to about 205, and I think I can lose some more if I do a little more exercise. I really haven’t done any exercise to lose all this weight, just changing what I eat.

Comment: Chris, I watch you every Sunday on TV. You need to lose a minimum of 20 more lbs. You may rid yourself of the daily insulin injections, and as a bonus, you’ll wow the beautiful female political commentators on your show if you lost 40 lbs, and exercised!

Q. Why your aversion to exercise?

A. Don’t have any time. When am I going to do it?

Comment: What a lame excuse. There are people who run multi-billion dollar enterprises who find time to exercise. You make time, Chris. Get up one hour before you normally do, and just do it. It is going to grow on you, it will energize you to go after the bad guys, and you’ll feel sick on days that you skip—I guarantee it.

Q. As a public figure, do you feel obligated to send a message about diabetes?

A. What people ought to be told about diabetes is that if they have it in the family or sense that they’re on the road to it, they should go to their doctor and ask him what he thinks and actually listen to the doctor like they would use [their] financial advisor.

Maybe it’s an Irish thing—we like to think we can talk our way out of things or that we can avoid them. But I’ve come to respect doctors a whole lot through this whole thing because they know what they’re talking about and they’re telling you to do something for your own good.

Comment: You are right, Chris; people ought to listen, even more than to their financial advisor. It is a matter of their health and life—pretty existential stuff.

But you are wrong about it being an “Irish thing”. I have had Russian patients come in with a list of medications and treatments they had decided they needed, and all attempts at telling them otherwise were a waste of time. My own father would go to the doctor only to tear up the prescriptions he was given and treat himself with his grandmother’s nostrums. And my Rabbi told me that when your Celtic forefathers had no idea that the emerald island even existed, the Jews of Ireland already suffered from diabetes. And why did they have diabetes? Because they didn’t listen to their (Jewish) doctors.

See you next Sunday on TV.

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

By Dov Michaeli MD, Ph.D

Some of the health advice we come across in the media and the internet is so outrageous it borders on quackery; no, it is quackery. If it wasn’t so dangerous it would be hilarious. So I thought we should all share in the hilarity. But before we proceed, a disclaimer: the following is based on actual Q and A, but the author took  literary license to highlight their innaneness (there, I finally got to use this word). So here goes:

HEALTH QUESTION & ANSWER SESSION
Q: I've heard that cardiovascular exercise can prolong life; is this true?
A: Your heart is only good for so many beats, and that's it... don't waste them on exercise. Everything wears out eventually. Speeding up your heart will not make you live longer; that's like saying you can extend the life of your car by driving it faster. Want to live longer? Take a nap.

Q: Should I cut down on meat and eat more fruits and vegetables?
A: You must grasp logistical efficiencies. What does a cow eat? Hay and corn. And what are these? Vegetables. So a steak is nothing more than an efficient mechanism of delivering vegetables to your system. Need grain? Eat chicken. Beef is also a good source of field grass (green leafy vegetable). And a pork chop can give you 100% of your recommended daily allowance of vegetable products.

Q: Should I reduce my alcohol intake?
A: No, not at all. Wine is made from fruit. Brandy is distilled wine, that means they take the water out of the fruity bit so you get even more of the goodness that way. Beer is also made out of grain. Bottoms up!

Q: How can I calculate my body/fat ratio?
A: Well, if you have a body and you have fat, your ratio is one to one. If you have two bodies, your ratio is two to one, etc.

Q: What are some of the advantages of participating in a regular exercise program?
A: Can't think of a single one, sorry. My philosophy is: No Pain...Good!

Q: Aren't fried foods bad for you?
A: YOU'RE NOT LISTENING!!! ... Foods are fried these days in vegetable oil. In fact, they're permeated in it. How could getting more vegetables be bad for you?

Q: Will sit-ups help prevent me from getting a little soft around the middle?
A: Definitely not! When you exercise a muscle, it gets bigger. You should only be doing sit-ups if you want a bigger stomach.

Q: Is chocolate bad for me?
A: Are you crazy? HELLO . Cocoa beans! Another vegetable!!! It's the best feel-good food around!

Q: Is swimming good for your figure?
A: If swimming is good for your figure, explain whales to me.


Q: Is getting in-shape important for my lifestyle?
A: Hey! 'Round' is a shape!


Well, I hope this has cleared up any misconceptions you may have had about food and diets.

Finally, an exercise regimen I found in a Man's Health magazine. I have been following it religiously:

You have to give this a try, it really works.

This exercise is suggested for mature adults, to build muscle strength in the arms and shoulders. It seems so easy, so I thought I'd pass it on. I suggest doing it three days a week.
Begin by standing on a comfortable surface, where you have plenty of room at each side. With a 5-lb potato sack in each hand, extend your arms straight out from your sides and hold them there as long as you can.

Try to reach a full minute, and then relax.

Each day, you'll find that you can hold this position for just a bit longer. After a couple of weeks, move up to 10-lb potato sacks. Then try 50-lb potato sacks and then eventually try to get to where you can lift a 100-lb potato sack in each hand and hold your arms straight for more than a full minute. (I'm at this level)

After you feel confident at that level, put a potato in each of the sacks.

And remember:

"Life should NOT be a journey to the grave with the intention of arriving safely in an attractive and well preserved body, but rather to skid in sideways - beer in one hand - chocolate in the other - body thoroughly used up, totally worn out and screaming "WOO HOO, What a Ride"

Dov Michaeli MD, Ph.D is in the biotech industry and is a nut when it comes to diet and exercise.

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.

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.

Brian Klepper 

How do you live a long life? Take a two-mile walk every morning before breakfast.

Harry Truman
33rd US President, who lived to 88

DAWN, n. The time when men of reason go to bed. Certain old men prefer to rise at about that time, taking a cold bath and a long walk with an empty stomach, and otherwise mortifying the flesh. They then point with pride to these practices as the cause of their sturdy health and ripe years, the truth being that they are hearty and old, not because of their habits, but in spite of them. The reason we find only robust persons doing this thing is that it has killed all the others who have tried it.

Ambrose Bierce, The Devil's Dictionary 

I started taking long walks with my close friend Bob thirty-five years ago when we were students in Holland. We would walk and discuss the things that young people ponder, passing time in the brisk beautiful outdoor landscape of Northern Europe. We always maintained a quick pace, but never minded the effort, because the activity was filled with ideas and always-inviting scenery.

When I returned home, walking was a habit that stuck with me. When Bob and I lived in the same town, we'd get together regularly to walk the dogs. On my own, I found that I could go out for a stroll and think, chewing on whatever I was working on and, getting a little distance from it, find perspective. Elaine and I still walk, constantly, and that's where we get some of our best talking in. Walking has been respite from the rush, a place to hash out conflicts or work out plans, a way to meditate and regain balance.

When I left my post at the University of Florida about 20 years ago and returned home, I traded a landlocked town for the coast. As quickly as I could, I resettled within a few blocks of the beach in a small community on an island off Jacksonville, in Northeast Florida. Then, as now, I was literally within a five minute walk of a 300 foot wide, hard-packed, sugary white sand beach on the Atlantic, stretching for miles both north and south. In addition to the spectacular, always changing beauty of a vibrant seascape - birds, dolphins, turtle nests, fish and other sealife; the boats and ships just offshore; the surf rolling in and lapping the beach - it was perfect terrain for a habitual walker.

Even so, as easily accessible as it is, and though I know lots of people long for just this sort of environment, there have been periods when I lost my discipline, when I took the opportunity for granted and somehow just didn't get around to it.

Then came the moment 5 years ago when I unexpectedly had open heart surgery, a 5 vessel CABG, the result of lousy genes and the gradual relentless buildup of plaque choking off my blood vessels. During the procedure they collapsed and then re-inflated my lungs, and I knew it would take work to ameliorate my shortness of breath. I started walking again immediately, through the halls, on the second day in the hospital following my surgery, and by the time I left 3 days later I was up to walking more than a mile a day.

I continued when I returned home and worked through recovery, and though increasing my distance went slowly, I kept at it. During a follow-up with my surgeon, he commented, "The best thing you can become is a walking fool. It's low impact, steady and its good for you in all kinds of ways, especially with what you're up against."

And then, again, time passed and I got comfortable and distracted. I skipped my walks and then they trickled away, until I was just walking weekends again. I told myself that I was really in OK shape, but the truth was that I put on weight and that I had slipped into a malaise.

Recently, I had a discussion with a good friend, a preventive cardiologist, who gave it to me straight. I had shared the numbers from my last blood panel. "Look," he said, "you're not taking this seriously. Unless you get your LDLs (the bad cholesterol) down below 60,  you're going to continue laying down plaque, and the risk increases. If you're interested in doing what you can do, you need to get religion on this. Get lean. Eat carefully and ramp up your exercise."

And so I have.

This isn't just theory. Below is a picture from the REVERSAL Trial, led by Steven Nissen MD, chief of Cardiology at Cleveland Clinic. It clearly shows the before and after effects of managing LDL to below 60. After 18 months of the reduced LDLs, there's been a significant opening of the vessel. This is what I'm shooting for.

So we've cut out most breads and sweets. Cookies are out. Our diet is mostly fruits, veggies and fish. Once you get your head around it, it makes sense and you gradually lose the longing for the comfort foods: a milk shake, macaroni and cheese, or a fried fish sandwich.

And then there's the walking. It's a flat 3 miles, 50 minutes door-to-door, down to the lifeguard station on the beach and back, walking fast. Right now, in the NE Florida swelter, I'm soaked through when I return. I do this twice a day. On my suburban beach, around 6AM, there are 200 people out there walking before work. After work, you see  a lot of them again.

 An embarrassing quantity of pounds has melted off. I'm becoming leaner and stronger than I've been in years. The next blood panel will tell. When I'm tempted by some forbidden food, I think of 60 and my will to shrink the plaque that's strangling my vessels.

And I walk.

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

Alli (pronounced "ally") was approved by the FDA in February and will hit the shelves tomorrow.  About half of people in clinical trial studies were able to lose approximately 5% of their body weight in six months.  The medication is supposed to be taken three times a day and will cost about $50 per month. 

Sounds good?  Yeah, but the devil is in the details -- or, in this case, in the side effects.  

This "fat-buster" may not become a blockbuster for its manufacturer, GlaxoSmithKline.  Here's why from an "oldie, but goodie" TDWI post from February 7, 2007:

If you can deal with the "icky" factor, Alli may help you lose weight

Pat Salber, MD

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Is "Accomplia" the next silver bullet in weight control?     (Note:  On February 13, 2007, a U.S. Food and Drug Administration panel Wednesday unanimously rejected Acomplia, a weight-loss drug from Sanofi-Aventis  on concerns the drug increases the number of psychiatric events like depression and suicidal thinking among users.

The results of the 2007  Food and Health Survey* are in and they show…guess what? Most people want to lose weight. Seventy-five percent of individuals surveyed said they are concerned with their weight. This is up from 66% in 2006. 70% said their reason for making dietary changes is “to lose weight,” and 56% said they are actively trying to lose weight. This is interesting as it seems to reflect reality.  According to the latest scientific evidence, 66% of Americans are overweight or obese.

Where there is a disconnect, however, is people’s knowledge of the relationship between "calories in" and "fat on."  Although 60% of Americans who are trying to lose weight say they are doing so by reducing the number of calories they consume, only 11 percent were able to correctly estimate the number of calories they should consume in order to accomplish that goal. Interestingly, most people underestimated the number of calories they thought they should consume, but that was offset by the 34% of Americans who admitted they actually consume more than they estimated they needed.

It was heartening to learn that most people (69%) say they use food and beverage packaging elements when deciding whether or not to buy and eat food products. However, the most commonly used element was the expiration date. Sixty-six percent said they used the Nutrition Facts Panel (aka the Nutrition Label) and most used the calorie information and the information about fats, particularly Trans fats. The problem is they are not paying attention to serving size – only 49% did so, down from 63% in 2006. Knowing the calories per serving does not translate into decreased caloric consumption if you do not understand serving size.  And, as I have pointed out before, serving size is not intuitive or even easy to understand (how many of us can estimate 1 oz of cashews or 30 grams of Bran Buds?).

Of the 56% of people surveyed who said they were trying to lose weight, 79% said they had increased or began to engage in physical activity; 69% had reduced portion sizes of meals and/or snacks, and 60% had reduced the number of calories. But snacking remains a national pastime with about half of those surveyed saying snacks are an important part of an overall healthful diet. Almost all Americans (93%) eat at least one snack per day with the mean number of snacks being 2.5 per day. Ten percent of those surveyed said they ate 4-5 snacks per day and 7% ate 6-7 per day. Two percent admitted to eating 8 or more snacks per day (how do they have time for anything else??).

Many people perceived foods and beverages to have health benefits, often beyond what medical evidence supports. Specifically, the following percentages of the surveyed population strongly or somewhat agree with the following statements:

• Specific foods improve heart health – 80%
• Specific foods improve physical energy or stamina – 76%
• Specific foods improve immune system function – 71%
• Specific foods improve mental performance – 66%
• Specific foods improve the risk of getting specific diseases – 65%

Can’t you just see the glint in the food manufacturers’ eyes (and the banners proclaiming health benefits plastered all over our food packages)? Food lies masquerading as food science – but, you will have to wait for that is the subject of a post yet to come.

The last item from this survey that I want to mention is that American’s perceived their health to be better in 2007 than in 2006. Thirty-nine percent of those surveyed said their health was “excellent” or “very good” compared to only 33% in 2006. And even more people (58%) said they were “extremely satisfied” or “somewhat satisfied” with their health status – this is somewhat puzzling since that means some people are satisfied with health that is less than “very good.”

So there you have it – a glimpse into how we perceive food, fat, and facts.

*The Survey, sponsored by the International Food Information Council (IFIC) Foundation and organization affiliated and supported by “the broad-based food, beverage, and agricultural industries.” The first survey was produced in 2006 based on a telephone survey of Americans performed in November 2006. The 2007 Survey is based on a telephone survey in March of 07.

Pat Salber, MD

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Yesterday’s New York Times ( May 8, 2007 ) carried a front page article by one of the paper’s premier science reporters, Gina Kolata. The article, titled “genes take charge, and diets fall by the wayside”, is an excerpt of her newly published book “Rethinking thin: the new science of weight loss- and the myths and realities of weight loss”. In the article she reviews the succession of studies started in the late 1950’s by Dr Jules Hirsch at Rockefeller University , which culminated in recent studies demonstrating conclusively that the tendency to weight gain and obesity is genetically determined. Ms. Kolata describes the heartbreak of dieting, a constant struggle of losing weight, trying to maintain, gaining, dieting again, and so on and so on. Psychological testing showed the toll this struggle can take; people are perpetually unhappy, many are chronically depressed, some are suicidal.

One of the major conclusions Kolata cites is that each body has a metabolic “comfort zone”, and dieting to go below this zone is painful, metabolically unsound, and essentially futile.

I admit I haven’t read the book yet, but if the excerpt reflects the message of the book, I strongly disagree.

Why?

For several reasons:

· Yes, a metabolic range specific to each body makes a lot of intuitive sense. But to accept it we need to see the genetic/molecular/physiological mechanisms. The evidence is still not in. Having been around the block a few times, I never cease to marvel at nature outsmarting us, and upending our ‘no brainers’ and ‘slam dunks’.

· The fact that genes control our metabolism does not mean that they are the sole players. Genes interact with the environment, and the outcome of this interaction is all important. The old debate of nature vs. nurture set up a false choice; nature and nurture operate together in biology. The best example is diabetes type 2. An individual may have the genes that predispose to this disease. But it will be expressed clinically only if that individual overeats and exceeds a certain BMI.

· The most obvious evidence that genes are not the final word in weight regulation is the recent obesity epidemic. If  "obesity genes",which undoubtedly have been with us for eons, were such an all-controlling factor, why is it that only in the last few years did this epidemic break out? The answer is well-known: we take in a lot more calories, and we exercise a lot less. Yes, the genes were there all along, but they were not expressed.

I believe that research into the genetic basis of obesity and diabetes is absolutely essential. But it should not become an excuse for the fatalistic attitude of “it’s beyond my control”. Counteracting and ovecoming the genetic dictate may be unpleasant, tough, exasperating—but it beats the alternative.

Dov Michaeli MD, Ph.D