Endodoc

An Apology

I apologize for the long time interval since my last entry. My excuse is a good one- I was visiting my daughter, her husband and their children, twins (Evan and Sophie). In fact my son-in-law is my webmaster and he taught me how to do links which I will try to add to many of my entries. Their family is rather interesting, although maybe not so much in California, where they live. They are judicious vegetarians and the grandchildren do not seem to have suffered any for it. The children have never, to the best of my knowledge,
set foot in a McDonald’s restaurant.

The “News”

There have been an increasing number of news reports about the “alarming” epidemic of obesity in children. Hello- where have people been the last decade or so? Also, more and more celebrities are wanting to get into the act. For example, there is a report in the New York Times today that former President of the United States, Bill Clinton is “teaming up” with Rachael Ray of the Food Network to promote healthy eating for children. The article is written by Kim Severson (“Dining In” section, page D4). Apparently, the cooking duet episode will be televised tomorrow (recorded April 12, 2007). President Clinton was Ms. Ray’s surprise guest and they are to be “partners in the fight against childhood obesity.” According to the report, President Clinton is flagellating himself for his previously terrible eating habits that may have contributed to his heart disease and recent quadruple coronary artery bypass surgery. Ms. Ray intends to work with the Alliance for a Healthier Generation, an organization founded jointly by President Clinton’s foundation and the American Heart Association to combat diabetes and obesity. Ms Ray apparently intends to help by talking about “how fun healthy food is, period.” Good for her.

Will any of this help? I doubt it but who knows? It can’t hurt

More News: Are Any Swedish Children Overweight?

In yesterday’s New York Times, there was a short report that Swedish children, like children in most developed nations (I won’t define what “developed” means), are getting heavier. It’s really not a surprise but somewhat of a disappointment for me- the Scandinavians have been “out front” in promoting health education, including nutritional education and physical education for some time. The only solace I have is that the increased prevalence of obesity is only a fraction of what we have seen in the U.S.

Even More News: Treating Obesity with Drugs

Also, in yesterday’s New York Times Jane Brody wrote an excellent review of current drug therapies for obesity, entitled “Weight-Loss Drugs: Hoopla and Hype.” She discussed both over-the-counter medications/products and prescription drugs. Let me summarize: don’t believe the claims about the over-the-counter products and watch out for the side effects of prescription drugs, especially given their (?very) limited benefits. Nothing new here but I think she did a nice job in sifting through a great deal of data. Darn, we are still going to have to suffer with healthy eating (remember it’s mostly too many calories in and not enough burned up through activity).

Probably from all the excitement about the report yesterday in the journal Science explaining why little dogs are little and big dogs are big, I forgot to mention a couple of things in my posting about the report. First, do you know why pigmies are short? It could be that they have the IGF-1 suppressor gene just like the little dogs.  Actually, they don’t; in the pigmies, the “problem” (I suspect the pigmies don’t consider their short stature a problem, just the normal state of affairs) is failure to respond to the IGF-1/IGFBP3 complex- they just don’t generate whatever growth factors are normally stimulated by the IGF-1/IGF-1BP3.  Just another example of what I mentioned yesterday- in nature, generally whatever can go wrong will do so sometimes.  Of course, we should be thankful that most of the time, things work just fine.

One other thing- treating people (or dogs) with IGF-1. I forgot to mention that IGF-1 must be injected, it’s very expensive,  and it causes hypoglycemia (low blood glucose levels).  Thus, treatment with IGF-1 has medical and financial risks.  The reason it causes hypoglycemia is that the structure of IGF-1 is very similar to the precursor molecule to insulin, proinsulin.  Thus, the IGF-1 acts like insulin in some ways.  I think that’s pretty interesting.

There is an interesting piece in the New York Times today ( Friday April 6, 2007, page A13) entitled “Difference Between Mutts and Jeffs? A Gene,” written by Donald G. McNeil, Jr. Before I get to the article, I need to tell you something about how children grow. There are many genetic and environmental factors that influence rate of growth and ultimate adult stature (just like there are many genetic and environmental factors that contribute to body weight).

For the moment, let’s just focus on some known hormonal influences on growth. Hormones are substances, usually polypeptides or proteins, that send messages to cells telling them what to do. We know that a hormone called growth hormone-releasing hormone (GHRH) which is produced in the hypothalamus (part of the brain), stimulates the pituitary gland (also in the brain) to produce and secrete another hormone called growth hormone (GH). GH circulates bound to a protein called GH-binding protein GHBP. The GH/GHBP complex binds to the liver where it stimulates production and secretion of another hormone called insulin growth factor 1 (IGF-1). IGF-1 circulates in the blood bound to another protein, IGFBP-3. Finally, the IGF-1/IGFBP-3 complex binds to tissues throughout the body, particularly muscle and bone, to promote growth. Sounds complicated? I suppose, but it’s a pretty slick system. We now know that in complex systems just about everything that could go wrong will. That is true for the growth hormone system; abnormalities and genetic variations have been described for each of the steps leading to the final expression of growth hormone secretion which is growth.

Growth hormone deficiency is one of the known causes for poor linerar growth. There are many different reasons for growth hormone deficiency (e.g., an absent pituitary gland, a pituitary gland damaged by radiation for treatment of a brain tumor, a genetic defect in formation of IGF-1). Thus GH deficiency is really a term used to describe a large number of possible abnormalities in the hormonal chain from the brain GHRH to the binding of the IGF-1/IGFBP3 complex in the tissues targeted for growth.

Back to the news report

So, the news article published today summarizes a study published today in the journal Science. According to the news report, the study which was led by Elaine A. Ostrander from the National Human Genome Research Institute, analyzed more than 3000 purebreds from 143 breeds. The researchers found that virtually all small dog breeds had a tiny bit of DNA that suppressed the “insulin-like growth factor 1″ gene; this suppressor gene was not present in large dog breeds. From what we discussed above, you can predict exactly what such a suppressor gene would do to linear growth and why: growth is slowed in the small dog breeds because they can’t generate nearly as much IGF-1 as the large dog breeds. So, in effect, small dog breeds have growth hormone deficiency, partial or complete depending on the extent of the IGF-1 suppression.

What are the clinical implications?

In humans, IGF-1 has been synthesized through recombinant DNA techniques and is being used in certain clinical situations. I’m not certain, but I think IGF-1s are species-specific (as are pituitary growth hormones). If this is true one probably couldn’t make a juvenile Scottie dog into a Great Dane-sized Scottie dog adult by giving human IGF-I injections. But who’s going to stop some enterprising scientist from trying it or from making a variety of small dog IGF-1s? Of course, one could also argue that we should insert the suppressor DNA into the genome of lovable large dogs to make them small and lovable? Oh the possibilites are just endless? Isn’t genetics interesting?

Anyway, in future entries, I promise to come back to growth hormone and growth in children. This news report was just too interesting to ignore.

I was pleased to read today in the New York Times (Wednesday, April 4, 2007 page A10) that the Robert Wood Johnson Foundation plans to spend a great deal of money over the next 5 years to “reverse the increase in childhood obesity.” From the news report it is difficult to tell exactly what the foundation intends to do- the article says that the foundation “plans to invest in programs to improve access to healthy food, encourage the development of safe play spaces, increase research to enhance understanding of obesity and prod governments into adopting policies to address the problem, among other things.” That sounds like quite an ambitious set of initiatives.

I’m not sure what I think about the foundation’s plans. Certainly we are in the midst of an obesity epidemic and we actually understand quite a bit about it. It’s genetics, cheap food, inactivity, etc. The question is whether focusing on the children in the ways the foundation intends will improve things appreciably in the long run? I do not want to seem the skeptic but I do not believe that unless we can “get to” the parents, we are not very likely to be successful in the long run; I don’t think it’s an analogous situation to childhood immunizations. Remember, the childhood obesity epidemic just mirrors what we see in the adults (60% of adults in the U.S. are overweight). Will “working on” the children change the way their parents feed them at home and when they eat out? Will it change the way the parents promote physical activities in the home setting? Maybe? Will it have any impact on what and how much the adults feed themselves and how much physical activity they engage in? Maybe?

In my last posting (31 March 2007), I put together a healthy eating plan for a hypothetical 9 year old boy. At first glance, you may think that the list of do’s and don’ts are obvious and can’t possibly be all that it takes to effect substantial weight loss? You would be wrong, and I will try to explain why.

Why do children get overweight?

In earlier postings, I discussed the many reasons for the present obesity epidemic. Regardless of the specific mechanisms involved, most obesity boils down to too many calories in and too few expended. In most instances, the positive calorie balance is only 100-200 per day. What that means is that some combination of 100-200 calories per day not eaten or “burned up” means no excessive weight gain; add another 100 calories or so to the negative side and it results in weight loss- remember that a negative calorie balance of only 100 per day results in a weight loss of almost a pound (0.45 kilograms) each month. That may not seem like a big deal but it’s almost 12 pounds in a year.

Where can I “find” those 100-200 calories per day?

If you re-examine the eating plan for John, our hypothetical 9 year old boy with obesity (posting of 31 March 2007), you will find that most recommendations are designed to cut back on calories consumed or increase calories expended.  For most people, It doesn’t take much of a change in their eating and their activity routines to find those 100-200 calories.  For example, each sugar-containing soda is about 160 calories.  Each extra spoonful of whatever is 50-100 calories or more.  Each slice of bread is 60-120 calories.  Each bedtime snack is- you don’t even want to think about it!  Each 30 minute walk is 100-200 calories depending on intensity.

You get the picture.  It’s only a question of knowing the plan and working hard each day to follow it.