Endodoc

I tried really hard to ignore the front page article in the New York Times on Wednesday, January 23, 2008, entitled “Diabetes Study Favors Surgery to Treat Obese,” and written by Denise Grady. And, I was doing well until this morning (Sunday, January 27, 2008) despite e-mails this week from patients of mine wondering if they should get gastric banding surgery, when I saw the following headline in the Columbia Daily Tribune: “Diabetes Cure Linked To Surgery”. I now feel an intense need to respond.

Background

Those of you have read my earlier postings about obesity and the links with type 2 diabetes already know that for most people, getting type 2 diabetes takes both obesity and the genes for type 2 diabetes- it’s opportunity and genetics at their best (or worst). Type 2 diabetes is, for most people a combination of insulin deficiency and insulin resistance. Obesity causes insulin resistance and this is often enough to “tip the balance” leading to expression of the diabetes, i.e., high blood sugar levels. We have known for many, many years that early in the course of type 2 diabetes, losing weight, no matter how it is done, often leads to remission of the diabetes, which may persist long-term, but only if the weight is not regained. We even know from an excellent study called the Diabetes Prevention Trial (or “DPP” as it is widlely known) that treating obese people who have mildly abnormal blood sugar levels with diet and exercise that leads to weight loss, can greatly decrease the rate at which such people develop full-blown diabetes. Are you with me so far?

Bariatric Surgery For Obesity/Diabetes

As I discussed in earlier postings, bariatric surgery (bariatric is from the Greek work “baros,” meaning weight) is a well-accepted approach to treating severe forms of obesity that are unresponsive to medical therapies (e.g, diet, exercise). Despite the high costs and complications, for people with severe obesity, the complications of the obesity often make the surgery worthwhile. There are a number of studies worldwide that document the long-term benefits from bariatric surgery in selected patients. So now we have a report published in the Journal of the American Medical Association (JAMA) on January 23, 2008 suggesting that bariatric surgery might be the way to go in curing type 2 diabetes in its early stages.

What Did The Article Show?

The study was performed by a research team at Monash University in Melbourne, Australia. The lead author was John Dixon. Dr. Dixon and colleagues studied 60 patients with recently-diagnosed type 2 diabetes who were obese (BMIs 30-40). The investigators randomly assigned patients to either bariatric surgery (with a gastric banding procedure) or traditional treatment for the diabetes (diet, exercise, medications, etc.). They found that after 2 years, the surgery group had complete remission of the diabetes in 73% vs. only 13% in the non-surgery treatment group. The authors concluded that bariatric surgery was an effective alternative to the usual approach to treating type 2 diabetes. The authors predicted that bariatric surgery would be used more and more in the future to treat diabetes.

Is This News Or No News?

There is a National Public Radio show called “Wait, Wait Don’t Tell Me,” which is basically a quiz show on current events. In one segment of the show the host asks the guest panel members to decide if a piece of recent news is, in fact news or no news (i.e., a big deal or nothing exciting). So, let’s pretend I am on that guest panel and the host asks if the bariatric surgery study summarized above is news or no news. What would I say? I would say “no news.” Why? First, I would point out that the surgery, not surprisingly, was associated with striking weight loss compared to the non-surgery group. No duh. I would also point out that the study was very short-term- two years total, far to short to really assess the long-term benefit of a surgical procedure that costs $15,000-$25,000 in the U.S. For example, in 10 years, how many of the surgical group patients have diabetes compared to the non-surgical group patients? How many of the surgical patients had developed complications from their surgeries? You get my drift? This small, short-term study should not be used as the basis for moving to bariatric surgery as the method of choice for treating diabetes in people with mild degrees of obesity (BMIs 30-35%, like a large percentage of those in the U.S. who do not have diabetes (at least not yet). Maybe someday we will need to accept the fact that surgery is the best way to treat all obesity, with or without diabetes. We are a long way from that someday.
The New York Times article was well written and explored the various issues I have raised. The article in my local newspaper was scary. The subject of the article was a local bariatric surgeon who is clearly hoping to greatly increase the number of bariatric surgery procedures he performs in people with type 2 diabetes. I would suggest that he go slow and curb his enthusiasm until we have much more data. Of course, he may find that many insurers, including Medicare, will not jump at the chance to help out the rapidly growing number of bariatric surgeons in the U.S.

A Plea

This is as much about obesity as it is about diabetes. I hope we have not given up on the possibility of controlling our national passions for food and inactivity through means other than surgery. I like surgeons and some of them are close friends of mine but I do not like the idea of surrendering the management of obesity/diabetes to the scalpel just yet.

Did that title catch your eye? I hope so. Before explaining about the title I want to urge you, my readers to feel free to comment on my entries. I do know that many people from all around the globe read my entries but I rarely receive comments or questions. Even criticisms (mild ones) would be welcome. I also welcome suggestions for future topics.

Now, about the title. My daughter’s daughter (that makes her child my granddaughter) just happens to have celiac disease. My daughter called me to complain that in my last entry (a case about celiac disease), I did not emphasize how important it is to have universal screening for celiac disease. I told her that whether or not to screen for this or that disease is not so simple. It is getting even more complicated daily, as new genetic tests are springing up. For example, is it worth knowing if a guy has an increased risk of developing prostate cancer? That was the question posed on the front page of the New York Times today (Thursday, January 17, 2008). The article was entitled “$300 to Learn Risk of Cancer of the Prostate,” and written by Gina Kolata. In summary, a new study to be published in the New England Journal of Medicine on January 31, 2008 (the study was published on-line on January16, 2008), shows that a new genetic test can identify men who have a particularly high risk of developing prostate cancer. The scientists identified 5 regions in DNA in which variants in the DNA were associated with increased prostate cancer risks- the greater the number of variants, the greater the risk- up to 4.5 fold with 4 or 5 variants (out of 5 possible). With a family history of prostate cancer, the risk in these “high-variant” subjects jumped to about 10-fold. Anyway, the author did a good job in addressing just how complicated it is in deciding who and when to screen for diseases. In this instance, and in a rapidly increasing number of instances, some of the same scientists who discovered the genes are involved in marketing a genetic test to determine risk. This makes it difficult to determine if their recommendations for screening are based solely on sound medical principles, or might be influenced a bit by the profit motive?

Screening for a disorder is generally defined as testing asymptomatic people for a disease or increased risk for a disease. Whether or not to screen for a disorder depends on many factors including costs. For example, if it costs millions of dollars to identify one case of this or that, is it worth it? It also depends on whether the outcome is any different with earlier diagnosis . It also matters whether the screening is to determine if someone has an increased risk of developing this or that vs. whether or not they actually have the disorder. It’s not so simple and I suspect my daughter and I will have long discussions regarding screening- both regarding celiac disease and other diseases.

This is a subject none of us will be able to ignore as more and more tests become available to determine genetic risks for this or that disorder. It’s almost like reading a detective whodunnit and ignoring the entire book except for the last chapter; do we really want to know everything about what our genetic makeup tells us what fate may well have in store for us? Don’t get me wrong. I am a strong proponent of screening and early diagnosis, but it depends on the diagnosis and what the benefit might be by the early diagnosis. Screening for “increased risks” is even trickier.

I apologize for not having an entry for about a month- a busy time with the holidays. Best wishes to all for 2008. I want to start out the new year with a case scenario. I promise it won’t be as esoteric as one of Dr. House’s cases (for those of you who don’t watch TV, Dr. House is a rather unconventional medical sleuth).

Case History

The patient is an 18 year old white male named Chad with a history of type 1 diabetes diagnosed at age 10 years. He had generally done well with the diabetes over the years; hemoglobin A1c values had been consistently in the 7-7.5% range (hemoglobin A1c is a blood test that can provide an index of the average blood glucose over the previous 3-4 months). That’s pretty good for a teenager. The patient saw me for a routine checkup in September 2007. Things seemed fine except that I noted a 5 lb. weight loss from the previous visit. There was no change in diet or activity that might explain the weight loss. I suggested that the patient monitor his weight and notify me if he lost as much as another 5 lbs. I scheduled a follow-up clinic visit for December 2007, sooner than I would have normally done so.

Note: Since the patient seemed quite healthy based on my medical history and physical examination, I elected to carry out no special studies at the time of the visit. Some physicians might have done some detective work at that time but I was comfortable to wait and watch.

Two Months Later

I saw Chad for his scheduled follow-up visit in mid-December. He had not contacted me in the interim (I encourage patients to contact me by e-mail whenever they have questions or need something done such as a prescription refill- it works very well and even in my mostly rural state of Missouri, about 90% of families have internet access). The medical history was more or less unchanged except for, perhaps, somewhat less well controlled diabetes. Again, there was no history of anything of concern; specifically, no fatigue, no gastrointestinal symptoms, no change in appetite, no history of drug or alcohol use. The physical examination was unremarkable except for another 7 lbs. weight loss. Now the patient was beginning to look a bit underweight. I was puzzled and concerned.

The Differential Diagnosis

Now it was a question of getting serious about finding out what the problem might be. Eighteen year old males do not lose substantial amounts of weight for no reason. I first decided not to “accept” as fact my medical history. Thus I felt a “fresh” look at the problem was necessary. I first considered if the weight loss was somehow related to the diabetes. Teenage girls with diabetes all know that skipping some of their insulin injections (or turning off their insulin pumps) is the quickest and easiest way to trim down- high blood glucose levels result in large glucose losses in the urine. Every gram of glucose lost is 4 calories lost. It’s not a healthy way to lose weight but it happens. Anyway, I was satisfied that Chad’s weight loss was not from poor diabetes control (a clue would have been the presence of ketone bodies, fat breakdown products, in his urine- urine ketone tests were consistently negative). Next, I wondered about disorders associated with diabetes that might be responsible for the weight loss. Type 1 diabetes is an autoimmune disease and certain other autoimmune diseases are more common in people with type 1 diabetes than in the general population. Chronic lymphocytic thyroiditis causing hypothyroidism is the most common associated autoimmune disorder but I couldn’t have accounted for the weight loss. Hyperthyroidism from Graves Disease is another autoimmune disease slightly more common in people with diabetes than in the general population and this disorder could cause weight loss from an increased metabolic rate. Against the diagnosis was the absence of an enlarged thyroid gland, normal pulse and blood pressure, and absolutely no history of anxiety, poor sleeping, or other typical hyperthyroidism signs and symptoms. Finally I thought about celiac disease, an autoimmune disease of the small bowel caused by intolerance to gluten, a major component of wheat. Celiac disease is currently “in vogue” and recent studies have documented that it is much more common in people with diabetes and in the general population than was previously known; studies show that the prevalence of celiac disease in the general population ranges from about 0.1-1% depending on the study population. The disorder is particularly common in people with northern European backgrounds- Finland has a prevalence of 1-2%. In people with type 1 diabetes, the prevalence is 2-3 fold higher than in the general population but it varies widely depending on the criteria for diagnosis and the characterisitcs of the patient population studied. Patients with celiac disease may have no signs or symptoms pointing to the diagnosis, but a variety of gastrointestinal symptoms are common. Weight loss on the basis of decreased appetite and/or malabsorption is fairly common (remember, Chad had no gastrointestinal symptoms).
One study from Italy published several years ago ( Cerutti et. al., Diabetes Care 2004;27:1294-98) followed 4322 children with type 1 diabetes ages 4-11 years. The investigators found a prevalence of biopsy-proven celiac disease in 6.8% of the children. Risks for celiac disease were increased 3-fold if the diabetes was diagnosed before age 4 years. In 90% of cases, the diabetes was diagnosed prior to the diagnosis of celiac disease.
Back to the detective work- I next considered systemic disorders- medical conditions that could cause weight loss, particularly those without obvious signs and/or symptoms. Thus I considered, inflammatory and infectious conditions (e.g., regional enteritis, tuberculosis, AIDS, other chronic infectious processes); I considered neoplasia (e.g, lymphoma); I considered illicit drug use; I considered an eating disorder (e.g., anorexia nervosa); I considered a chronic anemia- as a primary problem or secondary to another diagnosis.

Moving from Differential Diagnosis to Diagnosis

Next, I needed to take my differential diagnosis and then order appropriate laboratory tests. This is the tricky part. Should I order every imaginable test, just a few, or do one at a time, waiting for results from one before I move to the next? Doing tests one at a time would not have been very practical here- it would have been the least expensive approach but one with the likely possibility of many, many needle sticks and return visits over several weeks. I elected to focus on the most important diagnoses and ordered the following tests: a blood count, blood inflammation tests (erythrocyte sedimentation rate and c-reactive protein) blood chemistries including tests of liver function, a drug screen, HIV testing, thyroid function testing, a chest x-ray, and a celiac test panel (this includes several tests carried out at the same time). So it was one blood stick and one chest x-ray.

Test Results

I should mention that I discussed with Chad why I ordered the tests that I did, including the drug screen and the HIV tests (he readily gave permission for me to order those tests). Next it was time to wait. The results started to come in and one by one they were all completely normal until I was waiting on only the celiac test panel. So he didn’t have a drug problem, AIDS, a hidden infection, hyperthyroidism, etc. What could it be?

Finally, after a week or so the celiac panel came back wildly positive for celiac disease. We had a diagnosis and one that could explain his weight loss. Why he had no gastrointestinal symptoms (other than weight loss), I don’t know. It is interesting that the simple celiac antibody tests (anti-gliadin IgA and IgG) were normal; the more specific anti-endomysial IgA was positive as was the very specific anti-human tissue transglutaminase test (>100 U/ml with normal < 4 U/ml).

The Next Step

So, we had a diagnosis and the next step was referral to a gastrointestinal specialist for maybe a small bowel biopsy and certainly a gluten-free diet. If the diagnosis is correct (with respect to the reason for his weight loss), Chad will begin gaining weight on the gluten-free diet. This last step in diagnosis is important. We want to be certain we have identified the cause of Chad’s weight loss.

Note: Some would argue that we should have screened Chad for celiac disease even before he had any weight loss, given the increased prevalence of the disorder in patients with type 1 diabetes. I have smart colleagues who screen all patient with type 1 diabetes for celiac disease and other equally smart ones who do not. Celiac panels are very expensive and usually “negative.” I would generally screen all patient with type 1 diabetes under age 5 years for celiac disease but not older patients unless there are some signs or symptoms suggesting the diagnosis. I do recommend autoimmune thyroid disease screening for all patients with type 1 diabetes since the prevalence of thyroid disease is 30-40% in patients with type 1 diabetes, the testing is relatively inexpensive, and most patients who will ever develop autoimmune thyroid disease, have “positive” thyroid antibodies at the time they are diagnosed with the diabetes. Maybe, I’ll change my mind about all this next year? That’s clinical medicine- still lots of room for “clinical judgment.”