A Breakthrough In Management Of Type 1 Diabetes?

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I want to call your attention to an article published the other day in the  New York Times (February 5, 2010).  The article was entitled “Insulin Dose Automated In a Study” and written by Natasha Singer.  The article summarized a study just published online in the journal Lancet (5 February 2010) written by Hovorka and colleagues and entitled “Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomized crossover trial.”  There was an accompanying editorial comment entitled “Closed-loop insulin delivery: is the holy grail near?” written by Eric Renard.

If you have access to the full article and the editorial comment, I urge you to read them (it will cost you a bundle unless you have access to a medical school library and have privileges to obtain the articles).  In my opinion, the newspaper article did not really convey the gist of the study in a way that was easy to understand.  In reading the newspaper article I got the sense that some major breakthrough had occurred.  When I read the actual scientific report, I was much less impressed that we were on the brink of “the holy grail” as the title of the editorial comment suggested we might be.

What is a closed-loop insulin delivery system?

In people who do not have diabetes, their insulin delivery is within a closed-loop system.  This means that insulin delivery is automatically regulated based on need.  The cells in the pancreas that secrete insulin (the beta cells) are little computers that read the blood glucose level continuously and secrete insulin as needed to maintain  blood glucose levels in the normal range.  It’s the same idea as with a thermostat on the wall.  It reads the ambient temperature continuously and depending on the particular system, can heat or cool the air as needed to maintain the temperature within a very narrow range.  These are closed-loop systems.  In contrast, an open-loop system doesn’t do things automatically to maintain the status quo.  Someone needs to manually “close the loop.”  With respect to room temperature, it would be necessary to check the temperature and manually adjust the temperature up or down as needed. With respect to diabetes, the standard approach uses an open-loop system approach to adjust insulin injection doses or rates of infusion for people who use insulin pumps, based on blood glucose readings and/or anticipated food intake or activity.  Are you with me so far?

How was the study designed?

The investigators studied 19 patients with type 1 diabetes age 5-18 years.  The patients were treated with either standard continuous subcutaneous insulin infusin (OLCSII) or a closed-loop system (CLCSII).  Remember, the OLCSII is an open-loop system in which the patient adjusts the insulin infusion rate and/or the doses with meals based on fingerstick blood glucose testing.  Comparisons were made between OLCSII and CLCSII overnight, after rapidly and slowly absorbed meals, and after exercise.  Patients were masked to both blood glucose and interstitial glucose levels during all 3 protocols; the sensor glucose levels were interstitial glucose readings obtained almost continuously.  Investigators were masked to blood glucose levels but not sensor readings.  During the overnight studies, the sensor glucose readings were fed every 15 minutes to a computer which calculated insulin infusion rates based on an algorithm.  A nurse then “closed the loop” by manually adjusting the insulin infusion rates.  During nights when the patients used OLCSII, the insulin infusion rate was not adjusted based on either fingerstick blood glucose or interstitial glucose readings.  The primary outcome was time during which plasma glucose levels were in the range 70-144 mg/dL or below 71 mg/dL.

What happened?

The results showed no statistically significant differences between OLCSII (21 nights in 17 patients) and CLCSII (33 nights in 17 patients).  Likewise, there were no statisticallysignificant differences between the treatment groups with the meal and exercise protocols.  A secondary analysis of the data in whch the results from the 3 protocols were pooled showed increased time in the target range (60% vs. 40%) for CLCSII and reduced time with glucose levels below the target range (2.1% vs. 4.1%).  These differences were statistically significant.  The investigators reported that “no events” occurred in the CLCSII group when plasma glucose was below the target range, meaning no hypoglycemic symptoms; in the OLCSII group, 9 events were recorded.  The investigators concluded that CLCSII “could reduce the risk of nocturnal hypoglycemia in children and adolescents with diabetes.”

What does it all mean?

First, it was rather surprising to me that this study made such a media “splash” given that the data showed no statistically significant differences between OLCSII and CLCSII for the primary outcomes data analyses.  It was only with the secondary analyses (after the fact so to speak) that statistically significant differences were shown.  Basically, it was only by “data mining” that the investigators showed statistically significant differences between the two arms of the study that favored CLCSII.  What I am trying to say in polite terms is that the data manipulation in the study was not a very good way to show that CLCSII might be better than OLCSII in preventing nocturnal hypoglycemia in children and adolescents using CSII even though CLCSII might really be quite a bit better.  I thought the investigators actually interpreted their data rather conservatively and hinted that CLCSII might just decrease risks of nocturnal hypoglycemia but that further studies were needed.  Mostly, I agree with their conclusions and found the data interesting.  At the same time, I found the New York Times article a bit over the top with its summary of the study and the possible clinical implications.  It’s not for me to say but I wouldn’t have thought a small study with no statistically significant different outcomes for the primary data analyses between “standard care” and and a new approach would have merited a report on the first page of the Business section of the New York Times.  Maybe I have misinterpreted things?  Since the report was placed in the Business section and not the Science section, maybe it’s all about the commerical possibilities of  CLCSII?

What do the data really mean?

I do not want to be viewed as cynical in my criticism of the New York Times report.  Hypoglycemia is a serious matter and anything we can do to decrease diabetic patients’ risks for hypoglycemia should be embraced.  I would agree that the study was a sort of “proof-of-concept” for the use of a continuous glucose monitoring system and a computer to adjust insulin infusion rates to decrease patients’ risks for nocturnal hypoglycemia.  On the other hand, there was no discussion in the medical article or the newspaper article that previous long-term studies with continuous glucose monitoring using interstitial glucose monitoring as in present study has not shown less hypoglycemia (nocturnal or otherwise) in either children or adults with type 1 diabetes and only minimal overall improvement in blood glucose control in adults and none in children (see New Engl J Med 2008;359:1464-76).  In addition, most hypoglycemia in patients with type 1 diabetes, whether they are being treated with CSII or other types of insulin regimens can be prevented by appropriate adjustments in insulin doses based on fingerstick blood glucose testing.  It is just that such adjustments require patients to be highly knowledgeable about their diabetes and compulsively attentive to their self-care.  That’s not so easy.  Maybe while we’re waiting for a cure, it’s a good idea to work hard on temporary fixes such as closed-loop insulin delivery systems?  At the same time we must be very careful to separate hype generated by those commercial interests dreaming of big bucks and scientific truth.  Fear of hypoglycemia must not push us into expensive treatment approaches that are theoretically useful but cannot be shown to be clinically helpful without resorting to secondary data analyses.

I’m Still Alive

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I knew it had been a while since I last posted an entry, but I was astonished that it had been 2 months.  I apologize for my lazy behavior.  My only real excuse is that I have been following the often painful health care reform news and wanted to wait to write anything about it until there was (or maybe was not) an actual bill to discuss.  I’m still waiting.  But, I do want to mention 2 recent articles of interest.  The first was a nice discussion about hair loss in women.  The article entitled “When Hair Loss Strikes, A Doctor Is a Girl’s Best Friend,” and written by Lesley Alderman appeared in the New York Times on Saturday January 16, 2010.  It is a nice summary of the major causes and treatments for female hair loss, some of which are endocrine.

I would only add to the discussion that in some instances, hair loss is on an auto-immune basis (called alopecia areata if the hair loss is spotty or alopecia totalis if the loss is big time) and is strongly associated with certain other auto-immune disorders, particularly chronic lymphocytic thyroiditis (aka Hashimoto’s thyroiditis) and adrenal insufficiency.  If the hair loss is considerable and sustained over weeks-to-months, I would strongly recommend a visit to a dermatologist before embarking on potential therapeutic misadventures.

The second article which appeared in the New York Times Magazine on Sunday January 17, 2010 was written by Tom Dunkel and was entitled “Vigor Quest.” The article was a very interesting and surprisingly balanced discussion of the attempts by what appears to be an increasing number of people obsessed with prolonging their youth, or at least, their youthful performance in a variety of activities.  My interest in the subject is, of course, as an endocrinologist (not as an aging endocrinologist).  Much of the discussion in the article focused on testosterone and growth hormone, drugs about which much has been written in both the medical and non-medical literature.  The subject has been in the news quite a bit recently with the controversy surrounding use of these drugs in professional athletes.  There is no question that deficiency of either testosterone or growth hormone can impair athletic performance and affect overall vigor.  The still unanswered questions are whether taking one or both of these substances when there is no apparent deficiency can be helpful and if there are potentially serious side-effects.  It is good that the National Institutes of Health has embarked on a long-term (6 years) study of the potential mental and physical benefits of testosterone therapy in elderly men.  They should also consider a companion study of growth hormone.  I for one strongly recommend that until we have much more scientific information, use of these biological agents be limited to patients who have definite deficiencies and symptoms and signs to match the laboratory findings.  But, I just wonder how fast I could swim if………?

Making Health Care Better: What We Can Learn From Intermountain Healthcare

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FYI

I strongly encourage all of you to read an article that appeared in last Sunday’s New York Times Magazine section.  The piece was written by David Leonheadt and entitled “Making Health Care Better.”  The article discussed in some detail the work Intermountain Health Care (IMHC) was doing to improve patient care.  IMHC is located in Salt Lake City, Utah and is a consortium of hospitals and clinics in the region.   For quite a number of years, the organization has focused on developing treatment protocols based on data and analyzing their outcomes.  The article focused on Dr. Brent James, the Chief Quality Officer of the organization and the extraordinary successes the group has had in improving patient care.  There is much for all of us to learn by reading the article.  After you finish the article I suggest you read “The Bell Curve,” written by Atul Gwande as it ties in nicely (if you are feeling worn out after reading the Leonheadt article, you could cheat a bit by reading my entry last year about the Gwande article, but I’d rather you read the article itself).

Does Exercise Decrease Risk Of Heart Attack?

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I confess that I am not a compulsive reader of obituaries.  On the other hand my wife, who is an attorney, picks up our local paper and first turns to the obituary page to find out if any of her clients has died.  I guess that’s important for attorneys to know.  I did, however, read an obituary published in the New York Times today (Sunday, November 8, 2009).  The piece was written by Dennis Hevesi and was entitled “Jeremy Morris, 99 and ½; Proved Exercise Is Heart-Healthy.”  Years earlier I had read most of Dr. Morris’s papers but I had completely forgotten about him and his research although what he taught me is firmly implanted in my approach to medical care.

Bus drivers vs. conductors

Dr. Morris was a British epidemiologist who hypothesized in the 1940’s that one could prove that exercise was heart-healthy by studying  bus drivers and conductors on London double-decker buses.  Drivers spend 90% of their workday sitting down while conductors walked up and down the bus stairs about a million times each day (actually about 600 stairs per day).  In a paper published in 1953, Dr. Morris showed that heart attack rates were dramatically lower in the conductors.  Follow-up studies showed that although the conductors, on average weighed less than the drivers, the rates were not closely related to weight or body type, including waist size.  He later studied postal workers, clerks and telephone operators vs. those who delivered the mail by walking or by bicycling.   The delivers had much lower risks of heart attack.  The strongest proof for the relationship between physical activity and risk for heart attack came from studies Dr. Morris conducted in the 1960s.  He looked at heart attack risks in a large group of men with sedentary government jobs in relation to their degree of aerobic activities outside work.  He found that those who performed vigorous exercise on a regular basis had a 50% risk reduction for heart attack.  The importance of Dr. Morris’s studies cannot be overemphasized.  In my opinion, most of what we now know about exercise and cardiovascular health was the direct result of his ground-breaking work.

The limitations of epidemiologic studies

Not to diminish the importance of Dr. Morris’s work, I need to remind you that epidemiologic studies cannot prove cause and effect but only show relationships.  For example, maybe bus drivers, postal clerks, and office workers are under more stress than bus conductors and postal delivery personnel?  And maybe people who have sedentary government jobs and who don’t exercise regularly just have different personality types (e.g., ‘type A” vs  whatever) than those who do exercise regularly and that is the reason for the study findings?  Anyway, it’s a pretty good bet that it’s the exercise per see that lowers the heart attack risk.  By the way, it may just be a fluke but Dr. Morris exercised regularly his whole life and lived to 99 and ½ and didn’t die of heart disease.

Is it a big thyroid gland or what?

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I haven’t looked in my archives, but I vaguely remember writing something quite a while back about enlargement of the thyroid gland, which is commonly called a goiter (the term is from the Latin “gutter” meaning neck).  It’s time to talk about goiters again.  Last week I received an e-mail from an obviously worried patient whose primary care doctor had just told her that she had an enlarged thyroid gland and that a blood test the week before had come back abnormal and that a thyroid ultrasound needed to be performed ASAP.  The patient asked me if I had ever noticed that she had an enlarged thyroid gland.  I answered her e-mail and in it asked that the doctor fax me a copy of the abnormal test result.

Back to basics

Before I tell you anything about the patient’s medical history and what I wrote in the e-mail (as well as a subsequent one, when I got the lab test result), I think we should review a bit about the anatomy of the thyroid gland.  The gland is in the neck just below the larynx or so-called Adams apple.  The gland is palpable in most people but it takes some practice to feel a normal-sized gland.  First have the person sit in front of you and just look at their neck.  If you notice a small protuberance just below the larynx go up and down when the person swallows, you have probably seen the thyroid gland.  In precise anatomic terms, the gland is situated just below the cricoid cartilage ring which is the first ring below the larynx.  The space between the bottom of the larynx and the cricoid cartilage is called the crico-thyroid membrane and it’s the place one is supposed to lance with a fountain pen cap to save a person’s life if there is an obstruction to airflow at the larynx.  I wonder if anyone has actually done such a thing?  I wonder how many people even own a fountain pen?  Anyway, the thyroid gland consists of an isthmus in the midline which connects the 2 lateral lobes.   With a normal-sized gland, the lateral lobes are quite small but most of the time the isthmus can be palpated with practice.  If one sits facing the patient and the light is right, it is usually possible to see a butterfly-shaped form move up and down the neck with each swallow; the body of the butterfly is the thyroid isthmus and the wings are the lateral lobes with the superior lobes much more prominent than the inferior ones.

Back to the patient

I was astonished when the patient asked me if I had ever noticed that she had an enlarged thyroid gland.  In fact, I had been caring for her type 1 diabetes for many years and had noticed first many years back that she had a very prominent neck.  She and I had talked about her neck on many occasions- that should tell all doctors just how much patients listen to what the doctors says at clinic visits!  I had known that the neck prominence was clearly not the result of a goiter since when she swallowed, the mass did not move up and down; the “problem” was simply a combination of large neck muscles and a fat ring that sat just above  the thyroid isthmus which was barely palpable.

I had obtained thyroid function studies on a number of occasions, all of which were normal.  The tests had been ordered as a routine since about 25% of patients with type 1 diabetes have chronic lymphocytic thyroiditis, an autoimmune disorder.  I had also ordered thyroid function studies about 2 years earlier when the patient developed menstrual irregularities.  Her thyroid test results had always been normal.  So, it was not a surprise when I got the faxed copy of the thyroid test the patient’s primary care doctor had ordered that it was normal.  I don’t know why the doctor told the patient the test result was abnormal.

So, I e-mailed the patient and told her not to bother with the ultrasound and that we would rediscuss her thyroid gland at the next appointment.  I also told the patient that the primary care doctor was just trying to do a good job and that sometimes it’s hard to tell if a thyroid gland is enlarged even though as we discussed above it’s pretty easy if one knows how.

One more thing: the value of medical histories and physical examinations

This case should serve to remind all physicians that obtaining good medical histories and performing appropriate physical examinations remains an important aspect of medical encounters.  Many years ago I found a cartoon in a throw-away medical journal for resident physicians.  The cartoon showed two young physicians entangled in x-rays and laboratory test reports looking puzzled.  One of the physicians was turned towards the other and said “maybe we should go back and get a medical history and do a physical examination.”  I saved the cartoon because even in “the old days” there was concern that physicians were relying too much on laboratory tests to “make the diagnosis” without first starting with the tried and true.  It amazes me how few of the younger physicians are skilled at obtaining medical histories and performing physical examinations.  The stethoscope has largely turned into just a prop to hang around the neck.  It’s time to resurrect the art and science of histories and physicals.  Patient care will be all the better for it.  I wonder how much my old cartoon would bring on E-Bay?

Fighting Fat: Update on New Obesity Drugs

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First, I just want to let you know that the article on Hawaii’s health care system that I discussed in my last entry can be found on the front page of the printed version of the New York Times for Saturday October 17, 2009.  Read it, particularly if you have gotten depressed about the possibilities for health care reform.  There is hope.  Second, I wanted to let you know about another noteworthy article in the same New York Times issue.  The article is entitled ” Medicine’s Elusive Goal” and was written by Andrew Pollock.

The article summarizes the latest information about medications for treating patients with obesity, focusing on 3  promising new drugs.  If any of you have read my past entries about obesity, you would know that I am not Mr. enthusiasm about using drugs to treat obesity.  First, none to date have been shown to be very effective in the long run (e.g, after 5 years) and I am very concerned about side effects that may develop- remember fenfen.  Anyway, the article is quite well done (as are all of the previous pieces from Mr. Pollock that I have read) and I recommend it to you.

I just urge you as a health care provide or, perhaps as a person with a “weight problem” to remember that being significantly overweight is not good for one’s health and that it’s still all about calories in vs. calories burned up.  The potential benefits  of the various treatments for obesity, current and future must be weighed against the treatment risks, known AND unknown.  That’s not very easy math.

You’ve Got To Read This If You Are Interested In Health Care Reform

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I know I haven’t written anything for a while now but I promise to get back to work.  But I have exciting news for those of you who have not already given up on following the health care reform debates.  I just read an article in the New York Times (online 10/16/09) that should be must reading.  The article is entitled “In Hawaii’s health system, lessons for lawmakers” and was written by Gardiner Harris.   The article summarizes the approach to health care coverage in Hawaii and the incredible success story.  It is interesting that the Hawaii “story” is just now being discussed but better late than never.  Read the article.  Then, let me know what you think.

Help, Help, I’m Drowning In The Health Care Reform Storm

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I have stayed away from my website for a number of weeks for fear that I would be driven to  write about the current craziness surrounding the various competing health care reform proposals; I couldn’t figure out what I could write that would accomplish anything other than make me feel better about the chaos.  I’ve changed my mind; I am ready to offer a few unsolicited comments.

Let’s not forget why health care reform is desperately needed

In recent debates I have heard little about why health care reform is needed anyway.  The fights (?debates) have become more and more emotional and less articulate; the debate now seems to be more about politics and name-calling than anything substantive.  Please, please let’s all remember that our health care system is a mess and a very expensive one.  If we don’t fix things, we as a society will be diminished in many ways.

Why is the path to health care reform proving to be so difficult?

I cannot really understand if the Obama administration was so naive or so misinformed or both about the challenges that would face any meaningful reform efforts.  I think they understand now.  As I tried to point out in an entry last month,  any efforts to introduce meaningful reforms would be met with fierce opposition from those who felt they had something to lose.  How could anyone believe that health insurers, big pharma, hospitals, doctors, etc., would sit by and cheerfully accept changes in the system that tore into their revenue streams?  Yet we seemed to act that way.  Now, even the “common folk” are up in arms about what they see as provisions in health care reforms that will adversely affect them.  To add insult to injury, those politically opposed to the Obama administration see the health care issue as one which may give them an opportunity to “break” Obama.  So, it’s pretty easy to understand how we got where we are now in the debate.

What do we need to do to get back on the pathway to reform?

I believe that we need to back up and all take several deep breaths and think about the priorities.  In my opinion, the single biggest and scariest problem is the looming bankruptcy of Medicare.  More than 40 million Americans count on Medicare and the numbers are growing daily as our baby-boomers find they’re not babies anymore.  Depending on whose estimates you use, the program will be out of money in 2-5 years.  This is a CRISIS.  We need to address it now.  I don’t want to bore you with the details on how to fix it but you might want to check out some of my earlier entries for suggestions.  The bottom line is that we need to cut costs drastically while improving the program for seniors.  Medicare reform will be ( maybe I should be cautious and say “can be”) the template for fixing the rest of what ails the health care system.

I don’t care what side of the political spectrum you might be on and what your philosophy might be about the role of government.  If we do not fix our healthcare system we will all suffer.  In my opinion almost nothing in the current health care reform proposals ( or in the opposition to those proposed reforms) will take us to where we need to go.

Health Care Guidelines:Should Physicians Be Required To Follow Them?

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I just want to call your attention to a very important article in yesterday’s New York Times (18 August 2009, page B1).  The article was entitled “Diabetes case shows pitfalls of treatment rules,” and was written by Barry Meier.  The article discussed the controversy surrounding a national guideline for treating patients with diabetes that was written in 2006 and withdrawn last year.  Basically, the national guideline recommended aggressive treatment of high blood glucose levels in all patients with diabetes only to reverse its recommendations; new data showed that for some patients, following the guidelines would increase morbidity and mortality.  The specific details of the case are important but perhaps not so important as the information it provides regarding how medical treatment guidelines are established and their pitfalls.

So-called national guidelines, consensus statements, and expert opinions should all be viewed with considerable suspicion since they are often put together by many interested parties with very different points of view.  Typically, such treatment guidelines are compromises hammered out among physician experts, insurers, special interest groups and are anything but “consensus statements.”  The problem with consensus statements and treatment guidelines put together by expert groups is that however incorrect they might be, individual physicians who ignore these guidelines when treating their patients run the risk of not having the treatments covered by health insurance or by risks of malpractice lawsuits when results are not satisfactory.  Anyway, I highly recommend that you read the article and I can asure you that my recommendation was not put together by a committee.

The U.S. Health Care Debate: Is There Really A Debate?

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Over the past few months I have grown increasingly dismayed by the so-called “debate” on reforming the U.S. health care system.  In my opinion, what started as a mostly civilized discussion, has devolved into chaos; it  would be nonsense to describe the current goings on as meaningful discussions and clearly not a debate in the usual sense of the word.

I have been astonished at many of the statements I had heard from what I had formerly thought were reasonably intelligent elected officials.  I have been no less amazed at the statements from the general citizenry; the amount of misinformation out there is now almost impossible to counter with truth.

Here I am not trying to “peddle” any particular health can plan but only that some degree of sanity enter into the discussions.  In my opinion,  the problem is two-fold.  First it’s that those satisfied with the status quo (insurers, pharmaceutical companies, consumers who are satisfied with their health insurance, etc.) don’t want to risk any meaningful changes in the health care system.  Maybe they aren’t entirely happy with the status quo, but they fear that any changes in the system will be much, much worse.  What is that expression, something like “the devil you know is better than the one you don’t?”  The second aspect of the problem is that politics have gotten in the middle of things (big surprise).  It is clear that President Obama really wants health care reform.  Those opposed to his presidency, believe that failure of the President to achieve his  health care reform goals will “bring him down.”

I have no idea how things will end up.  I am not optimistic that anything good will rise out of the mess.  If I were running the show, I would back up and start over.  The first thing we need is a small group of experts to lay out a blueprint for a health care system as it would exist in the future.  The blueprint needs to deal with all of the current components of the system including private insurance, Medicaid, Medicare, the VA system, the U.S. Military health care system (troops and their families), and those people currently without any health care coverage.  We need to consider how all of these components would fit together or at least coexist.  We also need to consider how we would cut costs and slow the rate of future cost increases since, we can’t possibly afford universal health care without controlling costs.  We also need to decide how we would pay for health care.  There aren’t many options- a payroll tax, higher income taxes, a national sales tax, that’s about it.  We haven’t had these critical discussions yet (call it a debate if you wish) and we can’t really move forward without a comprehensive look at what the experts think the system should look like when it’s all put together in about 20 years (if we’re lucky).