Last week I had a very interesting clinic in which the first 3 patients were teenagers with type 1 diabetes.  The first patient was a 16 year old boy with onset of diabetes at about age 6 years.  He was being treated with an insulin pump and had always done extraordinarily well with his diabetes care.  He never missed clinic visits, he tested blood glucose levels 4-6 times daily, he made appropriate insulin dose adjustments, and he never had a hemoglobin A1c over 7% (that’s the test that measures overall blood glucose control during the preceding 3-4 months and is a strong risk predictor for the development of diabetes complications).  The second patient was a 16 year old female with onset of diabetes at age 7 years.  She was being treated with an insulin pump and had always done reasonably well with her diabetes.  She rarely ever missed clinic visits, she tested blood glucose levels 3-4 time daily and usually made appropriate insulin dose adjustments.  Her hemoglobin A1c levels had been consistently in the 7.5-8% range.  The third patient was a 16 year old female with  onset of diabetes at age 9 years.  She was being treated with an insulin pump and had never done particularly well with her diabetes self-management.  She tested blood glucose levels 1-2 times daily at most and not at all on some days.  She had a history of several hospitalizations with diabetic ketoacidosis.  She occasionally missed clinic visits.  Her hemoglobin A1c values had been in the 8.5-9% range up until about age 12 years, and in the 11-12% range thereafter.

Enter the “shadowing” students

That particular clinic day I had 2 undergraduate pre-med students following me around- they call that activity “shadowing,” and the idea is that students can get a feel for  what medicine practice is really like before they actually decide to make a career of it.  One additional practical reason for pre-med students to shadow is that most medical schol admission committees look more favorably on applications that list shadow experiences than those that do not (personally, I wouldn’t think more or less about an applicant based on his or her shadowing experiences).  Anyway, after we had seen the 3 teenagers with diabetes, one of the students asked me why the first patient was doing so well and the last patient so poorly.  It was a great question but I was not able to give a very good answer.  I told the student that I didn’t really understand why some patients with diabetes do so well and others so poorly, even when cared for by the same physician.  We then had quite a long discussion about what is known about patient compliance and why the question was so important in diabetes.

Why Do Patients With Diabetes Develop Chronic Complications?

First, the chronic complications of diabetes can be divided into so-called “microvascular complications,” those of the eyes, kidneys, and nervous system, and “macrovascular complications,” those of the heart and blood vessels.  Although we still have an imperfect understanding of the precise mechanisms responsible for the various complications, we do know  there are 3 principal risk factors involved: blood glucose levels, blood lipid levels, and blood pressure levels.  These risk factors account for approximately 90-95% of the risks for the development and progression of the various diabetes complications.  These risk factors are also treatable and I don’t think I am being overly optimistic when I say that we know how to prevent almost all diabetes complications.  Yet, many patients with diabetes are still developing these devastating complications at enormous personal and societal costs.  So, what gives?  This is really the question that my shadowing student asked.

Over the next few weeks, in a series of entries, I want to explore this question of why some patients with diabetes do better than others.  Perhaps, that is the most important question we should be asking these days in the management of patients with diabetes.  If we can come up with some answers, perhaps, short of a cure, we can have a menaingful impact on long-term outcomes.

Results from a very interesting and important study were  published in this week’s New England Journal of Medicine.  The study was entitled “Glucose Control and Vascular Complications in Veterans with type 2 Diabetes,” and written by W. Duckworth and colleagues, members of the Veterans Affairs Diabetes Trial  (VADT).

The purpose and design of the study

The primary goal of the study was to determine if intensive treatment of diabetes decreased risks of developing major cardiovascular outcomes defined as a composite of myocardial infarction, stroke, death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary artery disease, and amputation for ischemic gangrene.  Development/progression of microvascular complications was also monitored.

The study population consisted of 1791 military veterans who had a history of suboptimal response to therapy for type 2 diabetes.  At onset, the average duration of diagnosed diabetes was 11.5 years and 40% of the patients had already had a major cardiovascular event.  Patients were randomly assigned to either an intensive-therapy (IT) group (IT) or a standard-therapy (ST) group with an operational goal of achieving, on average, a 1.5% reduction in HbA1c in the IT group.

The treatment regimens consisted of 2 oral agents, metformin and rosiglitazone for both IT and ST patients with BMIs 27 or more, and glimepiride and rosiglitazone for those with BMIs less than 27;in the IT patients, maximal doses of the medications were given but only 50% of the maximum in the ST patients.    Insulin was used as needed throughout the study in those IT patients with HbA1cs 6% or greater and in ST patients with HbA1cs less than 9% (I confess that I didn’t understand the rationale for their treatment protocol and it was not clearly addressed anywhere in the report).  Investigators were free to use any medications they wished throughout the study with the understanding that the goal was to lower HbA1c levels in the IT patients

Results

Study patients were enrolled between December 2000 and May 2003 and followed until May 2008; follow-up was for a maximum of 7.5 years and a minimum of 5 years.  Mean Hb1c at baseline was9.4%.  Mean HbA1c in the IT and ST groups stabilized after 6 months at 8.4% in the ST group and 6.9% in the IT group.  The results showed more or less no differences between the treatment groups for any of the outcomes, cardiovascular or microvascular; sudden cardiovascular deaths were about threefold increased in the IT group but rates of death from cardiovascular causes were similar in the two treatment groups.

What do these results mean?

At first glance, these results are rather depressing; they seem to be telling us that improving risk factors for diabetes complications in paients with type 2 diabetes is of no benefit.  I would not be so quick to jump to such a conclusion.  First, cardiovascular risk factors were controlled similarly in both treatment groups- too bad there wasn’t a third treatment group where these risk factors were not controlled.  Second, the ST and IT groups both showed clinically significant decreases in HbA1c levels, the IT group from 9.4 to 6.9 and the ST group from 9.4 to 8.4.  So, were the decreases in outcome risks in the ST group large enough to mask any additional benefit from the lower HbA1cs in the IT group; in essence, what would the results have been if the ST group mean HbA1c had remained at 9.4%?

It is also important to consider the fact that as a group, the study population had longstanding diabetes with poor glycemic control as well as a high prevelance of cardiovascular risk factors (and actual cardiovascular disease).  Should one expect things to “turn around” after only about 5.5 years follow-up on average?  Finally, I hesitate to mention that both study groups were being treated with rosiglitazone, a drug well known to increase cardiovascular disease, particularly congestive heart failure.

The bottom line

So, as I mentioned earlier, this is an important study BUT I would not jump to unwarranted conclusions given the flaws (Maybe more peculiarities than flaws) of the study design, particularly the fact that the HbA1c level fell appreciably in the ST group.  I do not see any reason why a patient with diabetes mellitus, type 1 or 2 shouldn’t strive to improve all known risk factors for diabetes complications while also working hard to minimize the attendant risks, such as increased risks of hypoglycemia.  I am looking forward to see how the “experts” deal with this study.

There was a short but interesting article in the New York Times today entitled “Researchers Report Advances in Cell Conversion Technique,” written by Nicholas Wade (NYT Thursday Aug 28, 2008, page A16). The article summarized a scientific report published today in the journal Nature. Basically, scientists at Harvard University have taken a new tack on finding a cure for type 1 diabetes. Type 1 diabetes is a condition caused by destruction of the insulin-producing cells in the pancreas which are called beta cells. In most instances, destruction of the beta cells is caused by an aut0immune process, in which the body’s own immune system attacks the beta cells.

Maybe stem cells aren’t needed after all?

The researchers used a technique called cell conversion in which they “captured” master proteins called transcription factors which had been previously shown capable of causing adult cells to revert to their embryonic state. So, the researchers first identified the transcription factors critical for insulin production in beta cells. Then they introduced them into a virus known to infect non-beta pancreas cells (those cells that produce digestive enzymes). Next they made mice diabetic by giving them a drug that destroyed their beta cells. Finally they infected the mice with the virus. Bingo- the infected pancreas cells were transformed into non-beta pancreas cells that produced gobs and gobs of insulin. Apparently the transformed cells not only produced insulin, but they looked like beta cells and stopped making the digestive enzymes which had been their raison d’etre. Pretty exciting stuff.

Is there a catch?

These findings are very interesting and potentially could lead to a cure for type 1 diabetes. We shouldn’t get overly excited just yet because there are some important unanswered questions. We already know how to harvest human beta cells that will produce insulin when transplanted into humans. The problem is that the transplanted cells get destroyed fairly quickly by the same autoimmune process that caused the person’s diabetes in the first place. Taking immune suppression drugs helps some but that approach has its own problems. Anyway, it will be very interesting to see how this work progresses and maybe, just maybe, the transformed cells will not be so attractive to the body’s immune system.

In my last entry I provided some tips for non-experts on how to make sense out of medical journal articles. The main purpose of the entry was to provide a framework for analyzing the results of 2 important diabetes studies that were published in the New England Journal of Medicine about 3 weeks ago (Volume 358). Accompanying the reports were 3 editorials, so you can tell the studies were either very important or very controversial.

The first study was called ACCORD, which stands for Action to Control Cardiovascular Risk in Diabetes; the second was called ADVANCE, which stands for Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (I don’t know how clinical trials come up with these bizarre titles- maybe they have a contest and give a prize for the title that provides the best acronym?). Both studies were large-scale clinical trials designed to assess the effects of “tight” glycemic control on cardiovascular outcomes in people with type 2 diabetes mellitus.

The Study Designs

In many ways the 2 studies were very similar. Both studies recruited large numbers of patients with type 2 diabetes (10,251 people in ACCORD and 11,140 in ADVANCE). The average ages and durations of diabetes were fairly similar in the 2 studies (average age was about 60 years and average duration of diabetes was about 10 years) and both had quite a few more male than female participants (about 60:40 ratio). In both studies, patients were randomly assigned to either intensive or standard therapies. The goals of the intensive therapy was to bring hemoglobin A1c levels as close to normal as possible- less than 6% in ACCORD and 6.5% or less in ADVANCE (remember, that’s the test that more-or-less averages the blood glucose level over the previous 3 months or so). In both studies, the primary research question was whether intensive therapy (that was designed to achieve blood glucose levels as normal as possible) would decrease cardiovascular outcomes compared to standard therapy. Patients were eligible for the studies only if they had prior cardiovascular events or had cardiovascular risk factors (in addition, patients were eligible for the ADVANCE study if they had only prior major microvascular events).

The treatment strategies differed in the 2 studies. In the ADVANCE study, patients in the intensive treatment group all received gliclazide, a sulfonylurea drug and any other medications selected by the treating physicians but no sulfonylureas besides gliclazide (a major sponsor of the study was the pharmaceutical company that makes gliclazide). Patients in the standard group could be treated with whatever medications the treating physicians selected but no gliclazide. In the ACCORD study, patients were treated with whatever medications the treating physicians selected but only certain medications were provided free-of-charge by the study (the drug list did not include any insulin preparations).

Study Results

The ACCORD study was stopped after 3.5 years when results showed a statistically increased risk of death in the intensive treatment group with 257 vs. 203 deaths in the standard treatment group. Average hemoglobin A1c in the intensive group was 6.4% vs. 7.5% in the standard group- the average was about 8.1% in both groups at study onset. In terms of well documented cardiovascular outcomes, the intensive group actually had fewer than the standard group but the difference was not statistically significant. Of course, it is likely that the excess deaths were actually cardiovascular in nature. It is interesting that patients in the intensive treatment group with hemoglobin A1cs less than 8% who had no major cardiovascular events prior to entering the study before entering the study, actually had a significantly lower risk of fatal or nonfatal myocardial infarction than patients in the standard group.

In the ADVANCE study, median follow-up was 5 years. Average hemoglobin A1c in the intensive treatment group was 6.5% vs. 7.3% in the standard group. Patients in the intensive group showed a statistically significant decrease in the risk of developing a composite of major macrovascular and a microvascular outcomes, primarily related to a decrease in the risk of developing kidney disease in the intensive therapy group. There was no statistically significant decrease in the risk of developing major macrovascular disease, cardiovascular death, or death from any cause in the intensive treatment group compared to the standard treatment group.

Now What?

So, here we have 2 large-scale clinical trials in patients with type 2 diabetes with somewhat different results: In the ACCORD study, intensive treatment patients were more likely to die than standard treatment patients, while in the ADVANCE study, patients in the intensive group were less likely to develop kidney disease but not more or less likely to develop cardiovascular disease or die than standard treatment patients. Whom are we to believe?

First, were the increased deaths in the ACCORD study intensive group patients “real” or just a statistical fluke- if the study had gone longer or if it had included more patients, would the results have been the same? Based on the statistical analysis, there was about a 1 in 20 chance the results were statistically different between the treatment groups only by chance. We’ll probably never know.

Second, if the increased deaths were “real,” how come? Were there any differences in the design of the two studies that might explain the differences in results? In my opinion, there were major differences in the design of the 2 studies. Most important, the diabetes medication profiles between the 2 studies and even between groups in the ACCORD study were strikingly different. The use of thiazolidinediones, drugs already implicated in increased risks of cardiovascular deaths and deaths from any cause, were used heavily in the ACCORD study but not in the ADVANCE study. In fact, those drugs were used much more in the ACCORD intensive treatment patients than in the standard treatment patients. That fact alone raises serious questions about the meaning of the ACCORD results- were the increased deaths in the ACCORD intensive group patients somehow the result of the lower average blood glucose levels or the result of the medications employed to achieve those blood glucose levels?

Should We Have Expected To See A Benefit From Intensive Therapy?

I hate to further complicate things, but sitting in an armchair I would not have expected to see much of any differences between the treatment groups in either of the studies. In a number of earlier entries I have discussed the results of the landmark Diabetes Control and Complications Trial- the study that first showed in convincing fashion that intensive therapy prevented diabetes complications. In that study, which included only patients with type 1 diabetes, the intensive treatment group maintained hemoglobin A1c at about 7.3% with the standard group at about 9%. It took 9 years to show meaningful differences in outcomes between the 2 groups. Further, the data showed that risk for diabetes complications was directly related to hemoglobin A1c levels. The relationship was not, however, linear; the relationship was exponential- in the hemoglobin A1c range 6-8% there was a slowly increasing risk for complications as the hemoglobin A1c increased which rose rapidly beyond 8% or so. Thus, lowering the level of hemoglobin A1c from 7.5 to 6.4% as in the ACCORD study and from 7.3 to 6.5% as in the ADVANCE and for only a few years would not have been likely to show much of a difference in results between the treatment groups (in the DCCT, it took 24 years to show a clinically and statistically significant difference in cardiovascular outcomes between the treatment groups!).  There was a statistically significant decrease in the risk of developing diabetic kidney disease in the ADVANCE intensive treatment group compared to the standard treatment group but the benefit was tiny (18 vs. 20% risk).

Where Do We Go From Here?

In my opinion, these studies taken together illustrate the dangers in making patient care decisions based on the results of clinical trials. You should have seen the headlines- “study results turn medical thinking on its head,” with “experts” telling us that perhaps “tight” glycemic control in diabetes is not as good as “semi-tight.” In fact, we should be very cautious about coming to any conclusions based on the ACCORD and ADVANCE studies despite the investigators’ best intentions. Don’t say I didn’t warn you in my last entry about the pitfalls of believing what you read.

Recently, I have been asked more and more what the difference is between type 1 and type 2 diabetes and whether there is really a type 2.5. The questions have come not only from patients of mine and friends (who may or may not have diabetes) but also from a surprising number of attorneys. Why the attorneys? It’s because of the now well-known association between certain medications called “atypical antipsychotics” and the greatly increased risks for developing type 2 diabetes. There have been quite a number of lawsuits against manufacturers (both individual and class action) regarding the link between the medications and the development of diabetes, primarily related to the issue of insufficient warning to patients about the risks. There has also been a question of whether some manufacturers hid data from the FDA showing links between their drugs and the development of diabetes. I am not an attorney and have no opinion regarding these legal issues.

Back to the basics: What is diabetes and what is the difference between type 1 and type 2?

I have discussed these topics to some extent in earlier entries but it is worth revisiting the subject. You may want to search my archived articles- maybe I discussed these issues better earlier?

Diabetes mellitus or “sugar diabetes” (to be distinguished from diabetes insipidus, a condition related to poor control of water balance) is a group of disorders characterized by 3 basic features: insulin deficiency, which can be absolute (e.g., destruction of pancreatic beta cells) or relative (e.g, resistance to the release and/or action of insulin); hyperglycemia (high blood sugar levels) as a consequence of the insulin deficiency; and increased risks for the development of certain chronic complications of the eyes, kidneys, nerves, and cardiovascular system (heart and blood vessels).

It is worth adding that for all types of diabetes mellitus, the complications are caused by the same factors which include chronic hyperglycemia, hypertension, and abnormalities in blood lipids (e.g., hypercholesterolemia). It is also important to note that the complications are preventable, regardless of the diabetes type.

The confusing history of diabetes nomenclature

Early on (from the time of the ancient Greeks until the 1920s) diabetes mellitus was just diabetes mellitus. There was a form that mostly affected young children and was more or less fatal within weeks and a form that affected adults who were overweight, and was considered mild (I have no idea what “mild” meant). These 2 forms came to be called juvenile-onset diabetes and maturity-onset diabetes. These terms were widely used between about 1940-1970. Both types were considered to be the same disease with the same genetic basis, just different clinical presentations at different ages. In fact, that’s what I was taught in the 1960s.

Enter the age of semi-enlightenment

By the early 1970s, data were accumulating that the two forms of diabetes might be genetically distinct. There was strong support to rename the diabetes forms based on the degree of insulin deficiency. Thus came the terms “insulin-dependent diabetes” and “non-insulin-dependent diabetes,” or “IDDM” and “NIDDM.” This was a very bad idea and within a few years it became clear that if we were dealing with 2 different genetic disorders, defining them by whether or not the patient required insulin to maintain reasonable blood sugar levels (back then, we didn’t really even know how to quantify what was a “reasonable” blood sugar level) was illogical.

So, by the late 1970s, IDDM and NIDDM were scrapped and replaced by terms meant to reflect distinct genetic and etiologic differences between the diabetes types. The new terms were type 1 and type 2 diabetes. Type 1 was more or less synonymous with the old juvenile-onset diabetes, although the condition could present at any age, and type 2 with the old maturity-onset diabetes, although the condition could also present at any age (e.g., in obese teenagers). Type 1 diabetes is considered to be mostly (not all cases) autoimmune destruction of the pancreatic beta cells. Type 2 diabetes is considered to be a combination of insulin resistance and some true deficiency of insulin secretory capacity. Thus a person could have type 2 diabetes and require treatment with insulin, not just treatment with weight loss, diet manipuation, and so-called oral agents.

Type 2.5

Over time, it became clear that in some cases it was virtually impossible to classify a patient as having either type 1 or type 2 diabetes. For example, what if a 39 year old who was overweight presented with a two-week history of increased thirst and urination, had ketoacidosis (a sign of severe insulin deficiency) but no evidence of autoimmune destruction of the pancreas? And what if this patient had a strong family history of what would be considered typical type 2 diabetes? Is it type 1 or type 2 diabetes? This is where the idea of type 2.5 came about (some people use the term “double diabetes” and I’m sure there are lots of other terms floating about). Could a person have both type 1 and type 2 diabetes? Of course they could; type 2 diabetes is very common and there is no reason that a person who gets type 1 diabetes cannot also have the genes for type 2 diabetes, which would be much more likely to be expressed if the individual were overweight.

Is it important to determine which type of diabetes a person has?

In most instances (probably 95%) it is easy to classify a patient as having either type 1 or type 2 diabetes and to treat them accordingly. Occasionally, it’s virtually impossible to be certain which type of diabetes it is. But, in most instances, it doesn’t really matter. The treatment goals for types 1 and 2 (and type 2.5) are the same. Many with type 2 diabetes can achieve well-controlled diabetes (these days we do know how to quantify the degree of “control”) with weight loss, diet manipulation and, if necessary oral agents. Some patients will require insulin treatment.  We know that type 2 diabetes patients do have some degree of actual insulin deficiency which can worsen over time, particularly if the diabetes has not been well-controlled (there is a strong genetic difference between patients with type 2 diabetes who have a high degree of absolute insulin deficiency and those whose insulin deficiency is mostly insulin resistance). So, these days diabetes treatment is based on achieving therapeutic goals not what type of diabetes it may be. If a patient needs insulin to achieve treatment goals, they need insulin. It’s really that simple.

There are actually some reasons to know if a patient has type 1 or type 2 diabetes. For example, patients with type 1 diabetes, which is mostly an autoimmune disorder, are more likely to develop other autoimmune disorders such as chronic lymphocytic thyroiditis, pernicious anemia, and celiac disease- not so for patients with type 2 diabetes. Also, if a patient has clinical features suggesting both types 1 and 2, certain medications used exclusively in patient with type 2 diabetes might be of benefit (along with insulin). If, in the future medications are developed that can target directly the genetic defect or defects in patients with type 2 diabetes, it would be nice to know that the patient has type 2 diabetes (here I’m thinking about the insulin resistance over and above that due to the obesity, and the tendency for the insulin deficiency in patients with thype 2 diabetes to be progressive).

A case history

So here’s a real case of mine to demonstrate the complexities involved in determining whether a patient has type 1 or type 2 diabetes. The patient is a 22 year old male of Hispanic background who presented with a two-week history excessive thirst and urination and a 20 pound weight loss. The patient had been overweight, particularly after he was treated with an atypical antipsychotic medication for 2 months which was stopped about 3 months earlier. The initial laboratory tests showed typical findings for type 1 diabetes- plasma glucose 350 mg/dl, hemoglobin A1c 8.6% (the test that is an index of the blood gluocse level over the previous 3-4 months- normal is <6%), urine ketones were “strongly positive” (typically, urinary ketones which are at breakdown products, are found only in type 1 diabetes). Tests for islet-cell antibodies were negative.

The patient was treated for typical type 1 diabetes and responded well to insulin injections. Over time, the patient did well with his diabetes and hemoglobin A1c levels were always close to the normal range. The patient’s insulin requirements were lower than typical for age and weight; after 7 years of diabetes, the insulin dose had remained very low and hemoglobin A1c close to normal. His weight had remained fairly stable (within 2 weeks of initiation of therapy, the patient regained about half of the weight he had lost just prior to diagnosis.

As the treating physician (to be distinguished from a “medical expert”), I was recently asked by both a plaintiff attorney and a pharmaceutical company defense attorney if I thought the patient had type 1 or type 2 diabetes. My answer was “I don’t know.” At present, the patient has some clinical features that suggest type 2 diabetes; he is somewhat overweight, he has acanthosis nigricans (a skin condition associated with insulin resistance), and he is being managed with a very low dose of insulin (this is according to the attorneys since I have not been treating this patient for several years). The question the attorneys have is whether I thought the patient might have developed type 2 diabetes from the atypical antipsychotic medication he took prior to his diagnosis with diabetes. I have told both attorneys that I didn’t know but that the patient presented with typical type 1 diabetes. In fact, a history of weight loss prior to diagnosis, which was well documented in this patient, would have been more or less unheard of in a patient with type 2 diabetes- with weight loss, patients with type 2 diabetes become less insulin resistant and have lower blood sugar levels and fewer diabetes-type symptoms such as excessive thirst and urination. On the other hand, the patient’s present clinical status is much more typical of type 2 than tye 1 diabetes. The “negative” test for islet-cell antibodies at the time of diagnosis doesn’t help much- the test is not a great one and some cases of type 1 diabetes are not on a well demonstrated autoimmune basis, although most are. So, what do you think?

One final note- these days, treating the patient discussed above is much easier than answering the various legal questions. Does that mean it’s easier to be a doctor than a lawyer?

When I was in college, I spent a semester living with a family in Dijon, France. No one in the family spoke any English, except an elderly aunt who knew a few phrases. She worked hard to cure me of my American habits, particularly the way I ate. At almost every meal, she would tell me “not so quickly darling,” presumably referring to my tendency to eat faster than was considered appropriate for a Frenchman (you must imagine the order being given with a thick French accent). I am not certain that the eating skills training I got in France have resulted in my eating more slowly these days, but I will never forget my French aunt’s efforts to civilize me.

What’s Your Point Dr. Goldstein?

Recently there have been a number of news reports about two medical studies. The first was about a month ago and showed that patients with established heart disease seemed to develop more heart blood vessel damage on a combination of cholesterol-lowering drugs than on a single drug, despite the combination treatment resulting in a lower cholesterol than the single drug. The other study looked at the development of heart disease in patients with type 2 diabetes and found that patients with the “best” blood sugar control developed more heart disease than those with only “ok” blood sugar control. I don’t want to get deep into the details, but blood sugar control was assessed by measurements of hemoglobin A1c, a well-established test that is an index of average blood glucose levels over the preceding 3-4 months. The study design was to push for normal blood sugar levels in one group of patients but just slightly higher than normal in the second group- a level currently recommend by most expert groups.

The results of these two studies were more or less completely unexpected by the experts who, for the most part, seemed to be scratching their heads but were unwilling to make immediate sweeping recommendations for changes in the treatment guidelines for heart disease and type 2 diabetes patients.

Enter The News Media

One reason most experts were unwilling to change treatment guidelines based on the studies was that the data were inconclusive and puzzling. The cholesterol study was rather small and didn’t look at any “hard” endpoints (e.g., heart attacks, deaths), just lab test numbers and radiologic data. The diabetes study was fairly good sized but the number of events (heat attacks, deaths) were relatively small. Yet the media and a small number of medical “experts” bombarded us with the news that the studies had “turned conventional medical thinking on its head,” and that current therapies for diabetes and heart disease are being rethought. I have had these studies (actually the news reports about the studies) quoted to me by many of my patients the past few weeks. It’s driving me nearly crazy.

Not So Quickly Darling

I do not believe that the two studies in question (I’m not even going to give you the references to the studies unless you beg me to, since I present the studies only to make a point) ) provide enough information that would compel physicians to change their approach to managing either hyperlipidemia or diabetes mellitus. More and more I see the medical profession “jumping” to conclusions based on this or that medical report which often turns out to be of dubious value. It’s not always that the data are invalid but that the conclusions by the study authors and/or the medical community are incorrect. We need to slow it down some; we shouldn’t ignore new and potentially important scientific findings but rather, try to understand the study design, its conclusions, and whether more data are needed to establish the validity and general applicability of the findings. Just because we hear about something on CNN or NPR or read about it in the New York Times or the Wall Street Journal, doesn’t mean it is true.

Medical science is full of examples of study results that at first glance seemed to be “bombshells,” but later turned out to be duds. Even the opposite is true- studies that failed to show something or other but which were later disproven (this is the case with the hemoglobin A1c test- one of these days I’ll discuss its interesting history).