Diabetes Mellitus endodoc on 11 Apr 2008 01:04 pm
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.
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.Â 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?