Idiopathic Type 1 Diabetes in Dallas

In this issue of Diabetes Care, the letter by Bennett et al. (1) in response to our study (2) points out a huge problem that we wished to previously identify. The problem is “the importance of a name” (3). Dr. Bennett and his colleagues (1), who are respected epidemiologists, considered our study subjects to have type 2 diabetes, whereas we determined that they met the diagnostic criteria for idiopathic type 1 diabetes.

According to the report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (4), idiopathic type 1 diabetes is described as follows: “This form of diabetes is strongly inherited, lacks immunological evidence for β-cell autoimmunity, and is not HLA associated. An absolute requirement for insulin replacement therapy in affected patients may come and go.” Even in “typical” type 1 diabetes, the absolute requirement for insulin “to preserve life” is not always 100%, especially early in the course of the illness. This so-called “honeymoon period” is probably longer for individuals with idiopathic type 1 diabetes. We strongly feel that our patients have idiopathic type 1 diabetes. They all presented with unprovoked ketoacidosis and had none of the associated HLA haplotypes or markers of β-cell autoimmunity commonly seen in individuals with immune-mediated type 1 diabetes. All had a strong family history for what is called type 2 diabetes. In sum, all of these components meet the diagnostic criteria for idiopathic type 1 diabetes. Decisions on the classification for each individual with diabetes must be clinical and are often difficult.

We also disagree with the statement by Bennett et al. (1) that “[i]t is well established that adolescents and young adults with type 2 diabetes often develop ketoacidosis, which may be the event that leads to diagnosis.” The study by Umpierrez et al. (5), which they used in support of this statement, actually describes individuals with idiopathic type 1 diabetes. With respect to the report by Wilson et al. (6) in Apache Indians, we may have been incorrect in including such patients as examples of idiopathic type 1 diabetes. It is difficult to tell from reading the article (6) exactly how many of those patients developed ketoacidosis in the absence of any precipitating factor (infection, alcohol, etc). There is no question that developing ketoacidosis in association with external stressors, such as infection or alcohol abuse, is not unusual in type 2 diabetes, and we have no argument with that statement. It is interesting to note that we had three Native Americans in our study population, so it is possible that some of the patients described by Wilson et al. (6) actually did have idiopathic type 1 diabetes.

It is our belief that idiopathic type 1 diabetes is very common in minority populations in urban areas. What sets this type of diabetes apart from the typical case of type 2 diabetes is the development of spontaneous ketoacidosis. According to the Expert Committee’s report (4), in type 2 diabetes, “Ketoacidosis seldom occurs spontaneously; when seen, it usually arises in association with the stress of another illness such as infection.” All of our subjects presented with ketoacidosis that was not associated with other stressors. As was noted above, that was probably not the case with all of the patients reported by Wilson et al. (6).

The purpose of our study was not to argue over names, although we feel that we are justified in saying that this group of individuals did in fact meet the Expert Committee’s definition of idiopathic type 1 diabetes. More importantly, we wanted to make the clinical recommendation that, when individuals who seem to be at risk for type 2 diabetes (i.e., are older, are obese, and have acanthosis nigricans) present with unprovoked ketosis or ketoacidosis, the appropriate long-term therapy is insulin. What name we attach to such individuals is probably unimportant.