Five Types of Diabetes: Will New Classification Make Management Easier?

Jay H. Shubrook, DO; Sumera Ahmed, MD

Disclosures

June 21, 2018

Jay H. Shubrook, DO: Hi. I am Jay Shubrook, diabetologist and professor at Touro University College of Osteopathic Medicine in California. We are continuing our series, Everyday Diabetes: Practical Management for Primary Care.

Today, Dr Sumera Ahmed joins us. Dr Ahmed is an internist and diabetologist who is a new faculty member at Touro University California. Dr Ahmed, I want to talk a bit about types of diabetes. I believe that people think of type 1 and type 2, but there are actually several more types of diabetes. Could you tell the audience how you see the general groups of diabetes?

Sumera Ahmed, MD: The common, very broad classifications we traditionally think of are type 1 and type 2 diabetes. As we all know, type 1 diabetes is usually characterized by autoimmunity and absolute insulin deficiency. Patients with type 1 diabetes are insulin dependent and very insulin sensitive. They characteristically have a low body mass index (BMI) and are very carbohydrate sensitive.

Patients with type 2 diabetes have insulin resistance or a related insulin deficiency over a prolonged period of time. Patients with type 2 diabetes typically have a higher BMI and features of insulin resistance, such as acanthosis nigricans. They also have a strong family history of diabetes.

There are other diabetes types. Nowadays, we see atypical diabetes, such as ketosis-prone diabetes, formerly called Flatbush diabetes. We also see latent autoimmune diabetes of adult onset (LADA) and other subtypes under the broad classifications of type 1 and type 2 diabetes.

Shubrook: And, of course, gestational diabetes is also quite common and closely associated with type 2. Research by investigators from Lund University in Sweden, recently published in The Lancet Diabetes and Endocrinology, proposed a new classification system.[1] Tell me about this.

Ahmed: This study was conducted with a Scandinavian cohort. Patients with diabetes were categorized into five clusters, based on the severity of diabetes. Patients with severe diabetes were placed in the first three clusters, and those with milder diabetes were placed in clusters 4 and 5. The first cluster comprises severe autoimmune diabetes. Here is included the typical patient with type 1 diabetes, with severe insulin deficiency secondary to autoimmunity. These patients were insulin dependent and required insulin to survive. They also had very low BMIs.

Patients in cluster 2 also had severe insulin deficiency, but without evidence of autoimmunity. These patients had low BMIs and required insulin injections to survive.

Cluster 3 is severe insulin-resistant diabetes; in addition, these patients had the typical metabolic or physical features of what we currently call type 2 diabetes—they had higher BMIs and severe insulin resistance; hence, they were also insulin dependent. These patients had a high propensity for chronic diabetic nephropathy, in contrast to patients with severe insulin-deficient diabetes, who had a high propensity for retinopathy. That was a difference that the investigators noticed in these cohorts.

Clusters 4 and 5 are the milder forms of diabetes; cluster 4 is obesity-related diabetes and cluster 5 is the mild, age-related diabetes. Cluster 4 patients had higher BMIs, but they did not exhibit the high insulin resistance that was seen in the cluster 3 patients. Cluster 5 patients had a milder form of diabetes, with the onset at an older age.

Thus, the five clusters were based on severity, the presence of GAD (glutamic acid decarboxylase) antibodies, HbA1c, and the presence of insulin and beta-cell function.

Why Does New Classification Matter?

Shubrook: This study looked at a known population of patients with diabetes to tease out the different types. Why is this important?

Ahmed: I believe they felt that it helped to individualize the treatment plan; they could personalize the treatment based on the patient’s classification. For example, if patients had severe insulin resistance and thus were perhaps more prone to develop diabetic nephropathy, could the treatment plan be personalized to account for that? In my opinion, this classification is more clinically and practically useful.

Shubrook: As you have described these clusters, type 1 is cluster 1; type 1B or LADA could be included in cluster 2; cluster 3 is classic insulin resistance; cluster 4 is probably an emerging type where people have not so much the genetics of insulin resistance but obesity-related type 2 diabetes. Cluster 5 is what I would call "old-fashioned diabetes." Some of us have been in practice long enough to remember when some people had a very indolent course of diabetes in their 80s. It was not a bad disease, and it probably needs to be treated differently.

Ahmed: It is interesting that you say that. As a hospitalist, I also see many patients for whom we may not have access to medical records. When you ask the patients about type of diabetes, those taking insulin will often say that they have type 1, when in fact they actually have an advanced type 2 diabetes or a prolonged period of type 2 diabetes and now require insulin.

My dad was diagnosed with diabetes when he was much older, over 65 years of age, and he did not have a higher BMI. He has type 2 diabetes with a strong family history, but I always wondered, where do I place him? Now I have the answer. I can place him into cluster 5. He has mild age-related diabetes, with an indolent course. He is doing great on metformin.

I love this new classification. It will help me categorize my patients more easily and will help me individualize the treatment.

Shubrook: So you are a proponent for a new classification.

Ahmed: Yes, absolutely.

Shubrook: The researchers also highlighted the finding that many people in cluster 3 were not receiving metformin, and this is probably one of the most important groups to get it. This brings us back to your focus of giving the right treatment to the right people.

Ahmed: Yes. If patients in cluster 2 have a high risk for retinopathy and patients in cluster 3 have a high risk for nephropathy, we need to make sure that they are screened appropriately. Of course, patients with diabetes do need all of their screenings, but perhaps this helps us focus on patients in these two clusters, to make sure that they get the appropriate screenings and follow-up care.

Shubrook: I very much appreciate your insights. I have learned something from this. For our listeners, stay tuned because there may be a new classification coming. Thank you very much.

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