Conference Coverage

A starting point for precision medicine in type 1 diabetes


 

– With type 1 diabetes, there can be great differences in terms of epidemiology, genetics, and possible constituent causes, as well as in the course of the disease before and after diagnosis. This point was made evident in the Can We Perform Precision Medicine in T1D? conference.

At the 63rd Congress of the Spanish Society of Endocrinology (SEEN), María José Redondo, MD, PhD, director of research in the division of diabetes and endocrinology at Texas Children’s Hospital Baylor College of Medicine in Houston, noted that delving into this evidence is the “clue” to implementing precision medicine strategies.

“Physiopathologically, there are different forms of type 1 diabetes that must be considered in the therapeutic approach. The objective is to describe this heterogeneity to discover the etiopathogenesis underlying it, so that endotypes can be defined and thus apply precision medicine. This is the paradigm followed by the European Association for the Study of Diabetes (EASD), the American Diabetes Association (ADA), and other organizations,” said Dr. Redondo.

She added that there have been significant advances in knowledge of factors that account for these epidemiologic and genetic variations. “For example, immunological processes appear to be different in children who develop type 1 diabetes at a young age, compared with those who present with the disease later in life.”

Metabolic factors are also involved in the development of type 1 diabetes in adolescents and adults, “and this metabolic heterogeneity is a very important aspect, since we currently use only glucose to diagnose diabetes and especially to classify it as type 1 when other factors should really be measured, such as C-peptide, since it has been seen that people with high levels of this peptide present a process that is closer to type 2 diabetes and have atypical characteristics for type 1 diabetes that are more like type 2 diabetes (obesity, older age, lack of typically genetic factors associated with type 1 diabetes),” noted Dr. Redondo.

Eluding classification

The specialist added that this evidence suggests a need to review the classification of the different types of diabetes. “The current general classification distinguishes type 1 diabetes, type 2 diabetes, gestational diabetes, monogenic (neonatal) diabetes, monogenic diabetes associated with cystic fibrosis, pancreatogenic, steroid-induced, and posttransplantation diabetes. However, in clinical practice, cases that are very difficult to diagnose and classify emerge, such as autoimmune diabetes, type 1 diabetes in people with insulin resistance, positive antibodies for type 2 diabetes, for example, in children with obesity (in which it is not known whether it is type 1 or type 2 diabetes), drug-induced diabetes in cases of insulin resistance, autoimmune type 1 diabetes with persistent C-peptide, or monogenic diabetes in people with obesity.

“Therefore, the current classification does not help to guide prevention or treatment, and the heterogeneity of the pathology is not as clear as we would like. Since, for example, insulin resistance affects both types of diabetes, inflammation exists in both cases, and the genes that give beta cell secretion defects exist in monogenic diabetes and probably in type 2 diabetes as well. It can be argued that type 2 diabetes is like a backdrop to a lot of diabetes that we know of so far and that it interacts with other factors that have happened to the particular person,” said Dr. Redondo.

“Furthermore, it has been shown that metformin can improve insulin resistance and cardiovascular events in patients with type 1 diabetes with obesity. On the other hand, most patients with type 2 diabetes do not need insulin after diagnosis, except for pediatric patients and those with positive antibodies who require insulin quickly. Added to this is the inability to differentiate between responders and nonresponders to immunomodulators in the prevention of type 1 diabetes, all of which highlights that there are pathogenic processes that can appear in different types of diabetes, which is why the current classification leaves out cases that do not clearly fit into a single disease type, while many people with the same diagnosis actually have very different diseases,” she pointed out.

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