A Starting Point for Precision Medicine in Type 1 Diabetes

Carla Nieto Martínez

December 16, 2022

MADRID — 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, Texas, 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 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 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 post-transplantation 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 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.

Toward Precision Diagnostics

"Encapsulating" all these factors is the first step to applying precision medicine in type 1 diabetes, an area, Redondo explained, in which concrete actions are being carried out. "One of these actions is to determine BMI [body mass index], which has been incorporated into the diabetes prediction strategy that we use in clinical trials, since we know that people with a high BMI, along with other factors, clearly have a different risk. Likewise, we've seen that teplizumab could work better in the prevention of type 1 diabetes in individuals with anti-islet antibodies and that people who have the DR4 gene respond better than those who don't have it and that those with the DR3 gene respond worse."

Other recent advances along these lines involve the identification of treatments that can delay or even prevent the development of type 1 diabetes in people with positive antibodies, as well as the development of algorithms and models to predict who will develop the disease, thus placing preventive treatments within reach.

"The objective is to use all available information from each individual to understand the etiology and pathogenesis of the disease at a given moment, knowing that changes occur throughout life, and this also applies to other types of diabetes. The next step is to discover and test pathogenesis-focused therapeutic strategies with the most clinical impact in each patient at any given time," said Redondo.

Technologic Tools

The specialist referred to recent advances in diabetes technology, especially semiclosed systems (such as a sensor/pump) that, in her opinion, have radically changed the control of the disease. "However, the main objective is to make type 1 diabetes preventable or reversible in people who have developed it," she said.

Fernando Gómez-Peralta, MD, PhD, elected coordinator of the Diabetes Department at SEEN and head of the Endocrinology and Nutrition Unit of the General Hospital of Segovia, Spain, spoke about these technologic advances in his presentation, "Technology and Diabetes: Clinical Experiences," which was organized in collaboration with the Spanish Diabetes Society.

According to this expert, technologic and digital tools are changing the daily lives of people with this disease. "Continuous glucose monitoring and new connected insulin pen and cap systems have increased the benefits for users of treatment with new insulins, for example," said Gómez-Peralta.

He explained that most systems make it possible to access complete data regarding glycemic control and the treatment received and to share them with caregivers, professionals, and family members. "Some integrated insulin pump and sensor systems have self-adjusting insulin therapy algorithms that have been shown to greatly increase time-to-target glucose and reduce hypoglycemic events," he said.

"Regarding glucose monitoring, there are devices with a longer duration (up to 2 weeks) and precision that are characterized by easier use for the patient, avoiding the need for calibration, with annoying capillary blood glucose levels."

In the case of insulin administration, it is anticipated that in the future, some models will have very interesting features, Gómez-Peralta said. "Integrated closed-loop glucose sensor and insulin pump systems that have self-adjusting algorithms, regardless of the user, are highly effective and safe, and clearly improve glycemic control.

"For users of insulin injections, connected pens allow the integration of dynamic glucose information with doses, as well as the integration of user support tools for insulin adjustment," Gómez-Peralta added.

The specialist stressed that a challenge for the future is to reduce the digital divide so as to increase the capacity and motivation to access these options. "In the coming years, health systems will have to face significant cost so that these systems are made available to all patients, and it is necessary to provide the systems with more material and human resources so that they can be integrated with our endocrinology and diabetes services and units."

Redondo and Gómez-Peralta have disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish edition.


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