Type 1 diabetes is an autoimmune condition in which the patient’s immune system attacks cells that produce insulin. Researchers have achieved recent successes at delaying — and perhaps even altogether preventing — the development of type 1 diabetes. Now, the question is who is at risk of developing type 1 diabetes and should get those preventive treatments.
Previously, clinicians diagnosed type 2 diabetes primarily in adults. Today, pediatric cases have increased sharply, especially among racial and ethnic minorities. However, signs and symptoms of type 1 or type 2 diabetes can overlap. For example, obesity is common in people with type 2 diabetes, but not rare in those with type 1 diabetes.
Often, clinicians are unable to pinpoint a patient’s type of diabetes upon diagnosis. Some patients may even have a blend of types 1 and 2.
Adding to the confusion is a third, lesser-known type of diabetes caused by a single gene: monogenic diabetes.
Other patients have atypical diabetes — a case that clinicians cannot clearly define as type 1, type 2 or monogenic diabetes, or as having any other known cause. The diabetes may resemble a certain type, but does not entirely align. As a result, patients with an unrecognized form of diabetes are at risk of receiving inappropriate treatment.
Diabetes diagnoses in children are increasing steadily — and yet there is much that clinicians still do not understand about this disease.
Different types of diabetes have different treatments, which means that clinicians face the challenges of establishing the correct diagnosis as close to onset as possible and delivering more targeted treatment earlier so that patients can enjoy better outcomes.
It is these challenges that Maria J. Redondo, MD, PhD, MPH — Director of Research in the Division of Diabetes and Endocrinology at Texas Children’s Hospital and Professor of Pediatrics at Baylor College of Medicine — is determined to overcome. Having studied pediatric diabetes since 1997, she aims to expand knowledge of this disease to improve the lives of people with it.
“The wealth of information accumulated on the genetics of diabetes over the past few decades is astounding. The next step is to use that knowledge to answer questions that help us prevent and treat diabetes better,” Dr. Redondo said.
Currently, Dr. Redondo is working on three studies.
The National Institutes of Health (NIH) funds this international, cross-institutional study for which Dr. Redondo serves as the lead principal investigator. The study began in the spring of 2021.
The DISCOVER study examines genetics in combination with islet autoantibodies (markers of the immune system involvement), age, body mass index and other characteristics. Dr. Redondo’s team and their partners at Emory University have recruited 175 children so far, all of whom have a diagnosis of diabetes. Eligible children may participate in the study regardless of whether they were diagnosed recently or have lived with diabetes for several years.
Researchers draw blood samples to evaluate genes, islet autoantibodies and the ability of the patient to make insulin. The detection of islet autoantibodies in blood usually signifies that the immune system has attacked islets, the cells that produce insulin.
Researchers then combine that information along with clinical data and demographic factors to develop a model, or formula, that helps clinicians decide if a person has type 1 or type 2 diabetes at the onset, without having to wait — for years, sometimes — until adverse health events clarify the diagnosis.
For Dr. Redondo and her fellow researchers, racial and ethnic diversity is important for the success of this study.
“Most diabetes studies have focused on people of European origin, but as previous research has shown, the knowledge gained from them does not always apply to other racial and ethnic groups. In DISCOVER, we want to enroll more Hispanic and Black participants to capture a broader cross-section of society,” Dr. Redondo said.
“So far, we have obtained great participation of children and adolescents from racial and ethnic minorities, and we are planning to share our experience with other investigators.”
Dr. Redondo leads another NIH-funded, multicenter research project that seeks to improve prediction of type 1 diabetes by using genetics and other factors. To accomplish this goal, Dr. Redondo and her team are analyzing the genes of participants in a study called Type 1 Diabetes TrialNet.
Launched 25 years ago, TrialNet is open to people who have first-, second-, or third-degree relatives with type 1 diabetes, including parents, children, siblings, grandparents, cousins, aunts and uncles.
Researchers screen participants for the presence of islet autoantibodies, which can be detected in blood years before someone develops type 1 diabetes. Through the years, Dr. Redondo and other investigators have built a model that uses number and type of islet autoantibodies, age, and other factors to estimate someone’s risk of developing type 1 diabetes.
Now, Dr. Redondo and her colleagues are testing how best to incorporate genetic factors into the predictive model. The team’s strategy is to combine nearly 70 of the most important genes that cause type 1 diabetes into a single number, or score, that they can easily integrate into the estimation of probability to develop type 1 diabetes.
“Our goal is to use genetic information for early and accurate prediction of type 1 diabetes. If we know that a person is at risk for this disease, we can take action proactively and prevent approximately one-third of people who develop type 1 diabetes from landing in the intensive care unit,” Dr. Redondo said.
“In addition, we can offer these patients treatments that prevent type 1 diabetes. Preventive treatments currently are available only through clinical trials, but it is highly likely that they will become standard practice in the near future. To assess the risk-to-benefit ratio of prevention treatments, it is critical to have an accurate estimate of the probability that someone will develop type 1 diabetes.”
Maria J. Redondo, MD, PhD, MPH, third from left, and her research team use genetics to better predict, classify and treat diabetes in children.
The NIH-funded RADIANT study focuses on patients whose type of diabetes is unclear. Dr. Redondo, who serves as a site principal investigator, and study principal investigator Ashock Balasubramanyam, MD, Professor of Endocrinology, Diabetes and Metabolism at Baylor, want to help these patients understand the type of diabetes they have.
To accomplish better characterization of unknown diabetes, investigators conduct genetic analysis and other complex tests on participants to gain information on how their bodies handle glucose. A large group of experts in diabetes, genetics, metabolism and related disciplines from all over the U.S. review available data for each case and discuss whether they can make a diagnosis. If not, the group decides which tests they should perform next.
Researchers anticipate that this study will discover new causes of diabetes. Knowing the cause is an important step in obtaining the most effective treatment for this condition, as is currently the case in monogenic diabetes, where genetic testing is standard practice and enables clinicians to switch some patients safely from insulin to tablets.
With the studies described above, Dr. Redondo and her team are using the power of genetics to better classify diabetes in children, predict type 1 diabetes and discover new causes of diabetes. Her studies are helping the medical community reach the point at which genetic testing will be another available tool for early detection and treatment of all types of diabetes.