Study Suggests Need for a Precision Approach to Metabolic Diseases

Rare Daily Staff

Monogenic diabetes, a rare form of diabetes caused by a single gene mutation, accounts for 1 to 4 percent of all diabetes cases, but these patients are often confused with type 1 or type 2 diabetes patients. More than 90 percent of these cases are misdiagnosed.

Scientists from the University of Geneva (UNIGE), the University Hospitals of Geneva (HUG), and the Lithuanian University of Health Sciences in Vilnius examined more than 1,200 young patients with diabetes, which allowed them to identify the proportion of monogenic diabetes in the whole pediatric diabetes population.

In doing so, the researchers adjusted treatments according to the genetic characteristics of the disease in order to improve patients’ quality of life. The study, published in the journal Diabetes, highlights the need for precision medicine in the management of metabolic diseases.

Diabetes is defined by chronic hyperglycemia, which may lead to dangerous complications. Type 2 diabetes and type 1 diabetes are the best-known forms. Type 2 diabetes is often associated with obesity, while type 1 is an autoimmune disease where the immune system destroys the insulin-producing pancreatic beta cells. The form of diabetes the researchers studied is called “monogenic,” and is caused by a mutation in a single gene.

The scientists first evaluated the presence of autoimmune antibodies, known markers of type 1 diabetes, in the 1,209 children and young adults included in the cohort. A complete genetic analysis was then carried out on the 153 patients, who did not have these antibodies or who had only anti-insulin antibodies, which can also develop from insulin treatment.

The researchers were able to identify the gene mutation causing diabetes in 42 of the patients. In addition, almost 10 percent of the study participants who tested positive for autoimmune anti-insulin antibodies also had monogenic diabetes.

While most patients had only one defective gene, many different mutations were identified, including eleven genes identified for the first time.

In many gene mutations however, beta cells can be stimulated through specific drugs, called sulfonylureas, which are much easier to administer than insulin injections and which have a much better effect on metabolism. Many of the patients diagnosed were able to switch to a lighter oral treatment, and some even stopped treatment altogether.

The researchers said the study shows the need for precision medicine where treatment is tailored to the causes of the disease, not just the symptoms it triggers.

The researchers have developed a diagnostic test that includes the more than 40 genes that can lead to monogenic diabetes, and all diabetic children, who don’t have autoimmune antibodies can be tested. They said such a test would be useful for adults as well since they are often misdiagnosed as having type 2 diabetes and could benefit from different treatment approaches that could improve their quality of life and reduce costs to the healthcare system.

“Hyperglycemia should therefore be considered as a symptom of various diseases, rather than a disease in itself, and different forms of diabetes should be better screened,” said Valérie Schwitzgebel, lead author of the study, professor at the Department of Paediatrics, Gynaecology and Obstetrics and co-coordinator of the Diabetes Centre of the UNIGE Faculty of Medicine and head of the Paediatric Endocrinology and Diabetology unit at the HUG. “The earlier the actual cause is identified, the sooner appropriate treatments can be initiated, minimizing the risk for long term complications.”