NEW DELHI: In a breakthrough, Indian and US researchers have jointly announced the discovery of a new subtype of Maturity-Onset Diabetes of the Young (MODY) a group of inherited forms of diabetes characterised by high blood sugar levels, often diagnosed before the age of 30.
The researchers from the Madras Diabetes Research Foundation (MDRF) in Chennai and Washington University School of Medicine in St. Louis, Missouri, USA, stated that this global breakthrough in MODY research has the potential to transform how certain forms of the disease are diagnosed and treated.
The discovery centres around a rare, inherited form of diabetes known as MODY a genetic form of the disease typically diagnosed in childhood or adolescence. According to the researchers, this finding could revolutionise the diagnosis and treatment of MODY, which is distinct from the more common Type 1 and Type 2 diabetes.
Dr V. Mohan, Chairman of MDRF one of India’s premier institutions dedicated to diabetes and metabolic research said, “We are excited that we have discovered a new subtype of MODY diabetes.”
“This work underscores the importance of genetic testing and functional understanding for the precise diagnosis of diabetes in general, and MODY subtypes in particular,” he added.
He told this paper that it is clear not everyone has Type 1 or Type 2 diabetes, contrary to widespread belief. “One should be on the lookout for rarer forms of diabetes, as this is part of precision medicine. Only a precise diagnosis can lead to precise therapy.”
While the prevalence of this new subtype in India is not yet known, Dr Mohan noted that MODY itself accounts for only 2–3% of all diabetes cases.
He also highlighted that there are more than 50 different types of diabetes. “Type 1 and Type 2 diabetes are the most common, followed by gestational diabetes. But there are many other genetic forms, such as neonatal diabetes, MODY, diabetes secondary to chronic pancreatitis, drug-induced diabetes, etc.”
To date, 13 MODY subtypes have been recognised. This newly identified variant challenges long-standing assumptions about how the disease develops and significantly expands scientific understanding of MODY. It also underscores the urgent need for broader access to genetic screening particularly in countries like India, where such testing is not yet standard practice in diabetes care.
“This breakthrough could mark a turning point in advancing personalised diagnosis, treatment, and long-term management for thousands of individuals living with undetected or misclassified forms of diabetes,” Dr Mohan said.
“By identifying these unique subtypes of MODY, we are moving closer to providing more precise diagnosis, treatment, and better care for individuals affected by this novel MODY subtype. Patients with this new Loss-of-Function (LOF) MODY subtype do not respond to sulphonylureas, unlike other MODY types such as MODY 1, 3, and 12. Further studies are needed to determine the most effective antidiabetic medications for treating this new form. This study also opens new avenues for discovering novel drug targets in diabetes treatment,” he added.
The research, based on a collaborative investigation involving detailed genetic and functional analyses of Indian patients diagnosed with MODY, reveals a groundbreaking mechanism behind a subtype involving the ABCC8 gene, which plays a crucial role in pancreatic β-cell function.
Professor Colin G. Nichols, the lead researcher from Washington University School of Medicine, said: “Usually, ABCC8 mutations act through Gain-of-Function (GOF) changes, which enhance ABCC8 protein activity.”
“This can present in the neonatal period as Neonatal Diabetes. In adults, it appears as ABCC8 MODY or MODY 12. Through our collaboration with MDRF, and using various laboratory experiments, we identified novel mutations in Indian patients with MODY that act as Loss-of-Function (LOF),” he said.
“LOF mutations abolish or reduce protein activity and are typically associated with Congenital Hyperinsulinism (CHI), which manifests as persistent hypoglycaemia in childhood. These patients appear to have had CHI earlier in life, but later transitioned to the opposite condition diabetes. To our knowledge, this is the first demonstration of such a mechanism in a MODY subtype,” he added.
Dr Radha Venkatesan, Executive Scientific Officer and Head of Molecular Genetics at MDRF an Indian Council of Medical Research (ICMR) Centre of Excellence said, “This discovery of a novel genetic subtype of MODY represents a significant advancement in our understanding and sheds light on the function of potassium ATP (K-ATP) channels in pancreatic beta-cell membranes.”
“Through our laboratory work and patient follow-up, we propose that diabetes driven by KATP Gain-of-Function and KATP Loss-of-Function mutations should be officially recognised as distinct disease subtypes, given their differing molecular mechanisms and clinical and therapeutic implications,” she said.