MDRF & US Scientists Discover New Di abet es Subtype: A Global Breakthrough in MOD Y Research
Newly identified genetic mechanism co uld revolutionize diagnosis and treatment of M aturity-Onset Diabetes of the Young (MOD Y).
Chennai, 8th May, 2025: In a major break th hrough, researchers from the Madras Diabe tes Research Foundation (MDR F) in Chenn ai, India, and Washington Un iversity School of Medicine in St. Louis, Missouri, USA ha ve jointly announced t he discovery of a ne w subtype of MODY diabetes, potentially tra nsforming how certain forms of the disease are diagnosed and treated worldwide. The d iscover y centers around a rare, inherited f orm of diabetes called Maturity-Onset Diab etes of the Young (MODY), a genetic form o f diabetes typically diagnosed in childhood and adolescence and has been published o nline ahead of print in the prestigious journ al ‘Diabetes’, published b y the American Di abetes Association.
The study, based on a collaborative invetig ation involving detailed genetic and functio nal analyses of Indian patients clinically dia gnosed with MODY, reveals a groundbreakin g ing mechanism behind a subtype of MOD Y affecting the ABCC8 ge ne which plays a crucial role in pancreat ic β cell function.
Prof Colin G Nichols, the lead researcher of this work from Washington University Scho ol of Medicine, St Louis, Missouri, USA stat es: “Usually ABCC8 mutati ons work throug h Gain Of Function (GOF) mutations which lead to enhanced AB CC8 protein activity. T his can occur in neonatal period when it is known as Neo natal Diabetes. In adults it o ccurs as AB CC8 MODY or MODY 12). Thro ugh our collaborative work with MDRF, usin g various experiments in the laboratory, w e were able to show some novel mutati ons in the Indian patients with MODY which occur as Loss Of Function (LOF). LO F mutations, abolish or reduce the activity of protein and they normally lead to Congenital Hyperinsu linism (CHI) which p resents as persistent l ow blood glucose levels (hypoglycemia) in childhood. Thes se patients seem to have had CHI earlier but crossed over to the opp osite condition, of high blood sugar (diabet es) in late r life. This is the first demonstrati on of t his mechanism in a MODY subtype t o our knowledge”.
Dr. Radha Venkatesan, Executive Scientific Officer and Head of Molecular Gene tics, w ho is the lead researcher of this w ork from MDRF, emphasizes the import ance of the w ork and states, “This disco very of novel ge netic subtype of MODY represents a signifi cant advancement in our understanding of MODY and explai ns the function of potass ium ATP (K-AT P) channels in the pancreat atic beta cell membrane. Through our work in the lab a nd follow-up of our patients, we propos e that diabetes driven by KATP-Gain of Function and KATP-Loss Of Function m utations should be officially be recognized as distinct disease subtypes, with di fferent molecular basis and different clininical and therapeutic imffplications”.
Dr. V. Mohan, Chairman of MDRF adds, “We are excited that we have discovered a new sub type of MODY diabetes. Thi s work und erscores the importance of genetic testing and functional understanding for precision diagnosis of diabetes i n particular and MO DY subtypes of diab etes in particular. By id entifying these u nique subtypes of MODY, we are close t o providing more precise dia gnosis, treatment and better care for indivi duals af fected by this novel subtype of M ODY.
Patients with this new (Loss of Function) M ODY subtype do not respond to Sulph onlyu onylureas unlike other forms of MODY like MODY 3 & MODY 1 & MODY 12. Further stu dies are needed to assess th e best antidia betic medicines to treat th is novel type of diabetes. This study also opens up new ave nues for discovery of novel drug targets in diabetes treatment”.
MODY is a rare, inherited form of diabetes caused by mutations in a single gene, typia lly presenting in adolescents and young adu lts. While 13 MODY subtypes have been rec ognized so far, this newly identified variant upends long-standing assumptions about h ow the disease dev elops. The discovery no t only expands t he scientific understanding of MODY bu t also underscores the urgent n eed for w ider access to genetic screening — partic ularly in countries like India, where such testing is not yet part of routine diabet etes care. This breakthrough could mark a turning point in advancing personalized dia gnosis, treatment, and long-term managem ment for thousands of individuals li ving wit h undetected or misclassified fo rms of dia betes.
About Madras Diabetes Research Foun dati on (MDRF): Founded in 1996 by Dr. V. Moha n, the Madras Diabetes Researc h Foundati on (MDRF) is one of India’s premier instituti ons dedicated to diabetes and metabolic re search. Recognized as a n ICMR Collaborat ing Centre of Excelle lence, MDRF focuses on high-impact re search spanning epidemi ology, genomic ics, clinical trials, nutrition and public he alth. With over 1,800 scientif ic publicat ions in reputed journals and coll aborati ons with leading global institutions and universities, MDRF continues to play a v ital role in shaping evidence-based strat te gies for the prevention and managem ent of diabetes in India and globally.