● Newly identified genetic mechanism could revolutionize diagnosis and
treatment of Maturity-Onset Diabetes of the Young (MODY).
Chennai, 8 th May, 2025: In a major breakthrough, researchers from the Madras Diabetes Research
Foundation (MDRF) in Chennai, India, and Washington University School of Medicine in St. Louis,
Missouri, USA have jointly announced the discovery of a new subtype of MODY diabetes,
potentially transforming how certain forms of the disease are diagnosed and treated worldwide.
The discovery centers around a rare, inherited form of diabetes called Maturity-Onset Diabetes of
the Young (MODY), a genetic form of diabetes typically diagnosed in childhood and adolescence
and has been published online ahead of print in the prestigious journal ‘Diabetes’, published by the
American Diabetes Association.
The study, based on a collaborative investigation involving detailed genetic and functional analyses
of Indian patients clinically diagnosed with MODY, reveals a groundbreaking mechanism behind a
subtype of MODY affecting the ABCC8 gene which plays a crucial role in pancreatic β cell function.
Prof Colin G Nichols, the lead researcher of this work from Washington University School of
Medicine, St Louis, Missouri, USA states: “Usually ABCC8 mutations work through Gain Of Function
(GOF) mutations which lead to enhanced ABCC8 protein activity. This can occur in neonatal period
when it is known as Neonatal Diabetes. In adults it occurs as ABCC8 MODY or MODY 12). Through
our collaborative work with MDRF, using various experiments in the laboratory, we were able to
show some novel mutations in the Indian patients with MODY which occur as Loss Of Function
(LOF). LOF mutations, abolish or reduce the activity of protein and they normally lead to Congenital
Hyperinsulinism (CHI) which presents as persistent low blood glucose levels (hypoglycemia) in
childhood. These patients seem to have had CHI earlier but crossed over to the opposite condition,
of high blood sugar (diabetes) in later life. This is the first demonstration of this mechanism in a
MODY subtype to our knowledge”.
Dr. Radha Venkatesan, Executive Scientific Officer and Head of Molecular Genetics, who is the
lead researcher of this work from MDRF, emphasizes the importance of the work and states, “This
discovery of novel genetic subtype of MODY represents a significant advancement in our
understanding of MODY and explains the function of potassium ATP (K-ATP) channels in the
pancreatic beta cell membrane. Through our work in the lab and follow-up of our patients, we
propose that diabetes driven by K ATP -Gain of Function and K ATP -Loss Of Function mutations should be
officially be recognized as distinct disease subtypes, with different molecular basis and different
clinical and therapeutic implications”.
Dr. V. Mohan, Chairman of MDRF adds, “We are excited that we have discovered a new sub type
of MODY diabetes. This work underscores the importance of genetic testing and functional
understanding for precision diagnosis of diabetes in particular and MODY subtypes of diabetes in
particular. By identifying these unique subtypes of MODY, we are close to providing more precise
diagnosis, treatment and better care for individuals affected by this novel subtype of MODY.
Patients with this new (Loss of Function) MODY subtype do not respond to Sulphonylureas unlike
other forms of MODY like MODY 3 & MODY 1 & MODY 12. Further studies are needed to assess the
best antidiabetic medicines to treat this novel type of diabetes. This study also opens up new
avenues for discovery of novel drug targets in diabetes treatment”.
MODY is a rare, inherited form of diabetes caused by mutations in a single gene, typically
presenting in adolescents and young adults. While 13 MODY subtypes have been recognized so far,
this newly identified variant upends long-standing assumptions about how the disease develops.
The discovery not only expands the scientific understanding of MODY but also underscores the
urgent need for wider access to genetic screening — particularly in countries like India, where such
testing is not yet part of routine diabetes care. This breakthrough could mark a turning point in
advancing personalized diagnosis, treatment, and long-term management for thousands of
individuals living with undetected or misclassified forms of diabetes.
