Diabetes is undeniably one of the world’s most common chronic non-communicable disease. Despite that, maturity-onset diabetes of the young (MODY) – a type of diabetes frequently misclassified – remains an infrequently heard of entity.

MODY: A monogenic form of diabetes affecting adolescents and young adults

MODY is a distinct type of diabetes that is often diagnosed in those younger than 25 years of age. It is an autosomal dominant monogenic disease that manifests in the presence of specific genetic mutations. These mutations result in either increased insulin resistance or severe impairment in insulin production by affecting pancreatic beta-cell function1.

Over 20 types of genes have been found to be strongly associated to MODY – with HNF1A, glucokinase, HNF1B, HNF4A, IPF1 and NEUROD1 accounting for 87% of all MODY in the United Kingdom2. The discovery of the RFX6 gene mutation adds to the growing list of MODY associated genes. Interestingly, the authors documented for the first time a reduced secretion of gastric inhibitory polypeptide (GIP), a hormone intricately involved in insulin regulation3.

Maturity onset diabetes of the young has strong genetic associations. Photo credit: KTPH
Maturity onset diabetes of the young has strong genetic associations. Photo credit: KTPH

This discovery highlights the complexity of MODY and the need for further research. However, MODY is an extremely uncommon condition. Studies estimate that it makes up less than 2% of all types of diabetes. Given its rarity, it is unsurprising that most patients with MODY are misdiagnosed as having type 1 or type 2 diabetes4. Furthermore, MODY can only be identified with specialised genetic testing that is costly and not widely available.

Nevertheless, distinguishing MODY from other forms of diabetes goes beyond simply fulfilling clinical curiosity. Patients with different types of MODY have been found to be responsive to specific types of anti-diabetic therapy. For example, not all patients require insulin – as documented in a case report of a 50-year-old woman with MODY in Singapore that was misdiagnosed with type 1 diabetes. Despite receiving insulin for over 30 years, she managed to be weaned off insulin completely after her revised diagnosis5.

A UK study reports that there is a delay of 12 years between being first diagnosed with diabetes to being accurately diagnosed with MODY4.

Model of a pancreatic beta cell and the proteins implicated in maturity onset diabetes of the young (MODY). Photo credit: Fajans SS, Bell GI, Polonsky KS/The University of Chicago Medicine
Model of a pancreatic beta cell and the proteins implicated in maturity onset diabetes of the young (MODY). Photo credit: Fajans SS, Bell GI, Polonsky KS/The University of Chicago Medicine

KTPH MODY registry hopes to increase understanding and awareness of the disease

Prompt recognition of MODY enables optimal patient management and avoids years of unnecessary treatment. In efforts to increase awareness of the condition, physicians and scientists from Khoo Teck Puat Hospital (KTPH) in Singapore have initiated the formation of a MODY registry. Singapore is home to an estimated 2,500 to 5,000 people with MODY, with one in nine Singaporeans living with diabetes6.

Officially launched in April 2017, the registry already consists of 35 people. It is hoped that this registry will help optimise patient management. Genetic testing and counseling can also be offered to patients’ family members.

“We have this very niche subset population who have very special needs, which requires very specific treatments, which means that the right patient is given the right treatment at the right time," expresses Associate Professor Lim Su Chi, a senior consultant at the diabetes centre of KTPH6.

The KTPH registry lists the following scenarios where MODY may be possible7:

• A diagnosis of diabetes younger than 25 years of age

• A diagnosis of type 2 diabetes in the absence of obesity

• Longstanding type 2 diabetes that is well controlled with diet alone

• Strong family history of diabetes that is present in more than 2 generations

The Singapore General Hospital (SGH) and the National University Hospital (NUH) of Singapore are two other hospitals that test for MODY. The former has its own MODY database that started in 2013, with about 30 patients in it. In hopes to expand its database nationwide, SGH is open to future collaboration with KTPH6. MIMS

Read more:
Gene therapy may reduce the burden of diabetes
War on diabetes: Preventing the onset of diabetes – Part 1
War on diabetes: Early screening and prevention – Part 2

Sources:
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570381/
2. http://www.diabetesgenes.org/content/maturity-onset-diabetes-young
3. http://www.cardiovascularbusiness.com/topics/lipid-metabolic/scientists-discover-new-form-diabetes-caused-gene-mutation
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696982/
5. https://www.omicsonline.org/open-access/cessation-of-multiple-daily-insulin-injections-in-a-person-with-twentynineyears-of-type-1-diabetes.php?aid=87143&view=mobile
6. http://www.straitstimes.com/singapore/health/patients-with-rare-diabetes-tracked-with-new-registry?login=true
7. https://www.ktph.com.sg/cru/section_page/516