Decoding MODY -The lesser known form of Diabetes

What does this mean considering every human’s physiological make-up is distinct? A lesser-known and understood the fact about Diabetes is that there are four types of Diabetes. We know of the three prominent ones-Type 1, Type 2 and Gestational but the fourth one- ‘Monogenic Diabetes’ is what attributes to a small number of people living with Type 2 Diabetes but its impact is a significant one!

One of the common misconceptions is using a blanket treatment mechanism for Type 2 Diabetes, not taking into account the possibility of a monogenic form of diabetes. In India, its prevalence currently accounts for about 2-5 per cent of Type 2 diabetes patients who are less than 35 years of age. In the European population, its prevalence is 100 in every million and it affects 1– 5 per cent of diabetes people in the USA and other industrialized countries.

A monogenic form of Diabetes is caused due to a single gene mutation. The most notable are Neonatal Diabetes Mellitus (NDM) and Maturity-Onset Diabetes of the Young (MODY). While NDM occurs in newborns and infants, MODY occurs in children and adolescents and both are often misdiagnosed with Type 1 or Type 2 diabetes. Such forms of Diabetes can only be diagnosed with genetic testing appropriately that can also accurately determine the base of treatment.

MODY is a form of diabetes which is very rare. It runs in families and is caused by a single gene mutation but can occur in 14 different forms - each with its own unique clinical characteristics. The signs and symptoms of MODY are like those of Type 1 or 2 diabetes like high blood sugar levels, feeling thirsty, frequent urination, weight loss etc. People with a family history of diabetes, and children or young people with diabetes or hyperglycaemia should opt for genetic testing, basis which MODY can be detected.

The foremost significance of diagnosing monogenic forms of diabetes like MODY is that unless a correct diagnosis is made, patients can be suspected to have type 1 diabetes and advised to have unnecessary lifelong insulin injections. Take the case of Master Ravi (name changed) who presented with clinical indication of mildly elevated levels of fasting blood sugar, decreased levels of postprandial glucose and his GAD test was negative. There was a family history of diabetes mellitus in his father, paternal uncle and aunt, paternal grandfather and maternal uncle.

Master Ravi was suspected to be affected with diabetes mellitus type-1 but the doctor decided to try genetic testing to confirm this. His genetic test results came negative to Type 1 Diabetes but instead, it showed a novel mutation to a gene PDX1 associated with Maturity Onset Diabetes in Young (MODY). MODY is an autosomal dominant form of diabetes typically occurring before 25 years of age and caused by primary insulin secretion defects. Despite its low prevalence, MODY is not a single entity but represents genetic, metabolic, and clinical variations. In some cases, mutations in this gene may confer susceptibility to diabetes mellitus type-II.

Based on the findings of his genetic test his treatment and management pattern could alter to suit somebody with Type II diabetes which involved oral diabetic drugs instead of Type I diabetes which involved regular insulin injections and associated monitoring. Genetic testing was also recommended for his immediate family so that the novel mutation seen in his test is characterised.

Diabetes is not a disease and can be easily managed provided its root causes are clear and enables the treating doctor to chart out the right course of treatment. A patient living on Insulin injections may have MODY which can be managed and treated with a simple and cheap prescription of ‘Sulphonylurea’ tablet which has been used for decades in treating diabetes. This clearly reflects that right understanding of the disease and awareness about a monogenic form of diabetes can be a dramatic change as far as the treatment and the life of such patients are concerned.

Genetic testing in Diabetes can be a life-changer for patients who depend upon costly Insulin treatments. Having witnessed the advantage of genetic tests in decoding healthcare problems and concerns such as cancer, rare diseases, reproductive health or infectious diseases like tuberculosis, Indian is warming up to genetic analysis. But the tool needs a lot of awareness, trust and research to be able to mainstream its impact. Awareness about all aspects of every disease especially Diabetes which is the most prevalent lifestyle disease today in the country is important. A slight treatment modification based upon the actual cause of a disease can help prove to be a great deal of inappropriate management and improving one’s quality of life!

Dr Srinivasan Vedantam

Guest Author The author is Associate Director, Lab operations at MedGenome Labs.