A Guide to Monogenic Diabetes: Types, Causes

Monogenic Diabetes: Understanding This Rare Genetic Disorder

Monogenic Diabetes

Monogenic diabetes is an uncommon condition caused by changes or mutations in a single gene. Alternatively, the most common types of diabetes, type 1 and type 2, are caused by multiple genes and in type 2 diabetes, ( lifestyle factors like obesity). Many cases of monogenic diabetes are inherited from a parent who also has the disorder. It accounts for two to five percent of all diabetes mellitus.

Monogenic diabetes takes several forms and most frequently affects young people, the majority of whom are 25 years or younger. In many forms of disease, the body is less able to create insulin, a hormone that assists the body in using glucose (sugar) for energy.

The problem is hardly severe insulin resistance, a condition in which the body cannot utilise insulin correctly. Based on when it develops, this particular form of monogenic diabetes may be known as MODY (maturity-onset diabetes of the young) or neonatal diabetes.

Endocrine Connection 

People usually have two copies of most genes, with one gene inherited from each parent. Genes are essential for creating proteins inside the cells. If a gene has mutated, the protein cannot function correctly, impacting the body’s ability to create or regulate insulin properly.

The hormone insulin enables the cells in the muscles, liver and fat to absorb glucose in the blood. The glucose works as energy for these cells otherwise it can be converted into fat when required. Insulin also impacts other metabolic processes, like the breakdown of protein or fat.

Few patients affected by monogenic diabetes are misdiagnosed as having type 1 or 2 diabetes. The genes control the function, development, and regulation of the pancreatic insulin-producing cells. The monogenic diabetes conditions were formerly numbered, linked to the timing of the discovery of the genetic problem; however, they are now referred to by their genetic mutations.

The most common mutations are linked to the hepatocyte nuclear factor alpha (HNF1A, MODY3) and glucokinase ( GCK, MODY 2) genes in 50-60% of people with monogenic diabetes.

Certain genes causing monogenic diabetes can also create a more serious form of diabetes, presenting as a baby (neonatal diabetes). The genes are classified based on whether they create abnormal insulin production and secretion, abnormal pancreas development and islet cell destruction.

Symptoms of Monogenic Diabetes

The symptoms of monogenic diabetes are similar to other types of diabetes.

• Frequent Urination
•  Blurry Vision
• Dehydration
• Recurrent Skin Infections
• Thirst
•  Recurrent Yeast Infections
•  Rapid Breathing

Diagnosis

Genetic testing and blood sugar tests are used to diagnose monogenic diabetes. Genetic testing is done on saliva or blood samples. The DNA from the samples is analysed for changes in the genes that create monogenic diabetes.

Genetic testing is suggested:

When diabetes is diagnosed within the first 6 months of age.

When diabetes is diagnosed in children and young adults, particularly individuals with a strong family history of diabetes, who do not display common features of  type 1, type 2 diabetes (for instance, having  diabetes-linked autoantibodies, obesity and other metabolic features)

A person exhibits stable, mild fasting hyperglycemia, particularly if they do not have obesity.

Treatment of Monogenic Diabetes

MOD treatment depends on the particular genetic mutation that causes the condition. Individuals who have particular forms of MOD and NDM can be treated with sulfnoylureas, an oral diabetes medicine that assists the body in releasing more insulin into the blood.

Others may need insulin injections. Few people with MOD may not need medication and may be able to maintain ideal glycemia (blood sugar levels) via diet and physical activity.

Summary

Monogenic diabetes is a type of diabetes caused by a single genetic abnormality. The prime sub-categories are neonatal and maturity-onset diabetes of the young (MODY).

Monogenic diabetes is a comparatively rare, however important type of diabetes that is frequently misdiagnosed and incorrectly treated in many patients.