MODY: when diabetes runs in the family because of a single gene

Most diabetes is caused by many genes acting together with lifestyle. MODY is different. It is caused by a change (variant) in one gene that affects how the pancreas senses sugar or makes insulin. It is uncommon, but in families where it runs, getting the diagnosis right can make a real difference to treatment.

How is MODY passed on?

MODY is usually inherited in an autosomal dominant way. This means a parent with the gene change has about a 50% chance of passing it to each child, whether the child is a boy or a girl. That is why families with MODY often have diabetes in every generation: a grandparent, a parent and a child, often diagnosed young.

Not every family history is so clear. Some people with MODY have a new gene change, and some relatives may have been told they have type 1 or type 2 diabetes.

What clues make a doctor suspect MODY?

• diabetes diagnosed young, usually before 30 to 35 years of age
• diabetes in one parent and in several generations
• a normal or low body weight, without the usual signs of insulin resistance
• negative diabetes antibodies, unlike type 1 diabetes
• the body still making its own insulin years after diagnosis (measured by C-peptide)
• no ketones, even when sugar is high
• a long “honeymoon”, or needing very little insulin

It can also be mistaken for type 2 diabetes found on a routine sugar test, or for gestational diabetes when it is first picked up in pregnancy.

Doctors sometimes use an online probability calculator, developed in the UK, to judge how likely MODY is before ordering a genetic test. Indian researchers are developing versions better suited to Indian patients, because young-onset type 2 diabetes is very common here and can look similar.

What are the main types of MODY?

There are more than a dozen genes, but a few account for most cases:

• HNF1A MODY (often called MODY 3). The most common type found in India. Sugar rises gradually from the teens or twenties. People with it are often very sensitive to a group of tablets called sulfonylureas.
• HNF4A MODY (MODY 1). Similar to HNF1A. Babies may be born large or have low sugar after birth.
• GCK MODY (MODY 2). Causes a mild, stable rise in fasting sugar from birth. It usually causes few complications and often needs no treatment outside pregnancy. It is sometimes picked up during pregnancy or a routine check.
• HNF1B MODY (MODY 5). Diabetes together with kidney cysts or kidney malformations, and sometimes genital tract differences.

Other single-gene forms include diabetes with deafness passed through the mother (MIDD) and Wolfram syndrome.

How common is it in India?

A pan-India study published in 2025 tested 774 people from 65 centres who had diabetes before 30, a family history in a parent, a BMI of 30 or less and no ketones. About 15% had a confirmed single-gene cause. HNF1A was the most common, followed by HNF4A and HNF1B. Many had been living with the wrong diagnosis for years.

How is MODY diagnosed?

MODY is confirmed with a genetic test on a blood or saliva sample, usually a panel that looks at all the known MODY genes at once. Your doctor will often check diabetes antibodies and C-peptide first, to decide whether genetic testing is worth doing. Genetic testing is available through several laboratories in India. It is a one-time test, and if a gene change is found, relatives can be tested for that specific change.

Genetic counselling before and after testing helps you understand what the result means for you, your children and your siblings.

Why does the diagnosis matter?

The type of MODY guides treatment:

• In HNF1A and HNF4A MODY, many people are well controlled on a low dose of a sulfonylurea tablet, and some who were on insulin can move off it. Any change like this must be planned and supervised by your doctor, with careful sugar monitoring.
• In GCK MODY, treatment is often not needed, which saves years of unnecessary medicines. Pregnancy needs special planning, because the baby’s growth depends on whether the baby has inherited the gene.
• In HNF1B MODY, insulin is usually needed and the kidneys need regular checks.

A diagnosis also helps relatives. A child or sibling with the same gene change can be watched and treated early.

What should I ask my doctor?

• Do my age at diagnosis, weight and family history fit MODY?
• Should I have antibodies and C-peptide checked first?
• Would a genetic test change my treatment?
• Should my children or siblings be tested?

If MODY seems possible in your family, book a consultation to discuss testing.