MODY diabetes risk calculator for children and adults

MODY is a form of diabetes usually inherited from a parent, which often goes unnoticed because it resembles type 1 or type 2 diabetes [1] [3]. It is caused by a change in a single gene, and the most common forms involve the GCK, HNF1A and HNF4A genes [3]. It usually appears before age 25, sometimes later, in several generations of the same family [3].

Recognizing MODY matters because the right treatment can be different and often simpler [3]. Outside pregnancy, the GCK form usually needs no treatment, while the HNF1A and HNF4A forms usually respond to sulfonylureas, oral medications [3]. The diagnosis also helps the family, because relatives with diabetes can be tested too [3]. Insulin treatment must not be stopped on your own, only after genetic confirmation, together with your diabetologist.

The percentage shows how likely it is that genetic testing will confirm MODY in a person with the same data as you [1]. The calculator compares your data with those of people with genetically confirmed MODY and with those of people with type 1 or type 2 diabetes [1]. If insulin was started in the first six months after diagnosis, the comparison is with type 1 diabetes, otherwise with type 2 diabetes [1].

What matters most is a parent with diabetes and a lower HbA1c [1]. In people without insulin in the first six months after diagnosis, the age at diagnosis also matters a lot [1]. The probability rises when the age at diagnosis and the body mass index (BMI) are lower [1]. In people treated with insulin from the first six months, the percentages are lower, because type 1 diabetes is much more common than MODY [1]. A percentage above 5%, assessed at least six months after onset, is one of the signs that suggest monogenic diabetes [3].

In a child, MODY can be recognized right from diagnosis, before the first six months of follow-up have passed [2]. The model uses three data from diagnosis: HbA1c, whether a parent has diabetes, and frequent, abundant urination (polyuria) [2]. The probability rises when a parent has diabetes, when HbA1c is lower and when polyuria is absent [2].

HbA1c must be the one from diagnosis, because after treatment starts its value falls and would change the result [2]. The percentage is compared with the average for children newly diagnosed with diabetes, with a decision threshold set at 1.3% [2]. Above this average and with all three pancreatic autoantibodies negative, about one in three children has MODY [2]. The model has been tested on a limited number of children outside the group in which it was built, so it is not fully validated [2].

A high percentage does not make the diagnosis, but it shows that genetic testing is worth discussing with your diabetologist [3]. Only genetic testing confirms MODY [1]. In people treated with insulin, pancreatic autoantibodies and C-peptide are measured first, before genetic testing [3]. Genetic testing is most useful if autoantibodies are absent and C-peptide is above 0.6 ng/mL (200 pmol/L) [3].

A parent with diabetes does not automatically mean MODY, because type 1 diabetes can also occur in several members of the same family [4]. The presence of autoantibodies makes MODY very unlikely [2] [3]. Some signs point to other forms of monogenic diabetes, which the calculator does not cover [3]. Examples are kidney cysts, deafness inherited through the mother, or loss of fat tissue in certain areas of the body [3].

The data needed depend on the time since diagnosis [1] [2]. After the first six months, you need your current age, age at diagnosis, height, weight, latest HbA1c, treatment and whether your parents have diabetes [1]. For a child in the first six months after diagnosis, you need the HbA1c at diagnosis, whether the parents have diabetes, polyuria and, if available, the autoantibody results [2].

The calculator is suitable for diabetes that started between ages 1 and 35 [1]. Diabetes that starts in the first six months of life is investigated directly with genetic testing, and between 6 and 12 months genetic testing may be considered [5]. For diabetes that started at age 18 or later, the calculator is used only after the first six months from diagnosis [2]. The Exeter model was built on people of European (Caucasian) origin, and the model for children on children from northern Europe [1] [2]. In people of other origins, the real probability of MODY may be different, most often lower [1] [6].