Maturity onset diabetes of youth

MODY refers to a group of monogenic forms of diabetes with autosomal dominant inheritance. The causative mutations are all in genes that control production of insulin and thus MODY is characterised by relative insulinopaenia but ketosis is an unusual feature of MODY. Diagnosis can be confirmed by molecular genetic analysis. Treatment is by OHA or by insulin therapy depending on the type.

Has the patient been drinking more water and passing more urine than usual?

Polyuria and polydipsia are the cardinal symptoms of diabetes and occur when the blood glucose level exceeds the renal threshold for glucose excretion - usually approximately 10 mmol/L.

However, MODY often presents with relatively mild hyperglycaemia and therefore osmotic and other classical hyperglycaemic symptoms can be absent at presentation.

Has the patient noticed a change in eye sight, particularly an inability to focus?

Variable difficulty with focusing - that has been present for only a short period and is fluctuating - is due to osmotically driven swelling of the lens and varies as the degree of hyperglcaemia varies.

However, MODY often presents with relatively mild hyperglycaemia and therefore osmotic and other classical hyperglycaemic symptoms are often absent at presentation.

Has the patient lost weight without trying?

Significant weight loss in association with a new diagnosis of diabetes is a less common feature of MODY.

This feature, especially in a patient who is already lean, should prompt the physician to consider a diagnosis of type 1 diabetes or other causes of diabetes, for example post-pancreatitis diabetes.

Has the patient developed genital thrush?

Hyperglycaemia impairs neutrophil and macrophage function at the same time as producing a more favourable environment for micro-organisms to grow.

Infections generally are therefore more common in the hyperglycaemic patient and genital candidiasis is a particularly prevalent example.

However, MODY often presents with relatively mild hyperglycaemia and therefore osmotic and other classical hyperglycaemic symptoms are often absent at presentation.

Has the patient any other relatives with diabetes?

A thorough family history is essential to detect monogenic causes of diabetes such as MODY.

In addition, mitochondrial diabetes or APECED (auto-immune polyendocrinopathy, candidiasis and ectodermal dystrophy) might also be missed without a good family history being taken.

Because MODY is usually inherited as an autosomal dominant trait, the family history with members of each successive generation being affected ought to be fairly obvious.

To confidently diagnose MODY, there needs to be a strong family history of diabetes mellitus with onset before the age of 25. T2DM also however often runs quite strongly in families.

A complete absence of family history of diabetes doesn’t absolutely rule out the diagnosis of MODY but should at least prompt consideration of alternative diagnoses which may include T1DM or LADA. 

Is the patient taking any other medicines such as steroids?

This would increase the chances of steroid induced diabetes and reduce the probability of MODY.

Does the patient have a past medical history of pancreatitis, malabsorption, pancreatectomy or cystic fibrosis?

Any of these conditions may pre-dispose to loss of beta cell mass. If so, this would indicate a cause of diabetes other than MODY.

Is the patient completely asymptomatic?

As awareness of MODY increases there are an increasing number of first degree relatives of index cases being screened at a pre-symptomatic stage and found to have early, pre-symptomatic diabetes.

However, the history of family screening for a 'genetic' form of diabetes ought to be quite apparent. Because some forms of MODY present with relatively mild hyperglycaemia, diagnosis can also be made in an asymptomatic patient after the chance finding of an elevated blood glucose level.

What other clues may there be in the family history?

Are there family members with diabetes who have spent many years successfully managing with diet-only therapy and who have acquired very few, if any, diabetes complications? 

These features strongly suggest a diagnosis of a familial glucokinase mutation.

Are there family members with diabetes mellitus who have only required very low doses of sulphonylurea drugs, such as gliclazide or glibenclamide, for prolonged periods of time giving good control of their diabetes? 

Such a history is strongly suggestive of hepatocyte nuclear factor 1 alpha mutation.

Are there family members who have been diagnosed with T1DM but who have required very low doses of insulin to achieve good control of their diabetes, or who have later come off insulin therapy and required only tablet treatment, or who have had prolonged 'honeymoon' phases of their diabetes?

These features suggest the possibility of hepatic nuclear factor (HNF) 1α or HNF4α mutations.

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