Genetic tests may cut insulin need

Primary care genetics society Genetics and diabetes type, response to statins and bowel disease.

Treatment of maturity onset diabetes of the young (MODY) can be significantly improved by knowing its genetic basis and some patients can even be taken off insulin.

Mark Walker, professor of molecular diabetic medicine at Newcastle University, urged GPs at the Primary Care Genetics Society conference in Newcastle last week to refer their MODY patients for genetic testing.

Distinguishing between MODY2 and MODY3, the most common types, can allow some patients to stay off therapy while protecting others by using early sulphonylurea treatment.

The gene mutations causing common forms of MODY are highly penetrant, Professor Walker said.

'The genetic heterogeneity contributes to the clinical heterogeneity and identifying the responsible gene can influence clinical management,' he said.

Patients with MODY3, the commonest form of MODY, caused by a mutation in the hepatocyte nuclear factor-1-alpha gene on chromosome 12, see rapid progression of their diabetes to insulin-dependency and have a high rate of small vessel complications. But they are hypersensitive to sulphonylureas and can react to a standard starting dose of 80mg gliclazide with hypoglycaemia.

'If a young person who is newly diagnosed, with a strong family history, does not give a full dose of sulphonylureas, assume it could be MODY,' Professor Walker said.

Fasting glucose levels are high and young people are started on insulin but can be treated with sulphonylureas, he said.

Mutations in the glucokinase gene on chromosome seven cause MODY2 in 95 per cent of patients by the age of 40 but rapid progression of the diabetes and small vessel complications are rare.

'This is a stable condition with a low risk of complications,' he said. MODY accounts for 1-3 per cent of type-2 diabetes and GPs typically have one or two patients.

Professor Walker urged referral of diabetics under 40 without ketones at diagnosis who show a strong family history and sensorineural deafness, as they might have mitochondrial diabetes.

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