Diabetes treatment response determined by genetic variation

Genetic variation plays a large part in explaining why metformin is much better at lowering blood glucose in some people with diabetes than others, a UK study suggests.

Blood samples: variation in HbA1c reduction down to genetics (photo: JH Lancy)

Kaixin Zhou and colleagues from the University of Dundee used data from 3,736 individuals to look for gene variants linked to glycaemic response to metformin.

The researchers looked at the reduction in HbA1c achieved with 18 months of beginning metformin treatment.

They found that 36% of the difference across individuals in glycaemic response to metformin could be explained by inherited genetic variation. This suggests that response to metformin is more strongly linked to genetic factors than individuals' height or the age at which they develop diabetes.

Mr Zhou presented the findings at the 2012 meeting of the European Association for the Study of Diabetes in Berlin, Germany on 2 October 2012.

'We now know that a rather large chunk of the variance in metformin response is contributed by genetic factors,' he said.  'What are the genes actually doing towards this contribution? Well,  we don't know too much about that.'

Mr Zhou said few previous studies had looked at the extent to which genetic variations affect responses to drug treatment. This is principally because genetic research often relies on studies of twins or other relatives, and individuals rarely suffer the same diseases and receive the same treatment.

The study found one specific gene linked to variation in glycaemic response to metformin. But this gene only explained 2.5% of the variation seen across individuals.

'Compared to the 36% heritability that we estimated, this is way down, he said.

'There are at least 11 other metformin response genes out there. We need large genome-wide association studies to identify other metformin genes.'

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