Although this association has been observed across many diabetic cohorts [151], it remained unclear whether: (i) it was mediated by AMPK activation by metformin; and (ii) it was a cell-intrinsic effect in the tumour progenitor cells themselves (for example, it might have been due to the ability of metformin to lower plasma glucose and/or insulin levels due to effects in other tissues or organs, such as the liver). The gene discussed is PRKAA2; the disease is neoplasm.