However, recent analyses have also demonstrated ABCC8 gene mutations in patients with monogenic diabetes (maturity onset diabetes of the young, MODY), with milder clinical phenotypes and later onset of hyperglycemia.
A mutation in ABCC8/SUR1, leading to a Y356C substitution in the seventh membrane-spanning alpha-helix, was observed in a patient diagnosed with hyperglycemia at age 39 years and in two adult offspring with impaired insulin secretion.
Our results suggest that SUR1 exon 16-3c/t polymorphism is only a partial determinant of acute hyperglycaemia-cardiovascular risk factor in type 2 diabetes.
Although ketoacidosis is frequent at presentation, SUR1 mutations associate mainly with transient hyperglycemia, with possible recurrence later in life.
The diabetes associated exon 16 -3t variant of the SUR1 gene associates with a functional change of the beta cell as reflected by reduced second-phase insulin secretion in response to a standardized hyperglycaemia in normal and impaired glucose tolerant subjects.
Since we have previously reported linkage between SUR1 and hyperglycemia, the present association between a SUR1 variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group raises the possibility of primary insulin hypersecretion as an antecedent of type 2 diabetes in at least some individuals from this population.