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Maturity-onset diabetes of the young (MODY) is a genetically and clinically
heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM)
characterised by early onset, autosomal dominant inheritance and a primary
defect in insulin secretion. To date, three MODY genes have been identified on
chromosomes 20q [hepatocyte nuclear factor (HNF-4 alpha)/MODY1], 7p
(glucokinase/MODY2) and 12q (HNF-1 alpha/MODY3). Mutations in glucokinase/MODY2
result in mild chronic hyperglycaemia due to reduced pancreatic beta-cell
responsiveness to glucose as well as decreased net accumulation of hepatic
glycogen and increased hepatic gluconeogenesis following meals. In contrast,
MODY1 and MODY3 are characterised by severe insulin secretory defects and major
hyperglycaemia associated with microvascular complications. The role of the
three known MODY genes in susceptibility to the more common late-onset from of
NIDDM remains uncertain. Genetic studies seem to exclude any function as major
susceptibility genes, although they may play a minor role in a polygenic context
or a major role in particular populations.
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