Definition, epidemiology, diagnosis and classification

Genetic defects of beta-cell function (formerly known as maturity-onset diabetes in the young, MODY subtypes)

Early-onset hyperglycemia before age 25 years
Monogenic, autosomal dominant mode of inheritance — at least two, preferably three, generations exhibiting a similar phenotype (although older relatives may not be diagnosed until older age)
Non-insulin-dependent for at least 5 years after diagnosis of diabetes
Impaired insulin secretion
Absence of severe ketosis

Some forms of these defects in beta-cell function may present with severe osmotic symptoms and may be misdiagnosed as type 1

But

Until recently specific genetic diagnosis was not possible in 15–20% of families with defects of beta-cell function, however
- A fourth variant is associated with defects in the insulin promoter factor (IPF1) — in the homozygous state associated with pancreatic agenesis
- A fifth variant is associated with mutations in HNF-1 — resulting in renal abnormalities particularly cystic kidney disease, which is normally congenital

Depends on underlying genetic disorder
Children and adolescents with glucokinase or transcription factor mutations only require healthy eating recommendations initially to achieve good glycemic control
Progressive beta-cell deficiency in some children with transcription factor mutations results in the need for oral hypoglycemic agents. HNF-1 variants may exhibit sensitivity to small doses of sulfonylureas (with the risk of hypoglycemia)
One-third of patients with mutations in HNF-1 may require insulin treatment, but this is usually in adulthood