Maturity-onset diabetes of the young: clinical heterogeneity explained by genetic heterogeneity.

摘要: Maturity-onset diabetes of the young (MODY) can be defined by clinical characteristics early-onset Type 2 (non-insulin-dependent) and autosomal dominant inheritance. Mutations in four genes have been shown to cause MODY: glucokinase, hepatic nuclear factor 1 alpha (HNF1alpha), 4 (HNF4alpha) insulin promoter [corrected] (IPF1). In white Caucasians it is now possible define gene most patients with a diagnosis MODY. Each involved MODY has its own specific physiological characteristics. Patients mutations glucokinase mild fasting hyperglycaemia throughout life, rarely require medication or develop microvascular complications. The principle pathophysiology stable beta-cell dysfunction characterized reduced sensing glucose pancreas. HNF1alpha normal tolerance early childhood usually present symptomatic their late teens adulthood. They show increasing treatment requirements frequent underlying defect progressive failure, lesion failure increase secretion levels. HNF4alpha IPF1 similar picture although may diagnosed later. There are other whom genetic still unknown. Molecular testing offers possibility making firm allows prediction future course. role predictive non-diabetic subjects within families uncertain at present. Preliminary evidence suggests that maintaining sensitivity avoiding obesity regular physical exercise help delay onset diabetes.