Genetics of Diabetes in Childhood

The syndrome of diabetes, centered on chronic hyperglycaemia, is categorised into two major clinical stereotypes: type 1 (‘juvenile’, insulin-dependent) and type 2 (‘adult onset’, non-insulin-dependent). Type 1 diabetes (T1D) is an autoimmune disease in which hyperglycaemia is secondary to insulin deficiency, following destruction of pancreatic islet P cells by cell-mediated autoimmunity1,2. T1D is one of the most common chronic diseases beginning in childhood and accounts for greater than 90% of cases of childhood diabetes, with an overall prevalence rate of 0.2-0.5% across Caucasoid populations3. The incidence of type 1 diabetes is increasing world-wide4 and at least in several areas this increase is reported to be greater in the under 5-year olds5,6. In type 2 diabetes (T2D), hyperglycaemia can be attributed to defective glucose metabolism through pathways that are responsive to insulin (“insulin resistance”), a defect that appears to be present in many tissues including muscle, liver, fat and β cells. Although T2D is generally considered to be a polygenic ‘inborn error of metabolism’ disorder, its genetic and molecular basis in the vast majority of cases remains an enigma. In a minority of cases, presenting usually in childhood, monogenic defects are designated maturity onset diabetes of the young (MODY). A small but increasing proportion of childhood diabetes is T2D, related to the rising prevalence of childhood obesity in affluent young (MODY).