Question

How important are genetics in diabetes?

Answer

There are at least three different disease processes contributing to the primary diabetic state, and in addition there are secondary causes of diabetes, such as pancreatitis, haemochromatosis, Cushing's syndrome, acromegaly and phaeochromocytoma.

Type III diabetes is found particularly in India and East Africa, and seems to be due to multiple small calculi in the fine branches of the pancreatic duct. There is no genetic link.

Type I diabetes is a result of autoimmune destruction of the Islets of Langerhans. Susceptibility to type I diabetes has a substantial genetic component. The disease runs in families, with a 6% risk that a sibling will develop the disease, compared with a 0.4% risk in the normal population. However the pattern of inheritance is complex. Twin studies suggest that approximately 1/3 of the disease susceptibility is genetic. Several loci are probably involved, and it may be that the heterozygote has an increased susceptibility compared to the homozygote on some of the loci. There is no evidence that the disease transmission is sex-linked.

Type II diabetes lacks association with circulating autoimmune antibodies, and is associated more often with later life and high levels of insulin in the serum.In type II diabetes mellitus, it is possible that genetic mutations may account for the disease phenotype in a small number of patients. However, the disease displays substantial genetic heterogeneity. There are for instance some ethnic populations with an extremely high prevalence of the disease. Furthermore there are several specific syndromes where extreme insulin resistance is evident, such as leprechaunism and Rabson-Mendenhall syndrome. Severe forms of insulin resistance are associated with homozygocity for insulin receptor mutations, but heterozygous patients occasionally have more modest degrees of insulin resistance consistent with a diagnosis of type II diabetes. Studies suggest that insulin receptor mutations are however more important in the rare syndromes of severe insulin resistance than in the more common forms of type II diabetes. There are patterns of type II diabetes that are consistent with a dominant mode of inheritance and 50% of the children are affected by glucose intolerance at an early age. There is no evidence of any sex link. We should emphasise that we are talking about rare types of type II disease and the genetics of the more common larger proportion of type II patients is not really well worked out.