DIABETES SECONDARY TO GENETIC-DISORDERS

Diabetes may be associated with many genetic disorders. The scientific importance of these often rare disorders resides in the insight they may provide into the possible mechanisms of common diabetes. The type of diabetes varies in these syndromes. Non-insulin-dependent diabetes (NIDDM), clinically similar to common NIDDM, may be found in some syndromes (e.g. Werner's syndrome). In others there may be considerable insulin resistance, such as that present in ataxia telangiectasia. Extreme insulin resistance due to abnormal insulin receptor function is found in the Mendenhall syndrome. The mechanism of diabetes is more obscure in acute intermittent porphyria (AIP), although haem deficiency affecting the cytochrome chain raises interesting possibilities. In glycogen storage disease type I, the diabetes is associated with insulinopenia, following an earlier period in the disease when hypoglycaemia is the rule. IDDM, clinically similar to the common form, is present in the autoimmune polyglandular syndromes. Although a change in the lean: fat ratio is common in many neuromuscular disorders, mechanisms other than insulin resistance would seem to operate. The increased incidence of diabetes in heterozygotes for some of these genetic disorders raises the possibility that many common diabetics are, in fact, heterozygotes for some other disorder. The increased frequency of diabetes in Klinefelter's syndrome, Turner's syndrome and possibly Down's syndrome leads to the hypothesis that non-disjunction may, in some way be associated with the predisposition to diabetes. In several syndromes there is an increased incidence of diabetes in otherwise unaffected relatives of individuals with these syndromes. It is impossible to assess what proportion of common NIDDM or IDDM is made up of heterozygotes for these genetic syndromes. © 1992 Baillière Tindall.