[Genetics of diabetes mellitus (author's transl)]

Since Pincus and White's claim in 1933 that diabetes mellitus is an inherited disease, the precise mode of inheritance remains a matter of dispute. The reason for the controversy is that the geneticist is confronted with a number of impediments to genetic analysis. As pointed by Neel, "diabetes mellitus is in many respects a geneticists nightmare". The obstacles are : 1) a precise definition of diabetes is difficult to establish, 2) the frequency of the disease which is sex and age dependent is not well known, 3) the probability of genetic heterogeneity is great but whether early onset and late onset diabetes are different genetic diseases or the same one remains controversial, 4) the basic defect (s) is unknown, 5) environmental factors (e.g. nutritional status) influence the frequency of the disease. Despite these problems many studies have been devoted to the mode of inheritance of diabetes mellitus. Many authors favour an autosomal recessive mechanism. However, low penetrance (25 %) is necessary to support this mode of inheritance. Simple autosomal dominant mode of inheritance has also been suggested, but this pattern fits only few families. The majority of geneticists think, at the present time, that diabetes has a multifactorial mode of inhritance. The heritability which express the extent to which the phenotypes exhibited by parents are transmitted to their offspring is in the neighbourhood of 50%. Many arguments favour this mode of inheritance: 1) low penetrance is necessary to aistinct genetic diseases, and especially in chronic glaucoma, which also have a multifactorial mode of inheritance; in particular, one must note the association between glucose intolerance and ocular hypertension induced by dexamethasone, 3) the association between diabetes and antigen A of the ABO system and antigens HL-A8 and W 15 of the HL-A system.