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Some aspects of the genetics and etiology of spontaneous diabetes mellitus

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Summary

Human DM consists of a heterogeneous group of metabolic disorders which have as a common denominator diminished carbohydrate tolerance. Genetic factors are probably important in the etiology of almost all cases of DM, excluding perhaps only those produced by pancreatectomy. However, the precise mechanisms of expression of the genetic defects related to DM have been elucidated only in a few cases whereas the majority, especially those of MOD, should probably be considered multifactorial in origin (complex interplay between polygenic and environmental factors). Several less frequent forms of DM can be inherited in a typical Mendelian way, either alone (e.g. probably MODY) or associated with certain well defined genetic diseases (where carbohydrate intolerance is a frequent component of the clinical picture). JOD should most probably be attributed to the action of some as yet unidentified environmental factors, perhaps viruses, in subjects with a particular genetic predisposition. This predisposition seems to be closely associated with certain HLA antigens, particularly those of the D series. The mechanisms responsible for this association remain a matter of controversy. Autoimmune phenomena appear to be important in the pathogenesis of JOD. The ability of certain viruses to induce DM has been clearly demonstrated in a few experimental systems by infecting genetically susceptible animals. Under such conditions, DM is produced by a destruction of the pancreatic islets. On the other hand, there is as yet no conclusive evidence concerning the possibility that exogenous and/or endogenous viruses may play a role in the etiology of human DM. Patients with certain chromosome abnormalities are prone to develop DM. On the other hand, there are no available data concerning a possible effect of DM on the incidence of chromosome abnormalities in patients with the disease or in the embryos and fetuses of diabetic mothers. The possibility of congenital transmission of a predisposition to DM (which might possibly be inherited thereafter) through the action of some unknown epigenetic mechanisms has been suggested on the basis of limited clinical and experimental observations. However, further information is necessary in order to clarify the validity of such a curious possibility.

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  1. Instituto de Medicina Experimental, Universidad Central de Venezuela, Apartado Postal 50587, Caracas 105, Venezuela

    Enrique Pimentel

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Pimentel, E. Some aspects of the genetics and etiology of spontaneous diabetes mellitus. Acta diabet. lat 16, 193–201 (1979). https://doi.org/10.1007/BF02629112

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