On the Heredity of Diabetes Mellitus and its Interrelationship with some other Diseases

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Abstract
The purpose of this investigation was to calculate the mode of inheritance and the gene-frequency of diabetes mellitus as well as the interrelationship between diabetes and some other diseases. Some generally applicable formulae for such calculations are given. Male diabetics between the ages of 17 and 25 years in a well defined geographical area, all 18-year-old male relatives of diabetics in that area, and age-matched controls were investigated. Diabetes occurred with increased frequency among relatives of juvenile diabetics and the distribution of the disease was compatible with the assumption of a uniform diabetic gene. An autosomal recessive mode of inheritance seemed to be the most likely transmission of diabetes mellitus. Then the mutant allele would occur at about 30% of the general population of the investigated area. Penetrance would occur during lifetime in about 70% of male and 90% of female homozygotes. If penetrance occurs among heterozygotes it appears to be low. Dominant inheritance seemed to be less likely but could not be excluded. The proportion of pathogenic alleles can then be calculated to be of the order of 0.05 with penetrance among about 25% in male and 30% in female gene carriers. The possibility of different genotypes manifesting the same or similar clinical picture could not be excluded but appeared less likely. If a main genotype is assumed the occurence of aberrant genotypes with similar manifestations of the disease must be low. The frequency of cerebral hemorrhage, myocardial infarction and gallstone is increased among diabetics, and in the diabetes gene carrier. The frequency of cancer is decreased among diabetics, and in the diabetes gene carrier.

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