Differences in Risk of Insulin-Dependent Diabetes in Offspring of Diabetic Mothers and Diabetic Fathers

One of the best means of determining the risk of insulin-dependent diabetes mellitus in relatives of index cases is to study the offspring of matings between patients with diabetes and persons without the disease. If the affected parents are selected before the birth of any child, the frequency of insulin-dependent diabetes mellitus in the offspring should not be biased by the method of ascertainment. The purpose of this article is to report a new analysis of the data from one such study, which shows differences in the risk for offspring according to the sex of the affected parent, and to consider the implications of this finding for the possible role of heritable factors in insulin-dependent diabetes mellitus.The study identified patients through the medical records of the Joslin Diabetes Center for the period of 1928 to 1939. Eligible patients were those with diagnoses of insulin-dependent diabetes mellitus before the age of 20. Eighty-eight affected men produced 244 offspring, and 99 affected women produced 175 offspring. By age 20, 6.1 ±; 1.8 per cent (mean ±; SE) of the fathers with diabetes had the disease. This risk is similar to that reported for the siblings of patients with diabetes. By contrast, the risk of development of the disease in the offspring of affected mothers was only one-fourth as large (1.3 ±; 0.9 per cent). This is still about five times the cumulative risk found in the general population by age 20. The 4.8 per cent difference in the cumulative risks between the offspring of diabetic women and those of diabetic men is significant (P < 0.05; 95 per cent confidence interval, 2.1–10.8 per cent). Daughters and sons of the fathers with insulin-dependent diabetes mellitus were affected equally (six and five, respectively) and were combined in the analysis.The finding of different risks of diabetes in offspring according to the sex of the affected parent was unexpected. The authors examined studies from other countries and found similar results, i.e., lower rates of diabetes in the offspring of diabetic mothers than in those of affected fathers. The results from several types of studies are summarized in Table 1.Another source of evidence regarding sex differences in the transmission of insulin-dependent diabetes mellitus from parent to child is found in studies of the prevalence