Nondiabetic relatives of probands with IDDM who are in the first two decades of life, are members of multiplex pedigrees, and have increased titers of islet-cell antibodies are the most likely to contract IDDM themselves.

Several studies suggest a higher incidence of insulin-dependent diabetes mellitus (IDDM) among the offspring of men with the disease than among those of female diabetics. Differential transmission by the father of genes that predispose to diabetes may explain this phenomenon. To test this hypothesis, we examined parent-to-offspring transmission of HLA haplotypes and DR (D-related) alleles in 107 nuclear families in which a child had IDDM. We observed that fathers with a DR4 allele were significantly more likely to transmit this allele to their diabetic or nondiabetic children than were mothers with a DR4 allele (72.1 vs. 55.6 percent, P less than 0.001). No differences between parents were observed for HLA-DR3; however, DR3 was transmitted significantly more than 50 percent of the time from either parent (P less than 0.001). These data suggest that differential parental transmission of the HLA-DR4-linked diabetes-predisposing allele may explain the higher risk of diabetes among children of diabetic fathers than among those of diabetic mothers. In addition, the excess transmission of diabetogenic HLA alleles from parent to offspring may explain how these deleterious genes continue to recur at such high frequencies in the general population.

The goal of this study was to describe a patient who developed insulin-dependent diabetes mellitus (IDDM) after donating a kidney to his sibling and to suggest a possible solution to prevent such an occurrence. A 42-yr-old man was found to have islet cell autoantibodies (ICAs) as part of a screening program of first-degree relatives with IDDM. Two years previously, he had donated his kidney to his HLA-identical sibling with long-standing IDDM. Both oral and intravenous glucose tolerance tests demonstrated a gradual loss of insulin secretion and increasing glucose intolerance until the patient developed IDDM 6 yr after the nephrectomy. Whether the presence of ICA is an absolute contraindication to being a kidney donor could be debated. Nonetheless, ICA should be used as a screening test to identify individuals at risk for subsequent IDDM. For those found to be positive, counseling should be provided.