PREDICTORS OF IDDM RECURRENCE RISK IN OFFSPRING OF DANISH IDDM PATIENTS

It has previously been observed that offspring of mothers with insulin -dependent diabetes mellitus (IDDM) have a lower risk of IDDM than off spring of IDDM affected fathers. To assess the offspring IDDM recurren ce risk in a Danish population-based study and to investigate parental and offspring-related biological variables that might influence this risk, we identified 2726 IDDM probands and their 2826 offspring from a background population of 1.725 million people (33% of the Danish popu lation). Current age of probands was 20-65 years and their age at IDDM onset was 30 years or less. Sixty nine offspring (2.4%) were affected with IDDM. The sex difference in the parental-offspring IDDM transmis sion rate was confirmed. The cumulative IDDM risk up to age 30 years w as found to be significantly decreased in maternal offspring compared to paternal offspring (2.3 +/- 0.6 and 5.7 +/- 0.9%, RR = 2.40, 95% CI 1.30-4.47; p = 0.004) only if parents were diagnosed with IDDM before birth of the offspring. However, due to the low number of diabetic of fspring of probands diagnosed with IDDM after offspring birth, this ob servation needs to be confirmed in a larger population. In a subpopula tion of the 2380 offspring, whose parents were all diagnosed with IDDM before offspring birth, the recurrence risk was significantly increas ed in offspring of male probands diagnosed up to age 17 years compared to offspring of fathers diagnosed at older ages (8.5 +/- 1.8 and 3.6 +/- 1.0%; RR = 2.27, 95% CI 1.21-4.25; p = 0.006). No such relation wa s found in maternal offspring, Using the Cox proportional hazards mode l on this offspring subpopulation we found that paternal age at IDDM o nset was the only statistically significant predictor of IDDM recurren ce risk. Our findings may be important for counselling families in whi ch one parent has IDDM.