Predictors of IDDM recurrence risk in offspring of Danish IDDM patients

Abstract

It has previously been observed that offspring of mothers with insulin-dependent diabetes mellitus (IDDM) have a lower risk of IDDM than offspring of IDDM affected fathers. To assess the offspring IDDM recurrence 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 population). 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 transmission rate was confirmed. The cumulative IDDM risk up to age 30 years was 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 offspring of probands diagnosed with IDDM after offspring birth, this observation needs to be confirmed in a larger population. In a subpopulation of the 2380 offspring, whose parents were all diagnosed with IDDM before offspring birth, the recurrence risk was significantly increased 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 was found in maternal offspring. Using the Cox proportional hazards model on this offspring subpopulation we found that paternal age at IDDM onset was the only statistically significant predictor of IDDM recurrence risk. Our findings may be important for counselling families in which one parent has IDDM.

Characterization of new polymorphisms in the 5′UTR of the human interleukin-1 receptor type 1 (IL1R1) gene: linkage to type 1 diabetes and correlation to IL-1RI plasma level

“…25,26 All families were unrelated, and all probands fulfilled the WHO diagnostic criteria for T1DM and were diagnosed before age 30 years. The 103 simplex families included 103 affected offspring and 112 non-affected offspring.…”

No evidence for linkage in the promoter region of the inducible nitric oxide synthase gene (NOS2) in a Danish type 1 diabetes population

“…All diabetic patients were diagnosed according to WHO criteria for type 1 diabetes and were diagnosed before the age of 30 years (median 10.7 years; range 0-30 years). 29,30 The Danish National Ethics Committee approved the study.…”

“…For participating departments in the DSGD: see Pociot et al 29 Contributing members of DIEGG: see Lorenzen et al 30 Anna-Margrethe Flarup are thanked for expert technical assistance.…”

Mutation analysis of suppressor of cytokine signalling 3, a candidate gene in Type 1 diabetes and insulin sensitivity

“…We also examined the identified variants for an association with Type 1 diabetes mellitus and insulin sensitivity. [19,20]. HLA stratification was performed for all probands and/or affected offspring, who were subsequently divided into high-risk DR3/4 heterozygous and non-high-risk (non-DR3/4 heterozygous) HLA-types.…”