Early-Pregnancy Cytokines in Mothers to Children Developing Multiple, Persistent Islet Autoantibodies, Type 1 Diabetes, or Both Before 7 Years of Age

Problem Increased levels of serum cytokines in early pregnancy may increase the risk of type 1 diabetes in the offspring. Method of study Early-pregnancy (between 10 and 16 gestational weeks) serum samples from non-diabetic index mothers (n = 48) of children who developed islet autoimmunity, type 1 diabetes, or both before 7 years of age were analyzed for IFN-gamma, IL-10, IL-12, IL-13, IL-1 beta, IL-2, IL-4, IL-5, CXCL8, and TNF. Control mothers (n = 93) were matched for age, sampling date, and HLA-DQ genotypes. Results IFN-gamma (P = 0.02) and IL-1 beta (P = 0.04) were elevated in the index mothers. All cytokines except IL-4 were highly correlated (P < 0.0001). IFN-gamma [OR 1.39 (1.04, 1.85), P = 0.026] and possibly IL-2 [OR 1.21 (0.99, 1.48), P = 0.057] in early pregnancy were associated with an increased risk of multiple, persistent islet autoantibodies, type 1 diabetes, or both before 7 years of age in the offspring. However, the statistical significance for IL-2 was lost in the logistic regression when adjusted for gestational length at delivery and parity. Conclusion Increased Th1 cytokine levels during early pregnancy might contribute to an increased risk of islet autoimmunity, type 1 diabetes, or both in the offspring.