In Utero Dietary Exposures and Risk of Islet Autoimmunity in Children

Abstract

OBJECTIVE -The goal of this study was to examine whether maternal dietary intake of vitamin D, -3 fatty acids, and -6 fatty acids during pregnancy is associated with the appearance of islet autoimmunity (IA) in offspring. RESEARCH DESIGN AND METHODS -The Diabetes Autoimmunity Study in theYoung (DAISY) is recruiting at birth and following children at increased risk for type 1 diabetes, as determined by HLA-DR genotype or by family history of type 1 diabetes. A total of 233 mothers of newly recruited DAISY subjects were asked to recall their intake of food and nutritional supplements during the third trimester of pregnancy using the Willett food frequency questionnaire. Children were followed for an average of 4 years (range 0.8 -7.3 years) for the appearance of insulin, GAD 65 , and IA-2 autoantibodies. Sixteen children developed at least one autoantibody during this period. Unadjusted and adjusted hazard ratios (HRs) for the development of IA were estimated with survival analysis using a Weibull distribution.RESULTS -Maternal intake of vitamin D via food was significantly associated with a decreased risk of IA appearance in offspring, independent of HLA genotype, family history of type 1 diabetes, presence of gestational diabetes mellitus, and ethnicity (adjusted HR ϭ 0.37; 95% CI 0.17-0.78). Vitamin D intake via supplements, -3 fatty acids, and -6 fatty acids intake during pregnancy were not associated with appearance of IA in offspring.CONCLUSIONS -Our findings suggest that maternal intake of vitamin D through food during pregnancy may have a protective effect on the appearance of IA in offspring. Diabetes Care 26:3237-3242, 2003T ype 1 diabetes is a T-cell-mediated autoimmune disease characterized by the destruction of insulinproducing ␤-cells of the pancreas. The causes of type 1 diabetes are unknown, yet low concordance rates among monozygotic twins (1), a 10% progression rate among those genetically susceptible (2), migratory studies (3), and increasing worldwide incidence rates (4) suggest that genetic factors interact with environmental factors in the development of type 1 diabetes. These environmental factors have not been clearly identified.Type 1 diabetes is preceded by a preclinical stage termed islet autoimmunity (IA) that signals the beginning of ␤-cell destruction with the presence of autoantibodies against islet autoantigens. IA appears typically by 2 years of age and sometimes as early as 3 months of age in individuals with type 1 diabetic firstdegree relatives (5-7). Autoantibodies can be persistent for months or years, often predicting clinical diagnosis, or can be transient. Transient autoantibody positivity has not been associated with genetic risk factors (7,8), suggesting that environmental factors may be involved in suppressing persistent ␤-cell destruction.Increased expression of proinflammatory cytokines may be associated with the appearance and persistence of IA (9). Vitamin D and the -3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to modify th...

Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring

“…Unlike in a smaller US cohort study [15], we did not observe any inverse association between maternal intake of vitamin D from food and beta cell autoimmunity in the children. In the US study [15], the study population comprised 233 pregnant women and 16 children who were positive for one or more of IAA, GADA and IA-2A on at least one occasion (early pre-type 1 diabetes).…”

“…In the US study [15], the study population comprised 233 pregnant women and 16 children who were positive for one or more of IAA, GADA and IA-2A on at least one occasion (early pre-type 1 diabetes). Our survey, in comparison, involved 3,723 pregnant women and 138 children with repeated positivity for ICA and at least one other autoantibody (advanced pre-type 1 diabetes).…”

“…Thus our population should be large enough to show a potential protective effect of maternal vitamin D intake from food. In both the US [15] and our study, the intake of vitamin D from food was evaluated with a FFQ focusing on the third trimester and completed 1 to 3 months after delivery. Also the average follow-up time was similar at around 4 years, as was the average intake of vitamin D from food.…”

“…In a Swedish study, the use of vitamin D-containing supplements during pregnancy was associated with decreased autoimmunity against one autoantibody when children were 1 year old but not at later ages [14]. In a US cohort, maternal intake of vitamin D from food but not from supplements during pregnancy was associated with a decreased risk of islet autoimmunity appearance in the offspring [15]. In a Norwegian pilot case-control study, maternal cod liver oil supplementation (rich in vitamin D) during pregnancy was associated with a reduced risk of type 1 diabetes in the offspring [16].…”

“…Maternal intake of vitamin D from food or use of vitamin D-containing supplements during pregnancy were weakly associated with decreased risk of early beta cell autoimmunity in two cohort studies [14,15] and with clinical type 1 diabetes in one case-control study [16]. However, the results of these studies remain inconsistent.…”