Vitamin C, Iron, Nitrate, and Nitrite in the Development of Islet Autoimmunity and Type 1 Diabetes: Two Prospective Birth Cohort Studies of Individuals at Increased Genetic Risk of Type 1 Diabetes

Type 1 diabetes is the result of an autoimmune reaction against insulin-producing beta cells in the pancreas, leading to the eventual termination of insulin production. Since the body can no longer control blood glucose levels, lifetime insulin therapy is required. The causes and mechanisms are still relatively unknown, but the emergence of specific autoantibodies in blood circulation signifies islet autoimmunity development. Genetics and environmental triggers, such as diet, might affect inflammation markers, which either induce or suppress autoimmune reactions and further lead to development type 1 diabetes.

The aim of this thesis was to explore whether plasma vitamin C status in childhood is associated with the risk of type 1 diabetes development and whether vitamin C metabolism-related genotypes modify the association. Furthermore, the aim was to explore whether maternal intake of vitamin C, iron, nitrate, and nitrite during pregnancy is associated with the risk of developing type 1 diabetes.

This thesis was a part of multinational The Environmental Determinants of Diabetes in the Young (TEDDY) Study (n = 8,677) and Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study (n = 7,782). The children studied carry a high or moderate genetic risk for type 1 diabetes. Children were monitored for the emergence of autoantibodies associated with type 1 diabetes and the development of clinical type 1 diabetes between 3- and 12-month intervals up to 15 years of age (DIPP) or up to the diagnosis of type 1 diabetes (TEDDY). Childhood plasma vitamin C status was measured up to 6 years of age, and the genotypes related to vitamin C metabolism were assessed in the TEDDY Study. Maternal diet was assessed using a semiquantitative validated food frequency questionnaire (FFQ) covering total diet during 8th month of pregnancy in the DIPP Study. The statistical methods used were the Cox proportional-hazards model and condition logistic regression.

Childhood plasma vitamin C status was associated with a decreased risk of islet autoimmunity. Vitamin C metabolism-related genotypes did not modify this association. Maternal intake of vitamin C, iron, nitrate, or nitrite during pregnancy was not associated with the risk of islet autoimmunity or type 1 diabetes in offspring.

The results suggest that a high plasma vitamin C status in the early childhood might protect against islet autoimmunity. Maternal intake of vitamin C, iron, nitrate, or nitrite during pregnancy was not associated with childhood type 1 diabetes development. This may result from tightly regulated nutrient transportation in the placenta.