Predictors of long-term glycemic control, pancreatic function and BMI trajectory in children with type 1 diabetes

Abstract: Background: The maintenance of normal metabolic control underpins all management of insulin dependent diabetes whether in terms of preserved beta-cell function, body composition, or family support. The hypothesis of this work was that preserved C-peptide predicts better glycemic control and lowers risk of severe hypoglycemia. It was additionally investigated whether Body Mass Index (BMI) and family structure contributes to the prediction of long-term glycemic control. Objectives: This thesis aimed to 1) identify the factors associated with residual C peptide production at least 10 years after diagnosis, 2) evaluate the association of BMI trajectory and long-term glycemic control, 3) identify early characteristics associated with rapid or slow decline of beta-cell function and how it affects the clinical course, and 4) investigate the relations of family structure at diagnosis and long-term glycemic control. Methods: Data from four cohorts were used: In the Uppsala cohort, measurement of long-term residual C-peptide was undertaken using ultrasensitive C-peptide ELISA in 73 children and adolescents <25 years, BMI trajectory prior diagnosis was evaluated in 295 children, while family structure at diagnosis was evaluated in 215 children in relation to glycemic control. In the Linköping cohort, stimulated C-peptide was assessed by mixed meal tolerance test in 50 children. Results: The cohort studies showed that better early glycemic control predicted long term residual C-peptide and that long term residual C-peptide, in turn, was protective against severe hypoglycemia. Additionally, BMI trajectory was predicted by BMI prior to the presentation of type 1 diabetes. There was no association with glycemic outcome. Children living in a whole family had a lower probability of long-term dysglycemia. Conclusions: Residual C-peptide is important for better glycemic control and to reduce complications in children with type 1 diabetes. Family structure, but not BMI trajectory, contributes to the prediction of long-term glycemic control. However, more research is needed to understand how to preserve the beta-cell function in children and to target and support families in those children with early deteriorating glycemic control to reduce future complications.