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Diabetes Metab Res Rev. 2017 Sep;33(6). doi: 10.1002/dmrr.2900. Epub 2017 May 16.

Characteristics of the pre-diabetic period in children with high risk of type 1 diabetes recruited from the general Swedish population-The ABIS study.

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Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Pediatric Clinic, County Council of Östergötland, Linköping, Sweden.
Division of Diabetes and Celiac disease, Department of Clinical Sciences, Lund University, Malmö, Sweden.



There is a need for increased understanding of the pre-diabetic period in individuals with high risk of type 1 diabetes from the general population.


High-risk children (n = 21) positive for multiple islet autoantibodies were identified by autoantibody screening within the All Babies in Southeast Sweden study. The children and their parents were enrolled in a 2-year prospective follow-up study aiming to characterize the pre-diabetic period. Blood samples were collected every 6 months for measurement of C-peptide, HbA1c, fasting glucose, and autoantibodies. Human leukocyte antigen-genotype was determined, and oral glucose tolerance test was performed every 12 months.


Despite positivity for multiple autoantibodies, 9 out of 21 individuals had low-risk human leukocyte antigen-genotypes. Children who progressed to manifest diabetes (progressors, n = 12) had higher levels of IA2A and ZnT8A than children who did not (non-progressors, n = 9). Impaired glucose tolerance and impaired fasting glucose was observed to the same extent in progressors and non-progressors, but HbA1c increased over time in progressors in spite of increased C-peptide.


Autoantibodies to IA2 and ZnT8 may be useful discriminators for disease progression in at-risk children from the general population. Dysglycemia was observed long before diagnosis, and difficulties in maintaining glucose homeostasis despite increased C-peptide indicate that insulin resistance might be an important accelerator of disease in risk individuals.


T1D high-risk; islet autoantibodies; pre-diabetes; type 1 diabetes

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