Insulin Resistance Accelerates T1 Diabetes in Children

Insulin resistance could accelerate the risk of type 1 diabetes (T1D) in children with dysglycemia, according to a group of Swedish researchers.

Researchers led by Linda Akerman of the Division of Pediatrics in the Department of Clinical and Experimental Medicine at Linkoping University, Sweden, came to this conclusion after seeking to better understand the natural history of the pre-diabetic period.

The process in the autoimmune system that leads to T1D begins very early, and prior research has found that the presence of autoantibodies indicates an ongoing reaction that likely progresses to clinical disease. People who have those autoantibodies, who either do or do not also have the human leukocyte antigen (HLA) genotype, are at increased risk of T1D. However, even with those indicators being known, the researchers say, “the predictive value of additional measurements varies in different risk-cohorts, and there is still a gap in the understanding of the natural history of the pre-diabetic period”.

In order to learn more about the pre-diabetic period, researchers used the All Babies in Southeast Sweden (ABIS) birth cohort, which consists of 17,055 children. The members of the ABIS cohort are from the general population in Sweden, and allowed the researchers to identify and follow those who are at increased risk of developing T1D. Informing the children and their families of the higher risk allowed the researchers to also study the psychological aspects of risk awareness, while also working to characterize the pre-diabetic period and examine the factors involved in the disease either progressing or not progressing.

The ABIS cohort was enrolled between October 1, 1997 and October 1, 1999, and biological samples were taken at the time of birth as well as at the ages of 1 year, between 2.5 and 3 years, between 5 and 6 years, 8 years, and 11 to 12 years of age. Additionally, the families completed extensive questionnaires at regular intervals, describing environmental factors and family history of disease.

Autoantibody screening was done regularly, and the researchers report, “based on the detection of 2 or 3 different autoantibodies on at least 2 sampling occasions, a group of 46 children were considered at high risk for T1D”. Later sampling confirmed that 22 of the participants already had developed T1D by the age of 12. The 24 remaining children and their families were invited to participate in a follow up prospective study. A total of 21 subjects were included in the final analyses.

Each of the participants had blood drawn for HLA-genotyping, autoantibody, C-peptide, and HbA1c measurements. Additionally, oral glucose tolerance tests were performed. Follow ups were performed at 6, 12, 18, and 24 months either via home testing kits or at local primary care clinics.

At the end of the study, the researchers report, “Twelve participants out of the 21 included have developed diabetes to date, while the non-progressing individuals have been positive for multiple autoantibodies for a period of 8 to 16 years without developing symptomatic disease”. Nine of the participants had genotypes associated with a low risk of T1D, which leads the researchers to suggest that multiple autoantibodies should be used to detect risk.

The authors acknowledge that the number of participants in this study was small, but add they believe the data they generated makes a valuable contribution.

“Given the lack of T1D family history is as many as 85% of the people who develop the disease, addressing the natural history in cohorts other than those selected based on T1D kinship is of importance”.

The full study was published in the journal Diabetes/Metabolism Research and Reviews.

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