Early glucose metabolism in children at risk for type 1 diabetes based on islet autoantibodies compared to low-risk control groups

Abstract

Background: Anatomic variation or early differences in glucose metabolism have been linked to the development of type 1 diabetes. We aimed to describe early glucose metabolism based on HbA1c, oral glucose tolerance test (OGTT), and random plasma glucose years before the presentation of type 1 diabetes in five risk groups based on autoantibody combinations. For the first time, we were able to include for comparison children with very low risk of progression to type 1 diabetes.

Methods: The Finnish Diabetes Prediction and Prevention birth cohort study screened newborn infants for HLA susceptibility to type 1 diabetes since 1994. Those carrying a risk genotype were prospectively followed up with islet autoantibody testing. Glucose parameters were obtained starting from the time of seroconversion. By 31 August 2014, 1162 children had developed at least one islet autoantibody and were included in the current study. Type 1 diabetes was diagnosed in 335 children (progressors). In the non-progressor groups, 207 developed multiple (≥2) biochemical islet autoantibodies, 229 a single biochemical autoantibody, 370 ICA only, and 64 transient autoantibodies. Children were divided into five risk groups. Glucose metabolism was evaluated.

Results: We observed lower HbA1c values in early follow-up 4.5 to 6.0 years before diagnosis in the progressors when compared to the same time in children with a single biochemical autoantibody or low-risk (ICA only and transient) participants, who did not progress to clinical type 1 diabetes. However, no such differences were observed in OGTTs or random plasma glucose. The variation was minimal in glucose values in the low-risk groups.

Conclusion: We report the possibility of early alteration in glucose metabolism in future progressors. This could suggest early defects in multiple glucose-regulating hormones.

Keywords: HbA1c; Islet autoantibodies; Type 1 diabetes; glucose metabolism; oral glucose tolerance test (OGTT); preclinical; random plasma glucose.

Figure 1

Flow-chart for the identification of the current study groups. The follow-up ended on August 31, 2014.

Figure 2

Adjusted mean HbA1c, during the follow-up in children divided into five risk groups. The last points are diagnosis of type 1 diabetes (progressors, black squares) or the last follow-up visit by 31 August 2014. Whiskers show 95% confidence intervals of the adjusted mean in the linear mixed model. In the early values during 4.5–6 years before diagnosis, the progressors showed significantly lower HbA1c values compared to single biochemical autoantibody and low-risk groups. Toward diagnosis, HbA1c values started to increase in the progressors.

Figure 3

Adjusted mean plasma glucose levels in OGTT [(A) =fasting and (B) =2-h plasma glucose], during the follow-up in children in three risk groups (OGTTs were not performed in the ICA only and transient autoantibody positivity groups). The last points are diagnosis of type 1 diabetes (progressors, black squares) or the last follow-up visit by August 31, 2014. Whiskers show 95% confidence intervals of the adjusted mean in the linear mixed model. No significant differences in the early plasma glucose values were observed between the groups. OGTT values started to rise toward diagnosis in the progressors.

Figure 4

Adjusted mean random plasma glucose during the follow-up in children in five risk groups. The last points are diagnosis of type 1 diabetes (progressors, black squares) or the last follow-up visit by August 31, 2014. Whiskers show 95% confidence intervals of the adjusted mean in the linear mixed model. No significant differences in the early random plasma glucose values were observed between the groups. Random plasma glucose values started to increase toward diagnosis in the progressors. .