Sustained low-grade inflammation in young participants with childhood onset type 1 diabetes: The Norwegian atherosclerosis and childhood diabetes (ACD) study

Abstract

Background and aims: Persons with type 1 diabetes (T1D) have increased mortality from cardiovascular disease. Early inflammation is important in the development of atherosclerosis. We aimed to evaluate the extent of inflammation and difference in mean over a five-year period in young persons with T1D compared to healthy controls.

Methods: The Norwegian Atherosclerosis and Childhood Diabetes (ACD) study is a prospective population-based cohort study on atherosclerosis development in childhood-onset T1D compared to healthy controls, with follow-ups every fifth year. The original study cohort consisted of 314 children with T1D on intensive insulin treatment and 120 healthy controls of similar age. Circulating levels of VCAM-1, TNA-α, P-selectin, E-selectin, CRP, IL-6, IL-18, MCP-1, MMP-9 and TIMP-1 were measured by ELISAs at baseline and at the five-year follow-up.

Results: The group with T1D had mean age 13.7 (SD = 2.8) years, disease duration 5.6 (SD = 3.4) years and HbA1c 68 (SD = 13.1) mmol/mol at baseline. Levels of almost all inflammatory markers were significantly increased in the group with T1D compared to controls, and significant mean-difference between the two groups over the five-year period was observed in four markers: IL-18, P-selectin, E-selectin and TIMP-1.

Conclusions: The early low-grade inflammation present in young individuals with T1D five years after diagnosis is sustained at ten-year disease duration, with moderate changes for most markers of inflammation over time. The evolving inflammatory profile indicates an accelerated chain of events in the progression of early atheromatosis in T1D.

Keywords: Atherosclerosis; Cardiovascular risk factors; Childhood onset type 1 diabetes; Inflammation; Inflammatory markers.