Abstract

The presence of low-grade inflammation has been reported in people with type 2 diabetes and related to the development of (macro)vascular complications. Whether systemic inflammation is present in type 1 diabetes and linked to long-term complications remains unknown. We used a targeted proteomics approach to compare inflammation in people with type 1 diabetes and type 2 diabetes with control subjects and linked these proteins to diabetes related characteristics and complications. We included 233 participants with type 1 diabetes, 387 participants with type 2 diabetes and 150 healthy controls. Plasma was collected and used to determine high sensitive C-reactive proteins (hs-CRP) and an additional 92 inflammatory proteins using the Olink proteomics platform. Compared to healthy controls, 41 circulating inflammatory proteins were higher in type 1 diabetes (FDR < 0.05) and 64 inflammatory proteins in type 2 diabetes (FDR < 0.05) (including CXCL5, IL-15RA, MCP-4 and AXIN1 for both groups). HbA1c levels were positively associated with 21 inflammatory proteins (including CDCP1, FGF-21, HGF and IL-18R1) in type 1 diabetes (FDR < 0.05), whereas a positive association existed between body mass index (BMI) and 26 inflammatory proteins (including IL6, IL17C, FGF-23 and CSF-1) in type 2 diabetes. Inflammatory proteins associated with the presences, of complications, particularly nephropathy, were similar in both type 1 and type 2 diabetes. FlT3L and EN-RAGE were associated with the development of cardiovascular disease (CVD) in type 2 diabetes. Both type 1 diabetes and type 2 diabetes are associated with increased circulating inflammatory protein concentrations, but the increase is more pronounced in type 2 diabetes. These results suggest both differences in drivers of inflammation between type 1 diabetes and type 2 diabetes as well as potential similarities in pathways involved in the development of diabetes-associated complications.

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