Robert Moulder, M. Karoliina Hirvonen, Tommi Välikangas, Tomi Suomi, Lut Overbergh, Mark Peakman, Søren Brunak, Chantal Mathieu, Mikael Knip, Laura L. Elo, Riitta Lahesmaa
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引用次数: 0
Abstract
Aims/hypothesis
While investigating markers for declining beta cell function in type 1 diabetes, we previously demonstrated 11 statistically significant protein associations with fasting C-peptide/glucose ratios in longitudinal serum samples from newly diagnosed (ND) individuals (n=86; 228 samples in total) participating in the INNODIA (Innovative approaches to understanding and arresting type 1 diabetes) study. Furthermore, comparison with protein measurements from age- and sex-matched autoantibody-negative unaffected family members (UFMs, n=194) revealed differences in the serum levels of 13 target proteins. To further evaluate these findings, we analysed longitudinal serum drawn during the first year after diagnosis from a new group of ND individuals subsequently enrolled in the study, together with samples from additional UFMs.
Methods
To validate the previously reported statistically significant protein associations with type 1 diabetes progression, selected reaction monitoring (SRM) MS analyses were carried out. Sera from individuals diagnosed with type 1 diabetes under the age of 18 years (n=146) were collected within 6 weeks of diagnosis and at 3, 6 and 12 months after diagnosis (560 samples in total). The resulting SRM data were compared with fasting C-peptide/glucose measurements, which were used as a proxy for beta cell function. The protein data were further compared with cross-sectional SRM measurements from age- and sex-matched UFMs (n=272).
Results
Our results confirmed the presence of significant (p<0.05) inverse associations between fasting C-peptide/glucose ratios and peptides from apolipoprotein B-100, apolipoprotein M and glutathione peroxidase 3 (GPX3) in ND individuals. Additionally, we observed consistent differences in the levels of ten of the 13 targeted proteins between individuals with type 1 diabetes and UFMs. These proteins included GPX3, transthyretin, prothrombin, apolipoprotein C1 and afamin.
Conclusions/interpretation
The validated results reflect the landscape of biological changes accompanying type 1 diabetes. For example, the association of the targeted apolipoproteins with fasting C-peptide/glucose ratios in the first year after diagnosis is likely to relate to lipid abnormalities observed in individuals with type 1 diabetes, and reiterates the connection of apolipoproteins with the underlying changes accompanying the disease. Further research is needed to explore the clinical value and relevance of these targets.
期刊介绍：
Diabetologia, the authoritative journal dedicated to diabetes research, holds high visibility through society membership, libraries, and social media. As the official journal of the European Association for the Study of Diabetes, it is ranked in the top quartile of the 2019 JCR Impact Factors in the Endocrinology & Metabolism category. The journal boasts dedicated and expert editorial teams committed to supporting authors throughout the peer review process.
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