Plasma proteomic profiles in prediabetes reversing to normoglycemia or progressing to diabetes in a year – a cross-sectional and prospective analysis

Aim To compare the fasting plasma proteome profiles of patients with normal glucose tolerance (NGT), prediabetes or type 2 diabetes (T2DM) at-onset, and one-year before, when all subjects had prediabetes.

Methods The concentrations of 1389 proteins were measured with Olink proteomics technology in fasting plasma from 100 subjects (25 T2DM, 50 prediabetes, 25 NGT) from Dresden who participated in the Prediabetes Lifestyle Intervention Study of German Diabetes Centers. For 80 subjects, the same proteins were also measured in plasma samples from one year before, when all subjects had prediabetes.

Results In our preliminary analysis, seven proteins differed significantly in their plasma levels between T2DM, prediabetes and NGT subjects (p<0.001 for one-way ANOVA). Among these 7 proteins, the concentrations of IL-1 receptor antagonist protein had the strongest correlations with fasting glucose (r=0.45), glucose AUC of the OGTT (r=0.48), HbA1c (r=0.40), Insulin sensitivity index (r=-0.57) and markers of adiposity (BMI, r=0.45; fat mass, r= 0.50; liver fat%, r=0.41) (p<0.001). Keratin type I cytoskeletal 18 (CK-18) and L-xylulose reductase levels were already increased at baseline in subjects who one-year later developed T2DM compared to subjects who reversed to normoglycemia or maintained the prediabetic state, respectively. The concentrations of these two proteins correlated strongly with AST and ALT (L-xylulose, r= 0.70, CK-18, r= 0.59).

Conclusion The current analysis has identified plasma proteins associated with glycemic state and metabolic traits. The role of these proteins as metabolic biomarkers or contributors in glucose homeostasis should be further assessed in future studies.

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Artikel online veröffentlicht:
02. Mai 2023