Type 1 diabetes mellitus (T1DM) does not affect whole blood responses to alginate-based microspheres despite plasma...

Encapsulation of insulin-producing cells holds significant therapeutic potential for treating type 1 diabetes (T1DM). The impact of diabetic conditions on host responses is not well understood. This study is the first to compare ex-vivo whole blood responses to alginate microbeads in T1DM subjects versus healthy controls. Nineteen T1DM and 27 healthy controls were included. Alginate microbeads varying in guluronic acid content (68 % and 47 % G), sulfated alginate/alginate ratios (10/90 and 20/80), or containing poly-L-lysine were characterised regarding activation of coagulation, complement, and inflammatory cytokine release in whole blood. Responses to heat-killed microbes (E. coli, S. pneumoniae, M. tuberculosis, and C. albicans) and immune agonists (TLR ligands, T-cell stimulant, and Dectin ligand) were also compared. NMR spectroscopy identified 40 altered lipoproteins and metabolites in plasma in T1DM vs. controls. However, whole blood responses were strikingly similar, indicating that metabolic alterations in T1DM are not accompanied by differences in inflammatory capacity. When merging all subjects, PCA clustered microbead responses into three groups of alginates, sulfated alginates, and poly-L-lysine-coated alginate (AP), respectively. Pairwise comparison by multiple t-tests identified significant changes in inflammatory mediators between the main groups; alginate microbeads differentially induced 25 out of 29 mediators compared to AP microbeads and 18 mediators compared to sulfated alginate microbeads. Alginate microbeads with distinct guluronic acid content (68 % vs 47 % G) revealed no significant differences. These findings indicate that the material properties are the most important determinants of the host inflammatory responses in blood, which are not changed in well-controlled T1DM.