## 2 Results
### Gene-Protein Interaction Network  
A gene-protein interaction network was created, combining the 75 GOIs with the significantly different cell surface markers including CCR5, CD11b, CD11c, CD31, CD39, CD86, and CD68. This analysis revealed a network of 32 nodes in which CD11b and _TLR4_ were the 'hub-nodes' with 16 edges, each connected to 16 nodes (Figure 5). CD86, with \begin{table}
\begin{tabular}{c c c c c c} \hline \hline \multirow{2}{*}{**Function**} & **Positive \% of CD163+** & **D\({}^{+\text{Comps}}\) (\(\boldsymbol{u}\) = 6)** & **D\({}^{-\text{Comps}}\) (\(\boldsymbol{u}\) = 6)** & **Fold Change** & \(p\) **Value** \\ \hline \multirow{2}{*}{Activation} & CD282 & \multirow{2}{*}{0.4 (0.1–3.7)} & \multirow{2}{*}{0.45 (0.2–0.8)} & \multirow{2}{*}{\(-0.1\)} & \multirow{2}{*}{ns} \\  & (TLR2) & & & & \\  & CD284 & & & & \\  & (TLR4) & & & & \\  & CD38 & & & & \\ \hline \multirow{4}{*}{Chemokine receptors} & CD192 & \multirow{2}{*}{2.6 (1.7–4.8)} & \multirow{2}{*}{0.9 (0.5–3.6)} & \multirow{2}{*}{2.6} & \multirow{2}{*}{ns} \\  & (CCR2) & & & & \\  & CD195 & \multirow{2}{*}{59.6} & \multirow{2}{*}{78.4} & \multirow{2}{*}{\(-1.3\)} & \multirow{2}{*}{\(p<0.05\)} \\  & (CCR5) & & & & \\  & CX3 CR1 & & & & \\  & CXR3 & & & & \\ \hline \multirow{4}{*}{Adhesion and migration} & CD11b & \multirow{2}{*}{12.1} & \multirow{2}{*}{54.4} & \multirow{2}{*}{\(-4.5\)} & \multirow{2}{*}{\(p<0.05\)} \\  & (7.8–22.2) & & & & \\  & CD11c & \multirow{2}{*}{27.8 \(\pm\) 11.5} & 60.1 \(\pm\) 2.3 & \multirow{2}{*}{\(-2.2\)} & \multirow{2}{*}{\(p<0.05\)} \\  & CD31 & & & & \\  & (PECAM-1) & & & & \\  & (18.8–52.3) & & & & \\ \hline \multirow{4}{*}{Immun regulation} & CD39 & \multirow{2}{*}{4.2 \(\pm\) 2.4} & \multirow{2}{*}{13.0 \(\pm\) 6.8} & \multirow{2}{*}{\(-3.1\)} & \multirow{2}{*}{\(p<0.05\)} \\  & CD73 & & & & \\  & CD80 & & & & \\  & CD86 & & & & \\  & CD206 & & & & \\  & (0.05–1.05) & & & & \\ \hline \multirow{4}{*}{Phagocytosis and clearance} & \multirow{2}{*}{CD36} & \multirow{2}{*}{99.2} & \multirow{2}{*}{92.0} & \multirow{2}{*}{1.1} & \multirow{2}{*}{ns} \\  & & (82.2–99.6) & & & \\ \cline{1-1}  & & 97.3 & 98.8 & & \\ \cline{1-1}  & & (93.7–98.2) & & & \\ \hline \hline \end{tabular}  
* Results are expressed as mean \(\pm\) SD or median with interquartile range (IQR) or proportion. Folder changes were expressed as D\({}^{+\text{Comps}}\) compared to D\({}^{-\text{Comps}}\) and significance accepted at \(p\) < 0.05. No significance indicated by ns.  
\end{table} 
Table 2: Functional phenotyping of CD163+ monocytes in individuals with diabetes with or without complications. 14 edges connected to 14 nodes, was found to be down-regulated at both the gene and cell surface levels (Figure 5). The 'hub-node' CD11b was connected to genes including _TLR4_, _PPBP_, _PTGS2_, and _ZAP70_, as well as various cell surface markers. _TLR4_ was linked to genes _TRPV1_, _NFKB2_, _TRAF1_, _CD200R1_, _CX3 CR1_, and _PPBP_, and surface markers CD86, CD68, CD31, and CD39 (Figure 5). CD86 was in connection with genes _CD244_, _PTGS2_, and _ZAP70_, and cell surface markers CD31 and CD39. Figure 5: Gene–protein interactions network illustrating the largest connected network of ‘genes of interest’, combined with significantly different cell surface markers in CD163+ monocytes between individuals with long-term diabetes and complications (D\({}^{+\text{Comps}}\)) and those without complications (D\({}^{-\text{Comps}}\)). Genes were considered significantly down- or up-regulated if the fold change was \(\geq\)1.5 (BHp < 0.05). Proteins were considered significantly different at \(p<0.05\). The color of the circular node indicates the intensity of the fold change, confirmed by the legend below. The sectioned multicolor outline of each node indicates the involvement of respective genes, with the top five most enriched GO categories including biological processes. Yellow star indicates genes, whereas red star indicates protein.