## 3 Discussion  
The global rise of diabetes and its accompanying, progressive micro- and macrovascular complications warrant the need for therapeutic measures which can alleviate or halt the progression of complications, resulting in increased capacity to manage diabetes. Chronic low-grade inflammation is a common feature found in people with diabetes, and may be a driver for the progressive nature of diabetes complications [4]. The anti-inflammatory myeloid scavenger receptor CD163 has been reported to be decreased in people with diabetes complications [5]. Using RNA-seq and mass cytometry, we observed that both RNA and phenotypic profiles of circulating CD163+ monocytes were different in those with diabetes and complications compared to those without complications. In the context of complications, we reported enriched centrosome cycle genes and up-regulated miRNAs implicated in apoptosis, suggesting a decreased number of anti-inflammatory CD163+ monocytes (Figure 6). Additionally, in individuals with diabetes-related complications, CD163+ monocytes exhibit reduced abilities for cell recruitment and trans-endothelial migration, along with dysregulated activation of their adaptive immune system (Figure 6). These findings suggest that the anti-inflammatory nature and functionality of the CD163+ monocytes are diminished in cases of diabetes complications, and this may reduce the potential to resolve inflammation. Deep RNA profiling of circulating CD163+ monocytes in our study revealed that in those with diabetes-related complications, the genes associated with the'regulation of centrosome cycle' were up-regulated and enriched. [PERSON] and colleagues reported enriched centrosome amplification within the peripheral blood mononuclear cells of individuals with type 2 diabetes, although the complication status of the participants was unknown [11]. The centrosome and its associated components determine the geometry of microtubule arrays throughout the cell cycle, which influence cell shape, polarity, motility, chromosome segregation, and cell division [12]. Dysregulation in the centrosome cycle can implicate cellular apoptosis [13], which would correspond with the up-regulated microRNAs _MIR23A_ and _MIR27A_ found in CD163+ cells in this study, as they also contribute to increased cellular apoptosis [14,15]. Our finding of potentially increased cellular apoptosis of circulating CD163+ monocytes would explain the previous finding of decreased circulating peripheral CD163+ monocytes in individuals with diabetes-related complications [5]. The reduced presence of anti-inflammatory CD163+ monocytes in the systemic circulation would support the notion of a prolonged inflammatory state in the systemic environment of individuals with diabetes-related complications (Figure 6). A significantly distinct functional profile of CD163+ monocytes was observed in this study between individuals who have diabetes with and without complications. Specifically, genes and cell surface markers involved in trans-endothelial migration and the recruitment of CD163+ monocytes were significantly suppressed and the expression of chemokine receptors _CX3 CR1_, _CXCL7_ (_PPBP_), and CCR5 were down-regulated in those with diabetes complications. When coupled with the decreased proportion of the adhesion markers CD11b, CD11c, and CD31, this would be indicative of the reduced ability of CD163+ monocytes to adhere to the endothelium of vasculature and extravasate into local tissues (Figure 6). Furthermore, the association between the up-regulated gene _MMP24_ and the down-regulated protein CD31, as discovered by the interaction network analysis, suggests MMP24 may be involved in reducing the cell surface expression of CD31, possibly through mediating ectodomain shedding, based on previous findings reported in animal studies of retinopathy in diabetes [16].