Soluble CD163 correlates with lipid metabolic adaptations in type 1 diabetes patients during ketoacidosis

Diabetic ketoacidosis (DKA) is associated with inflammation and increased lipolysis. The macrophage activation marker, soluble CD163 (sCD163), is associated with obesity, non-alcoholic fatty liver disease and type 2 diabetes. We aimed to investigate whether sCD163 correlates with key elements of lipolysis in type 1 diabetes patients during mild DKA.

We investigated nine patients with type 1 diabetes twice during: (i) euglycemic control conditions and a bolus of saline; and (ii) hyperglycemic ketotic conditions induced by lipopolysaccharide administration combined with insulin deprivation. Blood samples, indirect calorimetry, palmitate tracer and adipose tissue biopsies were used to investigate lipid metabolism.

We observed a significant increase in plasma sCD163 levels after lipopolysaccharide exposure (P < 0.001). Concentrations of sCD163 were positively correlated with plasma concentrations of free fatty acids, palmitate rate of appearance and lipid oxidation rates, and negatively correlated to the expression of G0/G1 switch 2 gene messenger ribonucleic acid content in adipose tissue (P < 0.01 for all). Furthermore, sCD163 levels correlated positively with plasma peak concentrations of cortisol, glucagon, tumor necrosis factor-α, interleukin-6 and interleukin-10 (P < 0.01 for all). Data on lipolysis and inflammation have previously been published.

Macrophage activation assessed by sCD163 might play an important role in DKA, as it correlates strongly with important components of lipid metabolism including free fatty acids, palmitate, lipid oxidation, G0/G1 switch 2 gene and pro-inflammatory cytokines during initial steps of DKA. These results are novel and add important knowledge to the field of DKA.