Department of Internal Medicine and Endocrinology (MEA) and Medical Research Laboratory, Aarhus University Hospital, Aarhus C, Denmark.
Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus N, Denmark.
J Diabetes Investig. 2019 Jan;10(1):67-72. doi: 10.1111/jdi.12869. Epub 2018 Jun 30.
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.
糖尿病酮症酸中毒（DKA）与炎症和脂肪分解增加有关。巨噬细胞活化标志物可溶性 CD163（sCD163）与肥胖、非酒精性脂肪性肝病和 2 型糖尿病有关。我们旨在研究在轻度 DKA 期间，1 型糖尿病患者的 sCD163 是否与脂肪分解的关键因素相关。
我们在两次研究中调查了 9 例 1 型糖尿病患者：（i）在正常血糖控制条件下和盐水推注时；（ii）通过给予脂多糖联合胰岛素剥夺诱导高血糖酮症时。使用血液样本、间接热量测定法、棕榈酸示踪剂和脂肪组织活检来研究脂质代谢。
我们观察到在脂多糖暴露后血浆 sCD163 水平显著升高（P < 0.001）。sCD163 浓度与游离脂肪酸、棕榈酸出现率和脂质氧化率的血浆浓度呈正相关，与脂肪组织中 G0/G1 切换 2 基因信使核糖核酸含量呈负相关（P < 0.01 均为）。此外，sCD163 水平与皮质醇、胰高血糖素、肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-10 的血浆峰值浓度呈正相关（P < 0.01 均为）。以前已经发表了关于脂肪分解和炎症的数据。
用 sCD163 评估的巨噬细胞活化在 DKA 中可能起重要作用，因为它与 DKA 初始阶段的重要脂质代谢成分（包括游离脂肪酸、棕榈酸、脂质氧化、G0/G1 切换 2 基因和促炎细胞因子）密切相关。这些结果是新颖的，并为 DKA 领域增添了重要知识。
