Aslan Ibrahim, Çeker Tuğçe, Ustabaş Tayfun, Zorlu Vuslat, Yılmaz Çağatay, Aslan Mutay
Endocrinology Clinic, Antalya Research and Education Hospital, The University of Health Sciences, Antalya 07000, Turkey.
Department of Medical Biochemistry, Akdeniz University Medical Faculty, Antalya 07000, Turkey.
Pathophysiology. 2025 Jun 26;32(3):29. doi: 10.3390/pathophysiology32030029.
: Diabetic ketoacidosis (DKA) is an acute and severe complication of diabetes mellitus, marked by hyperglycemia, ketosis, and acidosis. It is associated with significant metabolic and inflammatory adjustments that can impact multiple biochemical pathways. This study aimed to determine the serum sphingolipid profile in DKA and investigate its relationship with neutral sphingomyelinase (N-SMase), pro-inflammatory cytokines, β-hydroxybutyrate (β-OHB), and lactate levels. : Thirty-three participants were divided into three groups: control (BMI ≤ 30, no health issues), obese (BMI > 30), and DKA (BMI ≤ 30). Sphingomyelins (16:0-24:0 SMs) and ceramides (C16-C24 CERs) were measured using ultra-fast liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). N-SMase, interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) levels were assessed by enzyme-linked immunosorbent assay. Evaluations were done in the DKA group before and after standard clinical treatment for DKA (post-DKA group), which included intravenous insulin therapy, fluid resuscitation, and electrolyte replacement, as per established clinical guidelines. : β-OHB levels were significantly higher in the DKA group than in the control, obese, and post-DKA groups. Although β-OHB levels decreased in the post-DKA group, they remained elevated compared to the control and obese groups. Lactate levels were also higher in the DKA group, with a significant decrease in the post-DKA group. TNF-α and IL-1β were higher in the obese group compared to control and DKA groups, and TNF-α decreased significantly in the post-DKA group compared to DKA. N-SMase, 16:0-18:0 SMs, and C18-C24 CER levels were lower in the DKA and post-DKA groups compared to obese and control groups. Serum β-OHB and lactate levels were significantly correlated with S1P, total CER, total SM, and N-SMase values. : The study reveals significant metabolic and inflammatory differences in DKA and post-DKA states, suggesting a relationship between sphingolipids, N-SMase, and these alterations, which could offer insights into DKA pathophysiology and therapeutic targets.
糖尿病酮症酸中毒（DKA）是糖尿病的一种急性严重并发症，其特征为高血糖、酮症和酸中毒。它与显著的代谢和炎症调节有关，可影响多种生化途径。本研究旨在确定DKA患者的血清鞘脂谱，并研究其与中性鞘磷脂酶（N-SMase）、促炎细胞因子、β-羟基丁酸（β-OHB）和乳酸水平的关系。33名参与者被分为三组：对照组（BMI≤30，无健康问题）、肥胖组（BMI>30）和DKA组（BMI≤30）。使用超快速液相色谱结合串联质谱（LC-MS/MS）测定鞘磷脂（16:0 - 24:0 SMs）和神经酰胺（C16 - C24 CERs）。通过酶联免疫吸附测定法评估N-SMase、白细胞介素1β（IL-1β）和肿瘤坏死因子α（TNF-α）水平。在DKA组接受DKA标准临床治疗前后（DKA后组）进行评估，治疗包括静脉注射胰岛素、液体复苏和电解质补充，均按照既定临床指南进行。DKA组的β-OHB水平显著高于对照组、肥胖组和DKA后组。虽然DKA后组的β-OHB水平有所下降，但与对照组和肥胖组相比仍处于较高水平。DKA组的乳酸水平也较高，DKA后组显著下降。肥胖组的TNF-α和IL-1β水平高于对照组和DKA组，与DKA组相比，DKA后组的TNF-α显著下降。与肥胖组和对照组相比，DKA组和DKA后组的N-SMase、16:0 - 18:0 SMs和C18 - C24 CER水平较低。血清β-OHB和乳酸水平与S1P、总CER、总SM和N-SMase值显著相关。该研究揭示了DKA和DKA后状态存在显著的代谢和炎症差异，表明鞘脂、N-SMase与这些改变之间存在关联，这可能为DKA的病理生理学和治疗靶点提供见解。
