Pathophysiology, Volume 32, Issue 3 (September 2025) – 20 articles

Background/Objectives: The pathognomonic feature of systemic lupus erythematosus (SLE) is the formation of antibodies to double-stranded DNA (anti-dsDNA Abs). Cell-free DNA (cfDNA) has been suggested as one of the antigens for the generation of anti-dsDNA Abs, but the temporal changes in these biomarkers are not clear. In this study, the association of dynamic changes in total cfDNA and anti-dsDNA Abs levels in blood plasma during disease progression in a murine model of pristane-induced SLE was examined. Methods: The experimental group consisted of 12 BALB/c pristane-immunized mice; the control group included 8 PBS-treated mice. Blood samples were collected six times during the 38-week study (2 weeks before and 8, 14, 22, 28, and 36 weeks after immunization). Total cfDNA and anti-dsDNA Abs levels were determined at each time point. Results: Pristane-immunized mice showed a significant increase in the concentration of anti-dsDNA Abs. A 14-week delay in the formation of anti-dsDNA Abs was observed after an increase in the concentration of cfDNA in the experimental and control groups. Anti-dsDNA Abs and total cfDNA levels did not correlate at specific time points, but the change in cfDNA concentration from week 14 to week 28 was inversely correlated with the change in the anti-dsDNA Abs level over the same time period (R = −0.71, p = 0.009), i.e., the more the anti-dsDNA Abs level increased, the more the cfDNA concentration decreased. A direct correlation was shown between the increase in body weight of pristane-immunized mice and the increase in total cfDNA concentration in the blood from week 0 to week 14 (R = 0.6, p = 0.04). Conclusions: These findings demonstrate the dynamic nature of cfDNA and anti-dsDNA Abs levels and reciprocal dynamics of these markers in a pristane-induced mouse model of SLE. Full article

Autoimmune pulmonary alveolar proteinosis (aPAP) is characterized by the accumulation of phospholipids and surfactant proteins in the peripheral air spaces due to alveolar macrophage dysfunction caused by anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (GMAb). Hypersensitivity pneumonitis (HP) is a granulomatous lung disease associated with GM-CSF. In this report, we evaluated serial changes in serum GMAb levels in a 67-year-old male current smoker with HP and aPAP and examined their correlation with HP disease activity. GMAb levels increased at HP onset and decreased after HP remission with oral prednisolone therapy. After the first remission, the patient experienced three relapses and remissions. Although GMAb levels were not evaluated for all HP relapses and remissions, GMAb levels increased at one relapse but decreased at two remissions induced by the oral prednisolone therapy. Pulmonary fibrosis progressed, and the patient died of pneumonia. GMAb was at its almost normal levels at 8 months before the onset of pneumonia. We hypothesized that GMAbs may have been induced to improve HP through neutralizing GM-CSF. Although the hypothesis needs to be confirmed in additional patients, serial measurement of GMAb may be useful for a better understanding of the pathophysiology and deciding the appropriate treatment for HP with aPAP. Full article

Background: Fatigue has been associated with poorer quality of life and increased morbidity in multiple clinical fields. Patients with autonomic dysfunction have been found to experience poorer physiological health, as well as having an increased risk of comorbidity and all-cause mortality. Heart rate variability (HRV) has been documented as a validated tool to assess autonomic function in clinical practice. The aim of this systematic review was to understand the relationship between fatigue and HRV in different medical populations. Methods: A systematic search was conducted in MEDLINE via Web of Science and Scopus. Results: A total of seventeen articles were identified for inclusion. Patients with Chronic Fatigue Syndrome were the most investigated population (n = 7), followed by cancer (n = 4) and Multiple Sclerosis (n = 4). The most implemented fatigue measure was the Multidimension Fatigue Inventory Scale used in four studies and HRV was monitored by electrocardiogram in nine studies. The most recorded and analysed domain for HRV was the frequency parameters. A significant association between increased subjective fatigue and imbalanced metrics of HRV (p < 0.05) was identified in fourteen articles. However, results from this review were heterogenous partly owing to the inconsistency with the instruments implemented to monitor HRV and measure fatigue. Additionally, only a small number of medical conditions were investigated, and the patients were predominately older adults (mean age 43.2) and women (64%). Conclusions: Despite these discrepancies, the reviewed evidence suggests that a rise in sympathetic activity and reduced parasympathetic tone are associated with an increased perception of fatigue in medical populations. Full article

Background: Cardiovascular disease (CVD) remains the leading cause of death in Europe. Despite medical advancements, modifiable risk factors—such as obesity, smoking, and physical inactivity—continue to rise, especially in high-demand professional groups like military personnel. The updated SCORE2 model offers broader assessment capabilities compared to the traditional Pol-SCORE system used in Poland. This study aimed to assess and compare cardiovascular risk using both models and evaluate self-awareness of cardiovascular risk factors among military and civilian employees. Methods: The study included military personnel and civilian defense employees who completed a health-related questionnaire and underwent clinical evaluation, including blood pressure measurement and lipid profiling. Cardiovascular risk was assessed using both Pol-SCORE (fatal events only) and SCORE2 (fatal and non-fatal events). Statistical analysis was conducted using standard parametric and nonparametric methods. Results: SCORE2 classified significantly more individuals into high or very high cardiovascular risk categories than Pol-SCORE. Differences were especially pronounced among women and civilians. Elevated blood pressure, overweight, obesity, tobacco use, and stress were commonly observed. Despite a high level of awareness about prevention, regular participation in screening was low, and many respondents underestimated their health risk, indicating the presence of unrecognized or underestimated risk. Conclusions: SCORE2 proves to be a more sensitive and comprehensive tool for cardiovascular risk evaluation. The findings emphasize the urgent need for targeted prevention strategies and health education, especially in high-risk occupational groups such as military personnel. Full article

Tenascin-C (TNC) is an extracellular matrix (ECM) protein with key roles in various biological processes, such as embryonic development and tissue regeneration. However, its deregulated expression can contribute to pathological responses, promoting chronic inflammation, fibrosis, or tumor progression. It belongs to the tenascin family, a class of extracellular proteins that interfere with cellular events in both physiological and pathological contexts, interacting specifically with cells and other components of the ECM. TNC has emerged as a key player in the pathogenesis of chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease (COPD), lung cancer (LC), pulmonary hypertension (PH), and idiopathic pulmonary fibrosis (IPF). The influence of TNC on cellular responses, which is mediated by precise interactions with cellular receptors and ligands, triggers complex intracellular signaling cascades associated with the inflammatory response, fibrosis, and tumorigenesis in these CRDs. This review synthesizes recent evidence highlighting the multifaceted roles and underlying mechanisms of TNC in the context of these CRDs. Full article

Neurodegenerative diseases are a group of disorders characterized by the progressive deterioration of the structure and function of central nervous system neurons and include, among others, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson’s (PD), Alzheimer’s (AD), and Huntington’s (HD) diseases. And while all these diseases seem to have different genetic and environmental components, growing evidence shows that they share common underlying pathological features such as increased neuroinflammation and excessive oxidative stress. RAGE, the receptor for advanced glycation end-products, is a signal transduction receptor, and its activation triggers an increase in proinflammatory molecules, oxidative stressors, and cytokines. Diaph1, protein diaphanous homolog 1, is an actin modulator and an intracellular ligand of RAGE. Studies demonstrated that RAGE and Diaph1 act together, and their downstream signaling pathways play a role in neurodegeneration. Here, based on current evidence and our own research, we provide an overview of the RAGE–Diaph1 signaling and discuss the therapeutic potential of targeted therapy aimed at RAGE–Diaph1 signaling inhibition in the prevention and treatment of neurodegenerative diseases. Full article

Background/Objectives: Methamphetamine (METH), a potent psychostimulant, exerts harmful effects on the vascular system by promoting oxidative stress, inflammation, and endothelial injury. While its impact on the blood–brain barrier is well documented, its influence on the retinal microvasculature remains less understood. This study investigated the effects of METH on syndecan-1 expression and endothelial function in primary rat retinal microvascular endothelial cells (RRMECs) and isolated ophthalmic arteries. Methods: We assessed METH-induced changes in mRNA and protein expression levels of syndecan-1, matrix metalloproteinase (MMP)-2, and MMP-9. Endothelial function was evaluated using scratch migration assays and trans-endothelial electrical resistance (TEER) measurements. The mechanistic involvement of MMP-9 and trace amine-associated receptor 1 (TAAR-1), a known receptor for METH, was examined using selective pharmacological inhibitors. Results: METH exposure significantly decreased syndecan-1 expression and increased MMP-9 levels. These changes were accompanied by impaired endothelial migration and reduced TEER in RRMECs. Similar findings were confirmed in cultured ophthalmic arteries, reinforcing the translational relevance of our in vitro results. Inhibition of MMPs restored syndecan-1 expression and rescued endothelial function. Furthermore, TAAR-1 antagonism protected against syndecan-1 degradation, reduced MMP-9 upregulation, and improved endothelial migration and barrier resistance. Conclusions: Our findings suggest that METH induces loss of syndecan-1 and retinal vascular integrity by promoting TAAR-1–mediated MMP-9 upregulation. Targeting the TAAR-1/MMP-9 axis may offer a promising therapeutic strategy for preventing METH-induced microvascular damage in the retina. Full article

Background/Objectives: Post-stroke cognitive impairment significantly impacts long-term functional outcomes, particularly in instrumental activities of daily living (IADLs). Working memory training (WMT) has emerged as a potential cognitive rehabilitation strategy; however, its transfer to real-world functionality remains unclear. This study evaluated whether adaptive computerized WMT enhances IADLs performance compared to a non-adaptive control condition in chronic stroke survivors. Methods: A single-blind, randomized controlled trial was conducted with 50 adults aged 50–79 years, ≥12 months post-ischemic stroke, and diagnosed with a mild neurocognitive disorder. Participants were randomized to adaptive WMT or non-adaptive cognitive training, each completing 25 home-based sessions over 12 weeks via a standardized online platform. Primary outcomes included the Lawton and Brody IADL Scale and the Working Memory Questionnaire (WMQ); secondary outcomes included the Working Memory Index (WMI) from the WAIS-IV. Analyses included frequentist and Bayesian methods. Results: Both groups showed significant pre–post improvements in IADL independence and WMI (p < 0.05; BF₁₀ > 10), with no significant between-group differences on overall IADL outcomes. The adaptive WMT group demonstrated specific gains in WMQ—Storing (p = 0.033; BF₁₀ = 3.83), while the control group improved in WMQ—Attention and IADL—Assistance Required (p = 0.004–0.035; BF₁₀ > 6). Bayesian ANOVA indicated that these effects were primarily driven by the interventions, with minimal influence from depressive symptoms or global cognition. Conclusions: Adaptive WMT yielded domain-specific cognitive benefits but did not enhance IADL performance beyond non-adaptive training. These findings highlight the limited far transfer of WMT and the importance of designing ecologically valid, multimodal rehabilitation strategies post-stroke. Full article

Background: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, specifically its Main Protease (M^pro), in accelerating insulin resistance and metabolic dysfunction in HepG2 cells in vitro. Methods: HepG2 cells were treated with varying concentrations of M^pro (2.5, 5, 10, 20, 40, 80, and 160 nmol/mL) for 24 h to assess cytotoxicity and glucose uptake. Based on initial findings, subsequent assays focused on higher concentrations (40, 80, and 160 nmol/mL). The effects of M^pro on cell viability, protein kinase B (AKT) expression, matrix metallopeptidase-1 (MMP1), dipeptidyl peptidase 4 (DPP4), interleukin-6 (IL-6) expression, and lipid peroxidation were investigated. Results: Our findings reveal that the SARS-CoV-2 M^pro treatment led to a concentration-dependent reduction in glucose uptake in HepG2 cells. Additionally, the M^pro treatment was associated with reduced insulin-stimulated AKT activation, particularly at higher concentrations. Inflammatory markers such as IL-6 were elevated in the extracellular medium, while DPP4 expression was decreased. However, extracellular soluble DPP4 (sDPP4) levels did not show a significant change. Despite these changes, cell viability remained relatively unaffected, suggesting that the HepG2 cells were able to maintain overall metabolic functions under M^pro exposure. Conclusions: This study demonstrated the concentration-dependent impairment of hepatic glucose metabolism, insulin signaling, and inflammatory pathways in HepG2 cells acutely exposed to the SARS-CoV-2 M^pro. These findings warrant further investigation to explore the long-term metabolic effects of SARS-CoV-2 and its proteases in the liver and to develop potential therapeutic approaches for post-viral metabolic complications. Full article

Secondary lymphoma of the prostate is described as the involvement of the prostate gland by lymphomatous spread from a primary site. This condition is exceedingly rare and often presents diagnostic and therapeutic challenges. The symptoms often mimic those of benign prostatic hyperplasia or prostate cancer, including LUTS (lower urinary tract symptoms) and even complete urinary retention. Here, we present a rare case of a 62-year-old male patient undergoing chemotherapy for stage IV mantle cell stomach lymphoma and subsequently secondary prostatic involvement. The patient presented with complete urinary retention, accompanied by biochemical (PSA = 11.7 ng/mL) and imaging (Magnetic Resonance Imaging-PIRADS V lesion) suspicion for prostate cancer. Histopathologic analysis of the MRI-targeted prostate fusion biopsy revealed secondary prostatic lymphoma. The chosen treatment was transurethral resection of the prostate (TUR-P) for relief of symptoms, which significantly improved urinary function (postoperative IPSS = 5 and Qmax = 17 mL/s). This case underscores the importance of considering prostatic lymphoma in the differential diagnosis of bladder outlet obstruction, especially in patients with a known lymphoma history. This report also provides a focused review of the literature on secondary prostatic lymphoma, highlighting the diagnostic challenges, treatment options, and clinical outcomes. Full article

Thyroid hormones play a crucial role in regulating metabolism and cardiovascular function, with even mild dysfunction—such as subclinical hypothyroidism—negatively impacting heart health. While previous studies have confirmed the effects of iodine, selenium, and vitamin D on thyroid regulation and inflammation, the combined role of these nutrients in reducing cardiovascular disease (CVD) risk in autoimmune thyroid disorders remains insufficiently understood. This review explores the influence of specific micronutrients—including selenium, iodine, and zinc—and dietary patterns, particularly the Mediterranean diet, on the pathophysiology of hypothyroidism and Hashimoto’s thyroiditis. We introduce a novel framework that integrates emerging data on sex-specific micronutrient interactions and nutritional immunomodulation. Unlike the existing literature, this review introduces original hypotheses related to sex-specific nutritional immunomodulation and proposes a novel framework for micronutrient-driven dietary intervention in Hashimoto’s thyroiditis. Full article

Background/Objectives: Osteonecrosis of the femoral head (ONFH) is a common condition in hip surgery, which is characterized by the death of bone cells due to disruption of the blood supply and ultimately irreversible destruction of the hip joint. As a result of the COVID-19 pandemic, a significant increase in the incidence of ONFH has been identified. To better understand the pathogenesis of ONFH in the context of COVID-19, our research aimed to determine pathomorphological changes in articular tissues specific to post-COVID-19 ONFH. Methods: Using morphological, morphometric, and statistical methods, the femoral heads after hip arthroplasty were retrospectively studied in patients with post-COVID-19 ONFH (n = 41) compared to a non-COVID-19 group of patients (n = 47). Results: Our results revealed that the key morphofunctional biomarkers of post-COVID-19 ONFH were clusters of mast cells, extensive areas of fibrosis, numerous arterial and venous thrombi, and giant cell granulomas. The potential relationship of those morphological features with the action of the SARS-CoV-2 coronavirus was discussed. Conclusions: Mast cells have been proposed as the leading players that may trigger the main molecular and cellular mechanisms in the development of post-COVID-19 ONFH and can be considered a diagnostic sign of the disease. Full article

Fetal alcohol spectrum disorder (FASD) is a preventable cause of developmental disabilities linked to prenatal alcohol exposure (PAE). Congenital heart defects (CHDs) are frequently observed in FASD, with a notable association between PAE and dextro-type transposition of the great arteries (d-TGA). A potential pathogenetic mechanism of d-TGA in FASD, involving retinoic acid (RA) deficiency due to the interference of ethanol with RA biosynthesis, is proposed. Further investigation is required to understand the timing and impact of alcohol exposure on congenital anomalies, particularly in the context of CHDs. Full article

Despite the growing morbidity associated with alcohol use disorder (AUD), current FDA-approved therapeutics fail to adequately address the condition. This is in part due to the complex systemic effects of ethanol (EtOH), which have particularly negative consequences on the gut–liver–brain axis. Importantly, two systemic mechanisms underlying the progression of AUD remain underemphasized in therapeutic development: thiamine deficiency and neuroinflammation. Alcohol-induced thiamine deficiency leads to reduced activity of key metabolic enzymes, thereby resulting in energy deficits, oxidative stress, and severe clinical implications. EtOH also activates TLR4 and NLRP3, both of which play critical roles in the regulation of neuroimmune responses. While research directly investigating the relationship between thiamine deficiency and neuroinflammation is still in its early stages, our review highlights the emerging connections between these two seemingly distinct pathomechanisms. Additionally, potential therapeutic approaches and targets for addressing AUD at a systemic level are discussed. Full article

Renal function refers to the combined actions of the glomerulus and tubular system to achieve homeostasis in bodily fluids. While the glomerulus is essential in the first step of urine formation through a coordinated filtration mechanism, the tubular system carries out active mechanisms of secretion and reabsorption of solutes and proteins using specific transporters in the epithelial cells. The assessment of renal function usually focuses on glomerular function, so the tubular function is often underestimated as a fundamental part of daily clinical practice. Therefore, it is essential to properly understand the tubular physiological mechanisms and their clinical association with prevalent human pathologies. This review discusses the primary solutes handled by the kidneys, including glucose, amino acids, sodium, potassium, calcium, phosphate, citrate, magnesium and uric acid. Additionally, it emphasizes the significance of physicochemical characteristics of urine, such as pH and osmolarity. The use of a concise methodology for the comprehensive assessment of urine should be strengthened in the basic training of nephrologists when dealing with problems such as water and electrolyte balance disorders, acid-base disorders, and harmful effects of commonly used drugs such as chemotherapy, antibiotics, or diuretics to avoid isolated replacement of the solute without carrying out comprehensive approaches, which can lead to potentially severe complications. Full article

Background: This study investigated the impact of crack cocaine smoke exposure on the submandibular salivary gland of Wistar rats. Methods: The animals were distributed into four groups: control (CTRL); 25 mg exposure (CK25); 50 mg exposure (CK50); and 100 mg exposure (CK100). The animals were exposed to crack cocaine smoke once a day for five consecutive days. Results: Exposure to crack cocaine smoke-induced histopathological changes in submandibular salivary glands in all groups under exposure. The immunohistochemical analysis demonstrates that exposure to crack cocaine smoke led to an increase in BCL-2 and P16 expression in all groups exposed to crack cocaine (p < 0.05). The analysis of Ki-67 expression revealed a significant increase in immunoreactive cells across all exposure groups (p < 0.05). Although MYD88 expression was observed in all crack cocaine-exposed groups, only the group treated with the highest dose (100 mg) exhibited a statistically significant increase compared to the control group (p < 0.05). Conclusions: In summary, this study demonstrates that exposure to crack cocaine smoke-induced tissue degeneration in the submandibular salivary gland, increasing cellular senescence and promoting compensatory cell proliferation in Wistar rats. Full article

Amyloidosis, often referred to as “the great imitator”, is a condition characterized by the abnormal deposition of amyloid proteins in various tissues, potentially leading to organ dysfunction. When these deposits localize in the brain, they can disrupt neurological function and present with diverse clinical manifestations, making diagnosis particularly challenging. Cerebral amyloidosis is a rare entity that frequently mimics other neurological disorders, often resulting in significant delays in recognition and management. This case highlights the diagnostic challenge posed by cerebral amyloidosis and underscores its unique presentation. We present the case of a 76-year-old male with a history of rheumatoid arthritis (RA) who developed progressive right-sided weakness over several months. Three years prior, he experienced numbness on the right side of his face and upper limb. Initial imaging identified a small lesion in the left thalamic region, which was originally diagnosed as a glioma. However, due to the worsening of his clinical symptoms, further evaluation was warranted. Subsequent imaging revealed lesion growth, prompting a biopsy that ultimately confirmed the diagnosis of intracerebral amyloidoma. This case underscores the necessity of considering amyloidosis in the differential diagnosis of atypical neurological deficits, particularly in patients with systemic inflammatory conditions such as RA. The initial presentation of hemiparesis resembling a stroke, coupled with non-specific imaging findings and a prior misdiagnosis of glioma, highlights the complexity of cerebral amyloidosis. Only through brain biopsy was the definitive diagnosis established, emphasizing the need for improved diagnostic modalities to facilitate early detection. Further subtyping of amyloidosis, however, requires mass spectrometry-based proteomics or immunohistochemistry to accurately identify the specific amyloid protein involved. Clinicians should maintain a high index of suspicion for cerebral amyloidosis in patients with RA who present with progressive neurological deficits and atypical brain lesions. Early recognition and accurate diagnosis are essential to guiding appropriate management and improving patient outcomes. Full article

Background: Although immune complex formation is widely acknowledged as the etiological agent for the development of systemic lupus erythematosus, polyarteritis nodosa, reactive arthritis, etc., its roles in chronic hepatitis are less understood. This study aims to compare the immunohistochemistry profile of immune complex deposition in patients with chronic hepatitis B (CHB) and autoimmune hepatitis (AIH). Methods: Immunohistochemistry of C4d, a widely used marker for complement deposition was employed on liver biopsies from 72 and 15 patients with CHB and AIH, respectively. Statistical analysis was performed to analyze its prevalence and its association with a range of clinical and histological parameters. Results: Among the 15 AIH biopsies examined, C4d deposition was observed in 11 cases (73.3%), the majority of which showed a periportal staining pattern (10/11). In CHB, 61 (84.7%) of 72 cases tested positive for C4d, which did not differ significantly with that of AIH. While the periportal pattern was predominantly observed in CHB cases, positive staining in central veins, sinusoids, and hepatic parenchyma were also documented. In particular, C4d deposition is significantly associated with elevated serum ALT and liver inflammation in CHB. Of note, in specimens with a patchy parenchymal C4d staining pattern, a spatially correlated HBsAg IHC signal was observed in adjacent sections from the same tissue. Conclusions: These data suggest an involvement of immune complex-mediated immunopathy in autoimmune hepatitis and HBV-induced hepatitis. The positive intrahepatic C4d signal was associated with heightened liver inflammation. The colocalization of the C4d signal on hepatocytes with HBsAg strongly suggests a causal relationship between viral activity and complement deposition. These observations align with our recent evidence implicating the contribution of capsid–antibody complexes in the pathogenesis of CHB. Full article

Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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. Full article