Search Results (47)

Background/Objectives: Glioblastoma multiforme (GB) is an extremely aggressive tumor of the central nervous system, characterized by rapid growth, high invasiveness, and significant resistance to treatment. A growing body of data indicates that metabolic reprogramming of GB cells may be a therapeutic target, and that the ketogenic diet (KD)—by limiting glucose and inducing ketosis—may modulate tumor metabolism. The aim of this review was to provide a synthetic presentation of the current state of knowledge regarding the use of KD as an adjunctive therapy in the treatment of GB, with a particular focus on the mechanisms of action, safety, feasibility and results of clinical trials. Methods: The review was conducted in accordance with the Joanna Briggs Institute methodology and the PRISMA-ScR guidelines. A systematic search of PubMed, Scopus, EBSCO, Web of Science, Google Scholar, and Cochrane Library (1–10 April 2026) included studies on the use of KD in patients with GB. Full-text observational studies, randomised trials and reviews were included in the analysis. Data extraction was carried out according to the Population–Concept–Context (PCC) model. Results: Of the 26 publications identified, 12 met the inclusion criteria. Preclinical data consistently indicate that KD may reduce glycolysis, lower insulin and IGF-1 levels, increase oxidative stress in cancer cells, and modulate the inflammatory microenvironment. Clinical trials confirm the safety and feasibility of KD, as well as the ability to maintain stable ketosis. Preliminary data suggest potential metabolic benefits and improved quality of life, however, clinical efficacy remains inconclusive due to small trials, heterogeneous dietary protocols, and a lack of randomized trials. The variety of interventions used (classic KD; MCT-KD-Medium-chain triglyceride KD; KD-IF—KD and intermittent fasting) makes it difficult to compare the results. Conclusions: The KD represents a promising, low-toxic strategy to support the treatment of GB, based on biological basis. Available data indicate its safety and feasibility, but there is insufficient evidence to recommend its routine use in clinical practice. Large, multicenter, randomized trials with standardized dietary protocols and objective monitoring of metabolic parameters are needed to unambiguously assess the impact of KD on disease survival and progression. Full article

Fatty liver disease represents a major metabolic disorder affecting domestic animals worldwide, with significant implications for animal health, welfare, and agricultural productivity. Disrupted communication between mitochondria and other organelles—particularly the endoplasmic reticulum, lipid droplets, and lysosomes—plays a critical role in disease pathogenesis. This review synthesizes knowledge on inter-organellar communication across domestic animals, with emphasis on species-specific adaptations. We address the “Dairy Cow Paradox”—periparturient dairy cows develop severe hepatic steatosis (>30% liver fat), yet under sterile conditions, they have a higher threshold for progressing to sterile steatohepatitis compared to rodents and humans. However, it is critical to note that severe fatty liver in dairy cows is indeed associated with impaired autophagy, inflammation, and liver damage, particularly when accompanied by ketosis or concurrent infections, and 39% of transition cows exhibit moderate to severe lymphocytic hepatitis. We propose that the tolerance to severe steatosis in dairy cows arises from three adaptations: (1) attenuated innate immune sensing via the cGAS-STING pathway; (2) enhanced lipid buffering from perilipin 5 (PLIN5) with a hypothesized ruminant-specific Val152 substitution that may stabilize lipid droplet–mitochondria contacts; and (3) dampened calcium signaling due to ER–mitochondria membrane lipid raft rigidity, elevated inositol 1,4,5-trisphosphate receptor 2 (IP₃R2) expression, and reduced mitochondrial calcium uniporter (MCU) conductance. We contrast this with the inflammatory steatohepatitis common in rodent models driven by calcium overload and mitochondrial DNA (mtDNA) release, and glucocorticoid-mediated mitofusin 1 (MFN1) suppression, causing mitochondrial fragmentation in poultry. We identify critical knowledge gaps, including the need to define bovine and avian mitochondria-associated endoplasmic reticulum membrane (MAM) proteomes and spatially resolve hepatic zonal communication patterns. Targeting organellar communication hubs with nutraceuticals or pharmacological agents offers promising therapeutic strategies. Full article

Background: Dietary interventions in heart failure (HF) remain limited, with current guidance focused largely on sodium restriction. Ketone metabolism has emerged as a potential therapeutic target in HF, with ketone supplementation shown to improve cardiac function. However, there are currently no studies investigating factors affecting adherence to a ketogenic diet (KD) in HF. Aim: To explore the factors influencing adherence to a KD in patients with HF to inform future dietary interventions. Method: This qualitative study was embedded within the KETO-HF pilot randomised controlled trial, in which participants with HF with reduced ejection fraction undertook a 4-month KD. Consenting participants were invited to complete semi-structured interviews. Interviews were audio-recorded, deidentified and transcribed verbatim. Data were analysed using thematic analysis with a mixed inductive–deductive strategy. Results: Fifteen participants were interviewed. Facilitators of adherence were: (1) personal motivation and self-regulation; (2) improved well-being; (3) interpersonal support and; (4) adaptive strategies and improved nutritional literacy. Barriers included: (1) early-phase physiological and psychological challenges; (2) social and cultural friction; (3) competing family and work demands and; (4) limited availability of suitable foods, particularly difficulty managing social situations and dining out. Conclusions: Adherence to a KD in people with HF is shaped by a combination of individual and social factors. These findings highlight the need for improved education, support, and increased food options to optimise implementation of dietary ketosis in HF. Full article

Background: Prostate cancer (PCa) is the most commonly diagnosed malignancy in men and a leading cause of cancer-related mortality worldwide. Growing evidence indicates that metabolic syndrome components, including obesity, insulin resistance, and hyperglycemia, contribute to PCa development, and progression to more aggressive form. At the same time, standard treatments such as androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs) significantly improve oncologic outcomes but are associated with adverse metabolic effects, including increased fat mass, insulin resistance, and sarcopenia, potentially worsening patients’ overall metabolic profile and quality of life. Tumor progression in PCa is strongly driven by androgen receptor (AR) signaling, which is closely linked to cellular metabolic reprogramming, highlighting metabolism as a potential therapeutic target. Aim: The aim of this study was to evaluate and synthesize current evidence on the role of the ketogenic diet (KD) in PCa, with particular emphasis on its interaction with hormonal therapies, underlying metabolic and endocrine mechanisms, and its potential application as an adjunctive strategy in integrated oncologic care. Results: The KD, characterized by high fat and very low carbohydrate intake, induces a metabolic state of ketosis that reduces circulating glucose, insulin, and insulin-like growth factor 1 (IGF-1), potentially counteracting metabolic alterations associated with PCa and its treatments. Preclinical studies consistently demonstrate that carbohydrate restriction and KD can slow tumor growth, modulate key oncogenic pathways such as PI3K/AKT/mTOR, reduce systemic insulin signaling, and enhance survival in prostate cancer models. Additionally, emerging evidence suggests possible synergistic effects when KD is combined with standard therapies, including ADT and immunotherapy. Clinical data, although limited, indicate that low-carbohydrate dietary interventions may improve metabolic parameters and could delay biochemical progression, as suggested by increased prostate-specific antigen (PSA) doubling time. However, results across studies remain heterogeneous, and robust evidence on long-term oncologic outcomes is lacking. Conclusions: Overall, the KD represents a promising but still experimental strategy in PCa management, requiring careful nutritional supervision to avoid adverse effects such as unintended weight loss or sarcopenia. Further well-designed randomized clinical trials are needed to clarify its safety, efficacy, and role in routine clinical practice. Full article

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening vascular disease lacking therapies that target underlying cell death pathways. Ferroptosis, an iron-dependent form of lipid peroxidation-driven cell death, has emerged as a key mechanism in vascular remodeling. We investigated whether exogenous ketosis induced by ketone ester (KE) supplementation can suppress ferroptosis and prevent TAAD. TAAD was induced in C57BL/6 mice using β-aminopropionitrile (BAPN). A subset of these mice received KE [(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, 20 g/L] in their drinking water starting on day 15 of the BAPN treatment. Human aortic smooth muscle cells (HASMCs) were treated with the GPX4 inhibitor Ras-Selective Lethal 3 (RSL3) and β-hydroxybutyrate (β-OHB) to investigate ferroptotic markers, lipid peroxidation, and labile iron levels. KE supplementation significantly reduced TAAD incidence (69% → 43%) and improved survival rate (52% → 73%), while preserving aortic structure and reducing elastic fiber fragmentation. Transcriptomic analyses of human TAAD datasets (GSE153434 and GSE52093) and single-cell RNA sequencing data (GSE155468) revealed ferroptosis signatures characterized by decreased GPX4 and increased expression of iron metabolism genes. Mechanistically, KE suppressed BAPN-induced iron accumulation and lipid peroxidation in vivo. In HASMCs, β-OHB inhibited ferroptosis induced by GPX4 inhibition, decreasing lipid peroxidation and labile iron levels. KE restored GPX4 and SLC7A11 expression while suppressing HO-1 in vivo, with effects dependent on Nrf2 signaling in vitro. In summary, ketone ester supplementation protects against TAAD by inhibiting VSMC ferroptosis via GPX4 induction and HO-1 suppression, highlighting a potential therapeutic strategy for aortic disease. Full article

Background/Objectives: Lung cancer (LC) remains the leading cause of cancer-related death worldwide, despite advances in systemic and targeted therapies. A mechanism of survival of tumor cells is metabolic reprogramming, characterized by increased glucose uptake, aerobic glycolysis, and alterations in mitochondrial function. These adaptations seem to support tumor growth, immune evasion, and therapeutic resistance. In parallel, supportive care and specifically nutritional interventions have become essential components of modern oncology. The interplay between metabolic reprogramming and targeted nutritional strategies represents a promising area of investigation that bridges tumor biology with supportive care, aiming to enhance both therapeutic efficacy and patient quality of life. Methods: This narrative review explores the biological and pathophysiological rationale for the ketogenic diet (KD) as a possible complementary intervention in LC management and summarizes the published preclinical and clinical data supporting this rationale. Results: We discuss key aspects of tumor metabolism, including the Warburg effect, glucose dependency, oxidative stress regulation, fatty acid metabolism, lactate cycling and tumor microenvironment interactions, with particular emphasis on how carbohydrate restriction and ketosis may exacerbate mitochondrial dysfunction in cancer cells and modulate inflammatory pathways. Furthermore, we summarize available preclinical and clinical evidence evaluating the KD in oncology and, more specifically, in LC, focusing on feasibility, safety, metabolic effects, and potential synergy with chemotherapy, radiotherapy, and immunotherapy. Conclusions: While preclinical models suggest enhanced treatment efficacy, clinical data remain limited and heterogeneous, with patient adherence representing a major challenge. Further well-designed longitudinal studies are required to clarify the therapeutic role of the ketogenic diet in lung cancer. Full article

Ketosis is a major metabolic disorder that significantly impacts dairy cow health, welfare, and farm profitability, posing challenges to both farmers and veterinarians. This opinion paper, derived from expert panel discussions and a review of the scientific literature, provides a comprehensive, proactive approach to modern ketosis management. It addresses the critical need for increased farmer awareness, emphasizing the veterinarians’ involvement as consultants and data interpreters and equipping them with essential skills in data analysis, communication, and farmer education. This paper also details a practical toolbox of diagnostic, therapeutic, management, and preventive strategies, including precision technologies and welfare-enhancing practices, to optimize metabolic health, enhance productivity, and ensure the long-term sustainability of dairy farming. This expert consensus translates scientific knowledge into practical on-farm actions, empowering farmers with risk-based insights and equipping veterinarians with tools and strategies for success. Ultimately, the consensus of our opinion paper reflects an industry-wide transition toward absolute transparency in diagnostic reporting, based on reliable data that creates an indispensable foundation for evidence-based ketosis management. Full article

The transition from energy sufficiency to deficiency triggers complex metabolic and immune adaptations that have traditionally been viewed through a reductionist pathological lens. During early lactation, coordinated mobilization of adipose tissue, muscle protein, and bone minerals supports milk synthesis, with ketogenesis specifically arising from hepatic oxidation of non–esterified fatty acids. This review introduces the Keto–Inflammatory Network (KIN), a novel framework positioning ketonemia as an evolutionarily conserved adaptive response rather than inherent metabolic dysfunction. The KIN integrates β–hydroxybutyrate (BHB) signaling with immune modulation, epigenetic regulation, circadian rhythms, and microbiota interactions. Through mechanisms including NLRP3 inflammasome inhibition, HDAC–mediated epigenetic modifications, and HCAR2 receptor activation, ketone bodies orchestrate anti–inflammatory responses while maintaining metabolic flexibility. Building upon important precedent work recognizing beneficial roles of ketones in ruminant metabolism, this review synthesizes recent advances in immunometabolism and systems biology into an integrated framework. The KIN encompasses calcium–ketone integration through the Calci–Keto–Inflammatory Code (CKIC), temporal regulation via the Ketoinflammatory Clock, and trans–kingdom signaling through microbiota interactions. In dairy cattle, this perspective reframes periparturient ketonemia as existing on a continuum from adaptive to pathological, with biological meaning determined by integrated metabolic–inflammatory patterns rather than absolute ketone concentrations. The CKIC paradigm, while requiring prospective validation, suggests novel therapeutic approaches leveraging ketone signaling for inflammatory diseases, autoimmune conditions, and metabolic disorders while challenging traditional threshold–based ketosis management strategies. This systems–level understanding opens new avenues for precision interventions that work with, rather than against, evolved adaptive mechanisms refined through millions of years of mammalian evolution. By distinguishing ketonemia (measurable ketone elevation) from pathological ketosis (dysregulated ketone accumulation), and by integrating evidence from both ruminant and monogastric models, this review provides a comprehensive framework for next–generation metabolic medicine. Full article

Background: Neonatal hypoxic–ischemic encephalopathy remains a leading cause of neonatal mortality and long-term neurodevelopmental disability worldwide. Despite the widespread adoption of therapeutic hypothermia, a substantial proportion of affected infants experience death or significant neurological impairment. Given their metabolic vulnerability, ketogenic diet strategies and ketone bodies have emerged as potential adjunctive neuroprotective interventions. This scoping review aims to critically evaluate the mechanistic rationale, preclinical evidence, and clinical feasibility of ketogenic approaches. Methods: A scoping review of the literature was conducted, including experimental and clinical studies investigating ketogenic diets, endogenous ketosis, and exogenous ketone supplementation in neonatal hypoxia–ischemia. Evidence was synthesized across mechanistic, preclinical, nutritional, and clinical domains, with particular attention to developmental context, timing of intervention, safety considerations, and translational relevance in the contest of therapeutic hypothermia. Results: Preclinical studies consistently demonstrate that ketone bodies enhance cerebral energy metabolism, support mitochondrial function, reduce excitotoxic signaling, and attenuate oxidative stress and neuroinflammation in the immature brain. Neonatal models show preferential utilization of β-hydroxybutyrate over glucose during hypoxic–ischemic stress, suggesting intrinsic metabolic advantages. Emerging evidence also supports potential long-term effects on epigenetic regulation and white matter development, although direct causal validation in neonatal HIE remains limited. Nutritional studies indicate that carefully monitored enteral and parenteral feeding is feasible in critically ill neonates, identifying a potential window for metabolic interventions. Conclusions: Ketogenic strategies represent a plausible, multimodal approach to targeting the metabolic and inflammatory sequelae of neonatal HIE. While current evidence is insufficient to support clinical implementation, this scoping review provides a hypothesis-generating framework to guide future translational research and the design of carefully controlled clinical trials in neonatal neurocritical care. Full article

Bovine ketosis represents a critical metabolic challenge in modern dairy production, primarily affecting high-yielding cows during the periparturient period. The disorder arises from severe negative energy balance (NEB), where energy demands exceed supply, triggering substantial mobilization of adipose tissue and hepatic accumulation of non-esterified fatty acids (NEFAs). This stress overwhelms hepatic oxidative capacity, leading to incomplete fatty acid oxidation and excessive ketone body production—primarily β-hydroxybutyrate (BHB), acetoacetate, and acetone. While genomics enables the identification of candidate genes and genetic variations influencing ketosis susceptibility, metabolomics provides comprehensive, multi-matrix metabolic signatures across blood, milk, urine, and tissues, often revealing predictive biomarkers in the dry period and pre-clinical stage. This review provides a comprehensive overview of ketosis etiology, emphasizing the roles of NEB, fat mobilization, hormonal dysregulation, and oxidative stress. We systematically examine candidate genes, signaling pathways, and the diverse metabolomic profiles underlying disease pathogenesis, and discuss current prevention strategies focusing on periparturient nutritional management and therapeutic interventions. Understanding these integrated molecular and metabolic mechanisms offers valuable insights for developing targeted breeding programs and precision management approaches to enhance metabolic health and economic efficiency in dairy cattle. Full article

Background/Objectives: Ketogenic diets (KDs), defined by very low carbohydrate and high fat content, are widely studied for obesity and metabolic disease. However, KD formulations vary from 60–95% fat, leading to inconsistent induction of ketogenesis and variable outcomes. The fat threshold required for sustained ketosis, and the tissue-specific programs that mediate KD efficacy, remain unclear. Methods: We evaluated multiple KD formulations (80–95% fat) in C57BL/6J wild-type (WT) and diet-induced obese (DIO) mice. Plasma, hepatic, and intestinal β-hydroxybutyrate (BHB) were measured together with expression of ketogenesis and fatty acid oxidation genes. Body weight, adipose distribution, and liver morphology were assessed under both direct feeding and therapeutic settings. Results: In WT mice, only diets exceeding 85% fat induced robust ketogenesis, reflected by elevated BHB and hepatic upregulation of Cd36, Cpt1a, Acat1, and Hmgcs2. Moderate KDs (80–85%) failed to trigger ketosis and resembled high-fat feeding. In obese mice, an 80% KD lowered fasting glucose without reducing body weight, whereas a 90% KD promoted systemic ketosis, weight loss, and adipose reduction. Interestingly, hepatic transcriptional programs for fatty acid oxidation and ketogenesis were suppressed under 90% KD despite elevated BHB, suggesting reliance on substrate availability and peripheral utilization. In contrast, intestinal Hmgcs2 was strongly induced in both WT and DIO mice, with Oxct1 upregulated only in obesity, indicating local ketone production and consumption. Conclusions: These findings identify > 85% dietary fat as a threshold for sustained ketosis and highlight distinct liver–intestine contributions, underscoring ketogenesis as the central driver of KD’s anti-obesity benefits. Full article

Background/Objectives: Ketone bodies are increasingly studied for their potential therapeutic effects, particularly through exogenous ketosis, in a variety of diseases. This systematic review aimed to rigorously assess the clinical efficacy of exogenous ketosis in adults with medical conditions. Methods: Following PRISMA guidelines, we systematically searched MEDLINE and Scopus databases. Our inclusion criteria were defined according to the PICOS framework, focusing on studies involving exogenous ketosis in adult patients with specific diseases. The study is registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42023492846). Results: After a stringent selection process, fifty-one studies were analyzed. Twenty-two studies focused on neurological disorders, one on psychiatric disorders, twenty-two on metabolic disorders, five on cardiovascular disorders, and one on an inflammatory disorder. Exogenous ketosis demonstrated potential benefits across multiple conditions, including Alzheimer’s disease, mild cognitive impairment, McArdle’s disease, various forms of heart failure, cardiogenic shock, pulmonary hypertension, and COVID-19-related acute respiratory distress syndrome, although evidence is mostly limited to surrogate endpoints with insufficient hard outcome data. Subtherapeutic ketone concentrations induced by medium-chain triglycerides and limited follow-up periods often precluded firm conclusions regarding clinically meaningful outcomes. Conclusions: Exogenous ketosis shows potential in neurological, metabolic, and cardiovascular disorders, while evidence in psychiatric and inflammatory conditions remains scarce and preliminary. Ketone esters appear preferable for effective and tolerable ketosis. Future research should focus on identifying responsive patient populations, optimizing treatment regimens, and conducting long-term clinical trials with hard endpoints to validate these findings. Full article

Background: The ketogenic diet (KD), a high-fat and low-carbohydrate dietary approach, has been used therapeutically in drug-resistant epilepsy and other neurological and metabolic disorders. Recent interest has shifted toward understanding its broader metabolic effects through metabolomics. This review aims to summarize current knowledge on the biochemical mechanisms and therapeutic implications of the KD, with a particular focus on metabolomic profiling and neurological health. Methods: This narrative review synthesizes findings from the last five years of metabolomic studies investigating the biochemical consequences of the KD and its variants, including the classical KD, modified Atkins diet (MAD), medium-chain triglyceride diet (MCT), and low glycemic index treatment (LGIT). The review integrates data on analytical techniques, such as liquid chromatography–mass spectrometry (LC-MS) and gas chromatography–mass spectrometry (GC-MS), and evaluates alterations in key metabolic pathways. Results: The KD significantly modulates energy metabolism, shifting adenosine triphosphate (ATP) production from glycolysis to fatty acid oxidation and ketone body utilization. It affects mitochondrial function, one-carbon metabolism, redox balance, neurotransmitter regulation, and gut–brain axis signaling. Metabolomic profiling has identified β-hydroxybutyrate (βHB) as a key regulatory metabolite influencing mitochondrial respiration. Long-term KD use may impact renal and hepatic function, necessitating clinical caution and individualized nutritional monitoring. Conclusions: Metabolomic analysis provides critical insights into the multifaceted effects of the KD, supporting its role as a targeted metabolic therapy in neurological diseases. However, potential risks linked to prolonged ketosis warrant further investigation. Future studies should focus on personalized applications and long-term safety profiles of KD variants across patient populations. Full article

β-hydroxybutyrate (BHB) is the most abundant ketone body produced during ketosis, a process initiated by glucose depletion and the β-oxidation of fatty acids in hepatocytes. Traditionally recognized as an alternative energy substrate during fasting, caloric restriction, and starvation, BHB has gained attention for its diverse signaling roles in various physiological processes. This review explores the emerging therapeutic potential of BHB in the context of sarcopenia, metabolic disorders, and neurodegenerative diseases. BHB influences gene expression, lipid metabolism, and inflammation through its inhibition of Class I Histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs), specifically HCAR2 and FFAR3. These actions lead to enhanced mitochondrial function, reduced oxidative stress, and regulation of inflammatory pathways, with implication for muscle maintenance, neuroprotection, and metabolic regulation. Moreover, BHB’s ability to modulate adipose tissue lipolysis and immune responses highlight its broader potential in managing chronic metabolic conditions and aging. While these findings show BHB as a promising therapeutic agent, further research is required to determine optimal dosing strategies, long-term effects, and its translational potential in clinical settings. Understanding BHB’s mechanisms will facilitate its development as a novel therapeutic strategy for multiple organ systems affected by aging and disease. 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