Search Results (207)

Background and Clinical Significance: Overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) in children is a rare but life-threatening metabolic emergency. The coexistence of hyperosmolality and ketoacidosis increases neurologic vulnerability and complicates fluid and insulin management. Early identification and osmolality-guided therapy are essential to prevent cerebral edema and other complications. This case describes a 5-year-old boy with new-onset type 1 diabetes mellitus (T1D) presenting with DKA/HHS overlap two weeks after influenza vaccination—an unusual temporal association without proven causality. Case Presentation: A previously healthy 5-year-old presented with progressive polyuria, polydipsia, nocturnal enuresis, fatigue, and drowsiness. Two weeks earlier, he had received the influenza vaccine. Examination revealed moderate dehydration without Kussmaul respiration or altered consciousness. Laboratory evaluation showed glucose 45.9 mmol/L (826 mg/dL; reference 3.9–7.8 mmol/L), venous pH 7.29 (reference 7.35–7.45), bicarbonate 12 mmol/L (reference 22–26 mmol/L), moderate ketonuria, and measured serum osmolality 344 mOsm/kg (reference 275–295 mOsm/kg), fulfilling diagnostic criteria for DKA/HHS overlap. After an initial 20 mL/kg 0.9% NaCl bolus, fluids were adjusted to maintenance plus approximately 10% deficit using 0.45–0.75% NaCl according to sodium/osmolality trajectory. Intravenous insulin (approximately 0.03–0.05 IU/kg/h) was initiated once blood glucose no longer decreased adequately with fluids alone and had stabilized near 22.4 mmol/L (≈400 mg/dL). Dextrose was added when glucose reached 13.9 mmol/L (250 mg/dL) to avoid rapid osmolar shifts. Hourly neurological and biochemical monitoring ensured a glucose decline of 2.8–4.2 mmol/L/h (50–75 mg/dL/h) and osmolality decrease ≤3 mOsm/kg/h. The patient recovered fully without cerebral edema or neurologic sequelae. IA-2 antibody positivity with low C-peptide and markedly elevated HbA1c confirmed new-onset T1D. Conclusions: This case highlights the diagnostic and therapeutic challenges of pediatric DKA/HHS overlap. Osmolality-based management, conservative insulin initiation, and vigilant monitoring are crucial for preventing complications. The temporal proximity to influenza vaccination remains incidental. Full article

Background: Acute necrotizing esophagitis (ANE), also known as “black esophagus,” is a rare but life-threatening condition typically occurring in critically ill patients with profound systemic disturbances. Extreme hyperglycemic crises represent an underrecognized precipitating factor, capable of inducing severe metabolic, inflammatory, and microvascular injury. Case Presentation: We report the case of a 54-year-old male admitted with altered mental status and severe dehydration, in whom initial laboratory evaluation revealed extreme hyperglycemia (serum glucose ~1000 mg/dL), metabolic acidosis, and early multiorgan dysfunction. During intensive care unit hospitalization, the patient developed anemia and severe thrombocytopenia, followed by evidence of upper gastrointestinal bleeding. Urgent upper gastrointestinal endoscopy demonstrated diffuse circumferential black necrosis of the distal esophageal mucosa with abrupt demarcation at the gastroesophageal junction, consistent with acute necrotizing esophagitis, along with associated erosive hemorrhagic gastritis. Comprehensive laboratory evaluation documented marked inflammatory activation and hematologic instability. Management and Outcome: Treatment consisted of aggressive metabolic correction, strict glycemic control, hemodynamic stabilization, infection management, and supportive gastrointestinal care. Progressive clinical and biological improvement was observed, with resolution of bleeding and partial recovery of hematologic parameters. Conclusions: This case highlights a severe hyperglycemic crisis as a major contributing factor within a multifactorial ischemic and inflammatory cascade leading to acute necrotizing esophagitis. Full article

Objectives: to assess the safety profile of Gastrointestinal (GIT), renal, and pancreatic effects of GLP-1 and dual receptor agonists. Methods: Disproportionality analyses were performed on FDA Adverse Event Reporting System (FAERS) data following each drug’s approval for weight management. Signals were identified using Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) with 95% confidence intervals (CIs). Results: Among GIT AEs, semaglutide (n = 12,321; 1.65%) showed the strongest signals (PRR 3.97, ROR 14.21), exceeding liraglutide (n = 5972, 0.45%, PRR 2.76, ROR 5.01) and tirzepatide (n = 4056, 3.48%, PRR 1.64, ROR 1.90). For renal and pancreatic outcomes, liraglutide demonstrated the highest overall signal (PRR 4.91, ROR 5.35), particularly for acute pancreatitis (PRR 18.9, ROR 19.4) and pancreatic carcinoma (PRR 18.6, ROR 19.5). Semaglutide showed stronger associations with diabetic ketoacidosis (DKA) (PRR 5.86, ROR 5.9) and acute kidney injury (AKI) (PRR 1.25, ROR 1.25). Tirzepatide demonstrated weaker or absent signals across most outcomes. Conclusions: This study revealed that semaglutide was most associated with GIT events, while liraglutide showed stronger renal and pancreatic signals. Novel associations with DKA and AKI were observed, warranting clinical vigilance. Findings should be cautiously interpreted given surveillance limitations, emphasising the need for large-scale real-world studies to confirm safety profiles. Full article

Timely recognition of type 1 diabetes (T1D) in children and adolescents is crucial to prevent acute complications such as diabetic ketoacidosis (DKA). This narrative review examines the pathophysiology, clinical presentation, and diagnostic challenges of childhood T1D, including the young age of onset, clinician training gaps, and overlapping symptomatology between T1D and other common pediatric illnesses. Despite increased awareness, a significant proportion of children still present with DKA at diagnosis due to misinterpretation of symptoms, such as polydipsia, polyuria, and weight loss. This work emphasizes the importance of early recognition, timely intervention, and the use of structured management algorithms for primary care clinicians. Strategies to reduce DKA incidence, based on existing literature, successful real-world examples, and current guidelines, include enhanced screening for high-risk populations, educational initiatives, and improved diagnostic protocols. By implementing systematic approaches and public health campaigns, healthcare providers can improve early T1D detection and prevent severe DKA complications, ultimately enhancing patient outcomes and reducing long-term morbidity. Full article

Background: SGLT2 inhibitors are key therapies in heart failure (HF), but their combined multidomain effects have not been analyzed together. Methods: We conducted a PROSPERO-registered (CRD420251235850) systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing SGLT2i (dapagliflozin, empagliflozin, canagliflozin, sotagliflozin) with placebo in adults with HF, regardless of ejection fraction or diabetes status. We searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Web of Science through 1 February 2025. Outcomes were grouped into four domains: (1) clinical events, (2) symptoms/health status (Kansas City Cardiomyopathy Questionnaire, KCCQ), (3) functional capacity (6 min walk distance, peak VO₂), and (4) cardiac remodeling/energetics (cardiac MRI, 31P-MRS). We used random-effects models with Hartung–Knapp adjustment and assessed heterogeneity by I² and prediction intervals. Results: Eleven RCTs with 23,812 patients (HFrEF, HFmrEF, HFpEF, and acute or recently decompensated HF) were included. SGLT2i lowered the risk of cardiovascular death or first HF hospitalization by 23% (HR 0.77, 95% CI 0.72–0.82; p < 0.0001; I² = 28%; prediction interval 0.68–0.87), with similar effects across ejection fraction, diabetes status, and presentation type. All-cause and cardiovascular mortality dropped by 12% (HR 0.88, 95% CI 0.81–0.96) and 14% (HR 0.86, 95% CI 0.78–0.95), respectively. SGLT2i improved KCCQ—Clinical Summary Score by 4.6 points (95% CI 3.4–5.8; p < 0.0001) and increased the odds of a ≥5-point improvement (OR 1.49, 95% CI 1.32–1.68; NNT = 12). Six-minute walk distance increased by 21.8 m (95% CI 9.4–34.2; p = 0.001), and mechanistic trials showed significant reverse remodeling (ΔLVEDV −19.8 mL, ΔLVEF +6.1%; both p < 0.001). No improvement was observed in myocardial PCr/ATP ratio. Safety was favorable, with no excess ketoacidosis or severe hypoglycemia. Conclusions: This multidomain synthesis demonstrates that SGLT2 inhibitors provide consistent, robust reductions in mortality and hospitalizations, while also delivering early, clinically meaningful improvements across multiple patient-centered domains. These results establish SGLT2i as a foundational component of contemporary HF management. Full article

Background: Children can be removed from their home if allegations of abuse or neglect are substantiated. The preference is to place them with family members. In the most extreme cases, a child may be placed in a congregate care setting. A child with diabetes should only be placed in such a facility if the staff have been appropriately trained. Otherwise, the consequences can be devastating. In 2022 and 2024, two children were placed into congregate care facilities in Arizona and died of diabetic ketoacidosis due to a lack of appropriate employee training. Study Objective: We aim to inform providers of the legal processes and laws that can result in a child being placed into a congregate care setting. We analyze what went wrong in the care of these two children. We present alternative pathways that might ensure the safety of children before they are placed in such facilities. Methodology: We reviewed public information for cases of morbidity and mortality in children with diabetes in congregate care. We reviewed the California Welfare and Institution legal codes and applicable laws in the Federal Register. We obtained information regarding children with diabetes mellitus who were in the care of child welfare on PubMed. Results and Conclusions: While there are legal safeguards for children with diabetes who are placed in congregate care, these safeguards are ineffective if staff are inappropriately trained. We present programs and recommendations to prevent a child who is placed in a congregate care facility from suffering medical complications or death. Full article

Objectives: Children may present with acute kidney injury (AKI) and polyuria under certain conditions which can complicate diagnosis and management. This review seeks to synthesize AKI presentations in children with polyuria. Methods: Publications for this systematic review were searched using Embase, PubMed, and Scopus. Methodological quality assessment of the included study and case reports was performed. Results: From the selected studies, we obtained data on 32 patients with a mean age of 11.02 ± 2.82 years, including 13 males and 19 females. Among them, 26 presented with polyuria: 19 with diabetic ketoacidosis (DKA), 5 with new-onset type 1 diabetes mellitus (T1DM) without DKA, 1 with Bartter syndrome, and 1 with neuroblastoma. In 12 patients with DKA, data to calculate AKI prevalence were not available. Among the remaining 20 patients (all with polyuria), 9 (45%) developed AKI. AKI stage 3 was observed in 4 patients and stage 2 in 1 patient. For the remaining 5 patients with AKI, no information about the AKI stage was available. Conclusions: AKI can present with polyuria as part of its pathophysiological mechanism. A relationship between polyuria and AKI (with KDIGO stage ≥ 2) was found in metabolic disorders (DKA), nephrological diseases (Bartter syndrome), and oncological conditions (neuroblastoma). Full article

Background: At the onset of Type 1 Diabetes (T1D), international guidelines recommend initiating subcutaneous insulin therapy within a wide dosage range (0.5–1 IU/kg/day), as insulin requirement (IR) varies greatly based on several factors, including age, pubertal status, and the presence of diabetic ketoacidosis (DKA). In clinical practice, some individuals require higher-than-expected IR, leading to prolonged hospitalization. This study aimed to identify predictive factors for elevated IR at T1D onset. Methods: We conducted a retrospective observational study including 218 children and adolescents diagnosed with T1D between January 2010 and September 2020. Clinical and laboratory parameters were collected. IR was defined as the highest daily subcutaneous insulin dose (IU/kg/day) during hospitalization, after resolution of DKA. Results: As expected, DKA severity and HbA1c levels were associated with increased IR. However, the strongest independent predictor in the multivariate model was serum triglyceride level (β = 0.27, p < 0.001), with an adjusted R² of 0.37. No evidence of multicollinearity was detected, and ROC analysis yielded an AUC of approximately 0.70. Conclusions: Hypertriglyceridemia at T1D onset is independently associated with higher IR, regardless of DKA severity. Early recognition of this marker could help optimize insulin dosing, improve metabolic stabilization, and potentially shorten hospital stays. Full article

Companion animal endocrinology has benefited from international standardisation of disease terminology for diabetes mellitus, Cushing’s syndrome, and hypoadrenocorticism through Project Agreeing Language in Veterinary Endocrinology (ALIVE). A group of 14 experts and one chair convened for the third cycle of Project ALIVE, focusing on thyroid disease terminology. The cycle employed the modified Delphi approach from previous cycles, augmented by procedural refinements—such as inclusion of an off-site chair and stricter adherence to timelines —to improve efficiency and flexibility. Novel in this round was the integration of feedback from a previous cycle, which resulted in updated definitions for diabetes mellitus originally developed in ALIVE Cycle 1. Outcomes: A 100% consensus was achieved among panellists and 91.4–100% among 105 members of international veterinary endocrinology societies (32% of total memberships) over 78 thyroid-related terminology items and five revised definitions pertaining to diabetes mellitus. These standardised definitions are expected to facilitate clearer communication and education, enhance diagnostic consistency, support research comparability, and improve clinical care in feline and canine endocrine diseases. Full article

Background/Objectives: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are widely used in type 2 diabetes mellitus for glycemic control and cardiovascular–renal protection, but adverse effects such as acute kidney injury (AKI), urinary tract infection (UTI), euglycemic diabetic ketoacidosis (Eu-DKA), and acute pancreatitis remain concerns. We aimed to determine the prevalence of adverse drug reactions (ADRs) associated with SGLT2 inhibitor use. Methods: This retrospective study assessed the prevalence of these adverse events and identified factors associated with UTI among SGLT2 inhibitor users at Suddhavej Hospital (1 January 2019–15 August 2023). Data were extracted from the hospital electronic medical record system (BMS-HOSxP). Results: We analyzed 293 patients (59.73% male; mean age 63.08 ± 0.667 years; 62.08% aged >60). Dapagliflozin had the highest prevalence of AKI (11.42%) and UTI (13.40%). No acute pancreatitis cases were reported. Logistic regression identified female sex (odds ratios [OR] 2.31, 95% confidence intervals [CI] 1.08–4.96; p = 0.032), AKI diagnosis (OR 3.31, 95% CI 1.10–9.89; p = 0.032), age ≥ 60 years (OR 2.78, 95% CI 1.09–7.09; p = 0.033), and SGLT2 inhibitor use <6 months (OR 5.78, 95% CI 2.74–14.18; p = 0.017) as significant risk factors for UTI. Conclusions: Dapagliflozin was associated with the highest prevalence of AKI and UTIs. Female sex, AKI diagnosis, age ≥ 60 years, and SGLT2 inhibitor use <6 months were significant risk factors for UTI among SGLT2 inhibitor users. Full article

Background/Objectives: Type 1 diabetes (T1D) is a common childhood condition with rising global incidence. Because early-onset T1D coincides with key periods of brain maturation, affected children may face neurocognitive risks. This review summarizes current evidence on the neurocognitive impact of pediatric T1D and related clinical implications. Methods: A structured search of PubMed, Scopus, and Web of Science (inception–October 2025) used combinations of terms related to T1D, cognitive outcomes, and brain imaging. Studies involving participants under 18 years that reported cognitive or neuroimaging findings were included. Results: Diabetic ketoacidosis (DKA) at diagnosis is consistently linked with acute and longer-term neurological injury, including reduced brain volume and potential persistent deficits in memory and executive functioning. Severe or recurrent hypoglycemia disproportionately affects the hippocampus, contributing to lasting learning and memory impairments. Chronic hyperglycemia is a major driver of progressive neurocognitive decline; higher HbA1c is associated with smaller brain volumes and poorer executive function, attention, and processing speed. Early-onset disease and longer duration further increase vulnerability. These neurocognitive effects translate into modest reductions in academic performance and quality of life, especially with poor glycemic control. Emerging evidence suggests that continuous glucose monitoring, insulin pumps, and hybrid closed-loop systems improve metabolic stability and may support healthier brain development. Conclusions: T1D children experience subtle but meaningful neurocognitive risks shaped by glycemic extremes and early disease onset. Routine neuropsychological monitoring, strengthened academic support, and wider use of advanced diabetes technologies may help preserve cognitive development. Larger, longitudinal neuroimaging studies are needed to guide targeted neuroprotective strategies. Full article

Diabetes mellitus (DM) is a complex, heterogeneous, hyperglycemic chronic metabolic disorder. Type 2 diabetes mellitus (T2DM) is characterized by progressive loss of insulin secretion from pancreatic islet β-cells due to IR (insulin resistance), which is a feature of metabolic syndrome (MetS). Chronic hyperglycemia in patients with T2DM in synergy with other metabolic abnormalities causes complications such as diabetic ketoacidosis, osmotic diuresis and hyperglycemic diabetic coma, as well as chronic microvascular and macrovascular complications such as atherosclerotic cardiovascular disease (ASCVD), peripheral artery disease (PAD) and cerebrovascular events, which implicate the formation of reactive species and the promotion of inflammatory pathways. In these events, natural or synthetic antioxidants and minerals seem to have ameliorative effects and may serve as beneficial co-treatment options. In view of these terms, the aim of this study is to investigate the underlying mechanisms of T2DM, its clinical presentation, and its complications. Additionally, the association of the pathogenesis of T2DM and the occurrence of its complications with obesity, chronic inflammation, oxidative stress (OS), insulin resistance (IR), hepatic steatosis, and dyslipidemia is examined, whilst molecular pathways, such as NF-κB and JAK/STAT, are also summarized, under the scope of the effects of several antioxidant compounds and minerals on their progression. The interrelation of T2DM with these conditions, as well as the effects of antioxidant supplementation, seems to be bidirectional, and it is recommended that obese patients be screened for T2DM and adopt lifestyle changes, including exercise, diet modification, and weight loss, in addition to potentially taking multifunctional supplements that offer antioxidant and anti-inflammatory potential. However, many aspects of the protective mechanisms of such antioxidants remain to be elucidated, with more drawbacks in their pharmacokinetic behavior, such as their poor absorption and solubility, waiting to be resolved. Full article

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have become key therapeutic agents based on their protective cardiovascular and renal effects. However, their safety and efficacy in patients with kidney failure, especially undergoing peritoneal dialysis (PD), who are a population at very high cardiovascular risk, remain largely unexplored. Methods: We conducted a retrospective global cohort study using the electronic health records of 19,871 adult peritoneal dialysis patients from the Global Collaborative Network TriNetX database. Of these, n = 412 patients used SGLT2is within 3 months after PD initiation. After propensity score matching, n = 367 patients per cohort were evaluated for cardiovascular risk, mortality and adverse events related to SGLT2is-treatment. Results: The mean age of PD patients with SGLT2is use was 58.7 years and common comorbidities were heart failure (74.0%) and type 2 diabetes (62.1%). Comedication included beta blocking agents (75.5%), diuretics (74.0%), statins (64.6%), insulins (60.2%) and renin- angiotensin blockade (56.3%) in the majority of patients. After propensity score matching, SGLT2is use showed a trend towards reduced all-cause mortality or major adverse cardiovascular events but no significant risk reduction. Further, incidence of hemodialysis was not lowered by SGLT2is use. Known adverse events of SGLT2is use such as ketoacidosis, genitourinary infections, dehydration or peritonitis were not increased among users. Conclusions: In this cohort of PD patients with high cardiovascular and metabolic risk factors, SGLT2is use was safe with regard to unchanged adverse events, while effects on mortality, cardiovascular outcomes, and technique failure were neutral. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by reactivating T cell-mediated anti-tumor immunity. However, this enhanced immune activity can lead to immune-related adverse events (irAEs). This narrative review focuses on endocrine irAEs, including thyroid dysfunction, hypophysitis, adrenal insufficiency, and diabetes mellitus. It also explores infectious complications and their underlying mechanisms. These mechanisms include immune dysregulation resulting directly from ICI-induced T-cell activation and indirectly from the immunosuppressive therapies used to treat irAEs. Furthermore, potential role of endocrine irAEs in predisposing patients to infectious complications is analyzed. The objective is to provide non-oncology specialists with the clinical insight necessary to recognize and manage these complex side effects. This narrative review synthesizes current literature on the diagnosis, management, and pathophysiology of endocrine irAEs and infections associated with different classes of ICIs (anti-CTLA-4, anti-PD-1, and anti-PD-L1). Endocrine irAEs are common, with incidence varying by ICI type; combination therapies pose the highest risk. Thyroid dysfunction is the most frequent, followed by hypophysitis, which often leads to permanent secondary adrenal insufficiency. ICI-induced diabetes mellitus is a rare but serious complication, frequently presenting as diabetic ketoacidosis. ICIs are believed to induce a distinct array of infections resulting from immunological dysregulation, unrelated to immunosuppressive medication. The phenomenon is increasingly called ICI therapy-induced dysregulated immunity. Moreover, evidence suggests that endocrine irAEs can compromise immune function and lead to a significantly higher risk of bacterial and fungal infections. Identifying infections that imitate irAEs is particularly important because the therapy is significantly distinct. Greater interdisciplinary awareness is crucial for the early recognition and appropriate management of both the endocrine and infectious complications, ultimately improving the safety and outcomes for patients receiving immunotherapy. Full article

Background: Diabetic ketoacidosis (DKA) is a serious acute complication of diabetes mellitus (DM) associated with significant morbidity, mortality, and healthcare burden worldwide. This study aimed to investigate population descriptors and clinical outcomes among adult and pediatric patients admitted with DKA at two tertiary medical centers in Riyadh, Saudi Arabia. Methods: We conducted a retrospective observational study that included adult and pediatric (≤15 years) patients admitted to emergency departments (EDs) and received care for DKA between 2018 and 2021. DKA severity was defined according to the American Diabetes Association (ADA) criteria, which rely on arterial/venous pH and serum bicarbonate (with anion gap supportive), as follows: mild (pH 7.25–7.30; HCO₃⁻ 15–18 mmol/L), moderate (pH 7.00–7.24; HCO₃⁻ 10–15 mmol/L), and severe (pH < 7.00; HCO₃⁻ < 10 mmol/L). Data were extracted from electronic medical records and analyzed descriptively. Results: A total of 373 patients were admitted to the EDs and received treatment for DKA throughout the study period. Adults constituted 71.6% (267/373), while children represented 28.4% (106/373) of the patients; the majority of adults (74.2%) had Type 1 DM (T1DM), while all pediatric patients had T1DM. More than half of the adult presentations met the criteria for severe DKA (55.8%; 149/267), whereas pediatric cases were most commonly moderate in severity (41.5%; 44/106). The most common precipitating factors across both age groups of patients with diabetes before the index DKA event were non-compliance with therapy and infection. Both groups demonstrated typical biochemical features of DKA, although pediatric patients presented with slightly lower bicarbonate and higher anion gaps (slightly greater metabolic acidosis) but with similar hydration status. Regarding patients’ outcomes, hyperkalemia was identified in 23.6% of adults and 24.5% of pediatric patients, while hypokalemia was documented in 20.2% of adults and 24.5% of pediatric patients, and adult patients experienced more acute kidney injuries than the other cohort (5.2% vs. 1.9%). In-hospital mortality was 0.8% (3/373) among all adults. Although pediatric patients experienced faster DKA resolution (median = 16.5 h; IQR, 11.7–25.8) compared to adult patients (23.7 h; 16.2–36.9), they had a longer hospital stay compared to adult patients, and a significant majority required ICU care (50.9%) at some point during their care. Conclusions: The increasing prevalence of DM in Saudi Arabia, especially among the youth, would lead to an increase in DKA burden unless effective preventive measures are taken. This study demonstrated that preventable causes, such as non-compliance with therapy and infection, were responsible for the high admission rates. Thus, comprehensive outpatient care can help strengthen care continuity and help decrease the burden on emergency and inpatient services. Full article