Identifying individuals at risk of early onset type 1 diabetes (diagnosed <2 years) would be highly beneficial in reducing risk of severe diabetic ketoacidosis (DKA) for those with extreme autoimmunity. We aimed to investigate whether genetic variation contributes to heterogeneity in age of type 1 diabetes onset, focusing on those diagnosed <2 years and ages previously defined by histological differences. We carried out association testing on 6773 individuals with type 1 diabetes and tested for heterogeneity in Human Leukocyte Antigen (HLA) variants across stratified age groups (594 diagnosed <2 years, 2241 diagnosed 2-7 years, 3094 diagnosed 7-13 years, 844 diagnosed 13+ years). We used a 67 SNP type 1 diabetes genetic risk score (T1D-GRS) to quantify aggregated genetic risk and assessed its utility in screening for type 1 diabetes <2 years. We observed higher T1D-GRSs as age of onset decreased in type 1 diabetes and found that DR3-DQ2 homozygosity was most strongly associated with <2 years onset (log-OR=4.27). The T1D-GRS showed high discriminative ability for <2 years onset type 1 diabetes onset (AUC=0.94) and correctly identified 88% of type 1 diabetes cases at the 85th population centile. We have shown higher genetic risk for very early onset T1D and suggest T1D-GRSs in newborn screening is likely to be particularly sensitive to those with younger type 1 diabetes onset.

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.

Diabetic ketoacidosis (DKA) is a life-threatening endocrine emergency characterized by metabolic acidosis, hyperglycemia, and ketonemia. Although pH and bicarbonate (HCO₃⁻) levels are commonly used to classify the severity of diabetic ketoacidosis (DKA), base excess (BE) is not included in the current classification. BE is defined as the amount of acid or base required to restore blood pH to normal under standardized conditions. This study evaluated the relationship between BE and DKA severity in patients presenting to the emergency department (ED).This retrospective observational study included adult patients (≥ 18years) diagnosed with DKA in a tertiary ED between January 2022 and December 2024. Data on venous blood gas parameters-pH, HCO₃⁻, lactate, BE, and anion gap-were collected at 0, 4, 12, and 24h. Patients were stratified into mild, moderate, or severe DKA based on American Diabetes Association criteria, which consider factors such as arterial pH, serum HCO₃⁻ level, and mental status, to determine the severity of the condition. 44 patients (mean age 49.72 ± 19.11years; 59.1% male) were analyzed. At admission, BE values were significantly more negative in the severe DKA group (p < 0.001), correlating with lower pH and HCO₃⁻ levels. Across all time points, BE demonstrated significant differences by severity and showed progressive normalization, with delayed recovery in cases of severe disease. A BE cutoff of -14.2 identified moderate/severe DKA with 73.1% sensitivity and 94.4% specificity (AUC: 0.858; 95% CI: 0.720-0.945). BE, a sensitive marker for metabolic acidosis, correlates strongly with DKA severity. The routine use of BE, similar to HCO₃⁻, may support improved clinical management of DKA in emergency settings.

ObjectiveRegular insulin infusion and intravenous fluids are the cornerstones of managing diabetic ketoacidosis (DKA). To shorten the time taken to resolve DKA in known diabetic patients, the concomitant administration of glargine with regular insulin infusion has been tried, with promising results. This study primarily aimed to assess whether the addition of Neutral Protamine Hagedorn (NPH) insulin to continuous insulin infusion (CII) hastens the resolution of DKA. The secondary objectives were to compare the time to rebound hyperglycemia, frequency of hypoglycemia and duration of hospital stay between the early NPH insulin and control groups.ResultsAn open-label, randomised controlled trial (CTRI ref/2022/08/044760, dated August 8, 2022) of 50 adult participants with DKA was conducted from August 2022 to June 2023. In the intervention arm, 25 participants received 0.25 IU/kg subcutaneous NPH insulin in 2 divided doses, along with a continuous insulin infusion from the time of randomization until the primary outcome was achieved. The control arm (n = 25) received the standard of care. The time to resolution of DKA was significantly shorter in the intervention arm [Intervention (I): 20 (16–32) hours vs. Standard (S): 38.5 (27–48) hours] in those with severe DKA (p = 0.01). Rebound hyperglycemia was delayed in the intervention arm [I: 7.9 ± 2.7 h vs. S: 5.9 ± 2.2 h]. There was no significant difference in the duration of hospital stay or frequency of hypoglycemia. However, the small sample size restricts the generalizability of the results and, larger studies are needed for confirmation of these findings.Trial registration: This trial was prospectively registered in the Clinical Trials Registry India (CTRI)-CTRI/2022/08/044760 on August 8, 2022.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13104-025-07508-5.

To evaluate the effectiveness and safety of a hybrid closed-loop (HCL) insulin infusion system in treating adult and adolescent patients with type 1 diabetes (T1D). A total of 126 participants (22 adolescents and 104 adults) underwent a 2-week initial treatment phase followed by a 2-week run-in phase with the Equil® S HCL insulin pump system MTM-Z in Manual Mode with calibration-free continuous glucose monitoring (CGM) System G7, followed by a 12-week study phase with HCL Auto Mode enabled. The primary outcome was the overall mean change in CGM time in range (TIR; 70-180 mg/dL). Safety endpoints included rates of severe hypoglycaemia, hyperglycaemia and diabetic ketoacidosis (DKA). Compared with the baseline run-in, Auto Mode increased TIR from 69.11% to 76.72% (p < 0.001) and reduced time below range (<70 mg/dL) from 3.92% to 2.73% (p < 0.001). The mean sensor glucose (SG) decreased from 151 ± 28 to 144 ± 19 mg/dL. The proportion of achieving TIR of >70% increased from 56.03% to 77.59%. The standard deviation (SD: -5.90 mg/dL) and coefficient of variation (CV: -2.49%) reduced significantly. The greatest change in TIR (mean 20.55%), mean SG (estimated treatment difference [ETD]: -30.13, 95% confidence interval [CI]: -41.84, -18.41; p = 0.001) and SD of SG (ETD: -14.21, 95% CI: -21.17, -6.71; p = 0.004) was observed in participants with a baseline glycosylated haemoglobin A1c (HbA1c) value of >8.0%. The percentage of achieving combined recommendations for time at SG ranges increased from 25.86% to 56.90%. No severe hypoglycaemia, DKA or adverse events were observed. HCL therapy is safe in Chinese adolescent and adult patients with T1D. The 12-week application of the Equil® S HCL insulin pump system MTM-Z with Auto Mode increased TIR and reduced HbA1c, hyperglycaemia and hypoglycaemia.

Abstract Background Diabetic ketoacidosis (DKA) is one of the main causes of end-stage kidney disease (ESKD). Renal resistivity index is a well-known indicator of renal tubulopathy. Objectives To determine the renal resistivity index by duplex ultrasound in children and adolescents with type 1 diabetes mellitus (T1DM) during DKA. Patients and Methods A prospective longitudinal study was conducted over 1 year, where we have included children aged between 6-18 years with T1DM presented to Emergency Room (ER) &amp;Pediatric and Adolescents Diabetes Unit Children Hospital, Faculty of Medicine, Ain Shams University, with moderate and severe DKA and complete clinical and laboratory data about renal function prior to the study was done, we have excluded from our study children with comorbid disorders affecting renal function or any chronic kidney disorders, and renal resistivity index was assessed by using duplex ultra sound scanning. Results During the study period, a total of 40 pediatric patients were included with T1DM with, with a female predominance (90%).The mean (±SD) age at presentation was 10.59±2.17 years.According to eGFR, children with T1DM presented with moderate and severe DKA at presentation were classified as those with proteinuria (18 patients)45% and those without protienuria (22 patients)55% (p &amp;lt; 0.001) .Furthermore children with protienuria had a significantly elevated renal resistivity index of the right kidney with mean (0.64±0.09) and that of the left kidney was (0.57±0.05), with P-value (p &amp;lt; 0.05). Conclusion The renal resistivity index is a good indicator of renal tubulopathy in children and adolescent with DKA at the time of presentation.

Abstract Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus, characterized by hyperglycemia, ketosis, and metabolic acidosis. Severe dehydration and hypovolemic shock in severe DKA are common, but myocardial dysfunction and lactic acidosis are rare. We report a case of an adolescent female who presented with severe DKA in refractory shock, requiring vasoactive support and mechanical ventilation. Myocardial dysfunction and persistent lactic acidosis led to the suspicion of thiamine deficiency. There was a remarkable recovery after administration of intravenous thiamine. This case highlights the importance of suspecting thiamine deficiency-related myocardial dysfunction and lactic acidosis in children with DKA not responding to usual therapy.

Severe diabetic ketoacidosis (DKA) is a critical medical condition that often necessitates emergency treatment and hospitalization. Although DKA primarily impacts individuals with type 1 diabetes (T1D), its annual incidence among adults with T1D ranges from 4% to 8% following diagnosis. Continuous glucose monitoring (CGM) has become a standard tool for managing T1D and type 2 diabetes (T2D) in patients using insulin or aiming to improve self-management. However, advances in continuous dual glucose-ketone monitoring (DGK) technology offer new possibilities for clinical research and patient care. This article explores the potential applications of DGK in clinical research, with a focus on T1D, while also considering its broader relevance for T2D and other patient populations.

Diabetic ketoacidosis (DKA) is a life-threatening diabetes emergency associated with mortality and severe morbidities in individuals with diabetes. DKA mainly presents with significant hyperglycemia (>250 mg/dL); however, with the increasing use of sodium-glucose transporter 2 inhibitors, we are seeing an increase in euglycemic DKA (euDKA) in both type 1 diabetes and type 2 diabetes. Although severe DKA generally requires emergency department services or inpatient hospitalization, clinicians can play an important role in helping patients prevent DKA by providing comprehensive education to their patients regarding early identification of elevated ketone states and intervention for improvement in ketone production, thus potentially preventing the severity of DKA. Although ketone monitoring is recommended for all patients at risk for developing DKA or euDKA, current ketone monitoring methods have significant limitations. Abbott Diabetes Care (Alameda, CA) is developing a dual monitoring system that continuously measures interstitial glucose and β-hydroxybutyrate using a single sensor. This article discusses how continuous dual glucose-ketone monitoring can be integrated into primary care practice when it becomes available.

Diabetic ketoacidosis (DKA) is the most common acute complication and leading cause of mortality in children and adolescents with diabetes. While DKA is mainly seen in type 1 diabetes, youth with type 2 diabetes, especially adolescents, are also susceptible to this condition. As a standard of care, individuals at risk for DKA and their caregivers are provided with instructions for preventing and managing ketone development. However, the use of urine ketone or blood ketone monitoring is often suboptimal. Abbott Diabetes Care (Alameda, CA) is developing a dual monitoring system that continuously measures interstitial glucose and β-hydroxybutyrate using a single continuous dual glucose-ketone (DGK) sensor. The use of continuous ketone monitors in the pediatric population has the potential to improve at-home monitoring and early initiation of intervention with rising ketone levels prior to severe DKA requiring hospitalization. This article reviews the importance of ketone testing, examines current testing options, and discusses how DGK, a novel testing technology, can reduce the occurrence of DKA in children and adolescents who are living with diabetes.

Symptomatic hypophosphatemia in a teenage girl with severe diabetic ketoacidosis

Disclosure: A. Gonell: None. E. Jalal: None. S.R. Saul: None. P.D. Greenberg: None.Introduction: Despite awareness of second-generation antipsychotics' (SGAs) metabolic side effects, diabetic ketoacidosis (DKA) linked to ziprasidone is rare. This case highlights potential DKA risk with long-term ziprasidone use and underscores the need for regular diabetes monitoring. Case: A 58-year-old male with a history of hypertension, cerebrovascular accident, and schizophrenia managed with long-term ziprasidone presented with progressive altered mental status, polydipsia, polyuria, and weight loss over several months. He was lethargic, weak, and had nausea/vomiting. Labs revealed glucose 1418 mg/dL, pH 7.11 (n = 7.35 - 7.45), anion gap 45.4 mEq/L (n = 4 - 12 mEq/L), and +serum acetone, consistent with severe DKA. HbA1c was >15.5% (n < 5.7%, 6.2% one year prior). He was admitted to the Intensive Care Unit and treated per DKA protocol with an insulin drip, hydration, electrolyte repletion, transitioned to a basal-bolus insulin regimen, and saw a full recovery. Islet cell (ICA), zinc transporter (ZnT8), glutamic acid decarboxylase (GAD-65), and insulin antibodies (IAA) were negative. Two months later, C-Peptide was 4.1 ng/mL (n = 0.5 - 2 ng/mL). Review of medications revealed over 10 years of intermittent ziprasidone use. His psychiatrist confirmed ziprasidone was prescribed but taken as-needed for auditory hallucinations without regular refills. The patient’s partner was not aware of recent use. Conclusion: SGAs are linked to weight gain, glucose intolerance, dyslipidemia, and hypertension, most commonly associated with olanzapine and clozapine (Pillinger et al., 2020; Guenette et al., 2013). Proposed long-term mechanisms for development of DKA include metabolism dysregulation, insulin signaling impairment, intrinsic pancreatic β-cell dysfunction, immune modulation, and increased counter-regulatory hormones (Bae et al., 2024). Ziprasidone’s receptor antagonism of 5-HT2A, 5-HT1D, D2, and agonism of 5-HT1a may contribute to development of metabolic syndrome (Goodnick, 2001). In the absence of metabolic syndrome, SGAs may still induce acute hyperglycemia, especially within 6 months of initiation (Bae et al., 2024). Animal studies suggest olanzapine induces PERK-mediated β-cell apoptosis (Ozasa et al., 2013). Our case suggests a possible dose/time-dependent relationship between ziprasidone and DKA. A previous case documented DKA after >10 years of ziprasidone use with profound hyperglycemia at 1114 mg/dL, similar to our patient (Thanikonda et al., 2020). Alternatively, our patient’s intermittent use of ziprasidone may have served as an acute trigger for his presentation. The life-threatening nature of DKA necessitates regular glycemic monitoring and control. Most SGA-associated DKA cases occur shortly after initiation, but ziprasidone-associated DKA long after initiation underscores the need for both early and long-term monitoring.Presentation: Monday, July 14, 2025

Disclosure: K. Conway: None. R. Reguram: None. T. Vora: None. W. Taha: None.Introduction: Chronic pancreatitis is a progressive inflammatory condition resulting in irreversible fibrosis and parenchymal loss. A known complication is secondary diabetes mellitus, termed type 3c diabetes, that typically develops gradually with mild hyperglycemia. It is uncommon for patients with chronic pancreatitis to initially present with severe hyperglycemia and diabetic ketoacidosis (DKA), a hallmark of type 1 diabetes. We present a rare case of a patient with chronic pancreatitis whose first manifestation of diabetes was DKA. Case Presentation: A 42-year-old male with alcohol use disorder, chronic pancreatitis and uncontrolled hypertension presented to the emergency department with glucose levels of 929 mg/dL. He reported two months of polydipsia, polyuria, and polyphagia but had no prior diabetes diagnosis despite multiple admissions for pancreatitis. Labs showed an anion gap of 13, bicarbonate of 20 mmol/L, beta-hydroxybutyrate of 2.93 mmol/L, serum osmolality of 317 mOsm/kg, urinalysis with >1000 glucose and 1+ ketones, and HbA1c of 16.4%. Blood gas showed pH 7.25 and bicarbonate 19.5 mmol/L. These findings confirmed DKA. C-peptide was low at 0.3 ng/mL, and autoimmune markers (GAD, islet cell, and zinc transporter antibodies) were negative. Ethanol level was undetectable. He was treated with insulin drip and fluids, and later transitioned to a basal-bolus regimen after anion gap closure. Discussion: While diabetes in chronic pancreatitis arises from progressive islet cell loss, it rarely presents with DKA, as residual beta-cell function generally persists until late disease. Furthermore, exocrine dysfunction usually predominates early, often preceding significant endocrine insufficiency. Our patient’s abrupt onset of symptomatic, insulin-deficient hyperglycemia leading to DKA is unusual in chronic pancreatitis. Negative autoimmune testing ruled out type 1 diabetes, and the low C-peptide confirmed insulin deficiency. This case emphasizes that in chronic pancreatitis, especially with risk factors like alcohol abuse and smoking, beta-cell loss may progress silently and culminate in acute decompensation. Clinicians should be aware of the potential for sudden, severe endocrine failure in such patients. Proactive glucose monitoring in chronic pancreatitis may help prevent life-threatening presentations like DKA. This case adds to the limited literature describing type 3c diabetes presenting initially as DKA.Presentation: Sunday, July 13, 2025

BackgroundGlycemic control in type 1 diabetes (T1D) remains a challenge, with 20−30% of adults achieving an A1c target of <7%. Glucagon-like peptide 1 receptor agonist (GLP-1 RA) and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 RA (GIP/GLP-1 RA) have emerged as a promising therapy in T1D. Previous studies have shown that patients with T1D can significantly improve glycemic control while experiencing a reduction in insulin dose and body weight when long-acting GLP-1RAs or GIP/GLP-1RAs are added to insulin therapy. However, randomized controlled trials (RCT) are still insufficient.MethodsThis is a prospective, randomized, parallel-group, open-label, superiority-controlled design that evaluates the safety and efficacy of adding tirzepatide to insulin therapy in participants with T1D under automated insulin delivery (AID) control. We will enroll 42 participants aged 18–65 years with confirmed T1D diagnosis ≥12 months, currently on AID insulin therapy for at least three months, with A1C ≥ 6.5% and ≤ 10%, and BMI ≥ 23 kg/m2. Participants will be randomized in a 1:1 ratio to either tirzepatide with a target dosage of 5.0 mg (after titration) or standard of care (SoC) for 16 weeks. The primary endpoint is continuous glucose monitoring (CGM)-measured percent time spent between 3.9 and 10.0 mmol/L (TIR) from baseline to follow-up after 16 weeks of treatment. Secondary endpoints include: the CGM-measured change in 24/7 percent time >10.0 mmol/L, > 13.9 mmol/L, < 3.9 mmol/L, < 3.0 mmol/L. The exploratory endpoints include: the change in body mass index (BMI), liver steatosis (MASLD), and body composition. Safety outcomes include severe hypoglycemia, diabetic ketoacidosis (DKA), and refractory gastrointestinal side effects.DiscussionThis is the first prospective study to investigate the safety and efficacy of tirzepatide (GIP/GLP1-RAs) as an adjuvant therapy to AID in T1D. This study may contribute unique data to significantly improving glucose and cardio-metabolic outcomes, re-directing attention to further treatment in T1D beyond insulin therapies.

Disclosure: N. Sherani: None. N. Kolta: None. D.G. Varghese: None. H.B. Whitlatch: None. R. Malek: None.Background: Development of fulminant diabetes during pregnancy, albeit a rare occurrence, has been documented in the literature. This can occur in any trimester and is characterized as Type 1B diabetes mellitus. Even pregnant patients who pass gestational diabetes screening exams can develop fulminant diabetes. The criteria for diagnosis of fulminant Type 1 diabetes include DKA within 7 days of symptom development, HbA1c< 8.5% with plasma glucose > 288 mg/dl and fasting c-peptide of < 0.3 ng/ml. Development of diabetic ketoacidosis during the third trimester can have catastrophic consequences and is associated with high fetal mortality. Clinical Case: 31-year-old female (G3P0110) with history of substance use disorder (managed with suboxone), hepatitis C, and morbid obesity (BMI >35) presented at 37 weeks and 6 days gestation with intrauterine fetal demise in the setting of severe diabetic ketoacidosis (DKA). She had no history of pregestational or gestational diabetes, and her HbA1c was 5.7% at her first prenatal visit. She had a normal oral 50 gm glucose challenge test (GCT) of 115 mg/dL at 30 weeks and 6 days, and trace urine glucose at the same visit. At 37 weeks gestation, she developed sudden-onset polyuria, polydipsia, and emesis with abdominal cramping. Fetal heart rate was undetectable. She was found to have elevated glucose (>800 mg/dL), beta-hydroxybutyrate 73.4 (0-3 mg/dL) with bicarbonate levels 9 (21-30 mmol/L) consistent with DKA. Her hemoglobin A1c was 10.5%. Further testing revealed triglyceride levels of 2,625 (<150mg/dL) that was attributed to uncontrolled hyperglycemia and propofol use. Triglyceride levels normalized after the propofol was discontinued. GAD-65, islet cell, and zinc transporter 8 antibodies were negative, and c-peptide was 0.6 (0.5-3.3 ng/mL) with glucose of 133mg/dL. Lipase was 200 (23-300 u/L). She was treated as per DKA protocol and had improvement in her clinical condition. She underwent a C-section with delivery of stillborn fetus. Autopsy of fetus revealed normal weight (2960gm) and no genetic abnormality. She continued to require basal/bolus insulin therapy as an outpatient. Conclusion: We describe a case of rapidly developing diabetes in a pregnant patient with otherwise normal antepartum testing (GCT and urine glucose), 28 lb weight gain in pregnancy, normal fetal growth, and an absence of diabetes-related symptoms until 37 weeks gestation. While this case does not meet all criteria for fulminant diabetes in pregnancy, it suggests that repeated diabetes screening should be considered in patients with high-risk clinical features, such as obesity and prediabetes, in order to avoid late-term maternal and fetal complications.Presentation: Sunday, July 13, 2025

Disclosure: F.O. Asemota: None. L. Sangurima: None. A. Sajan: None.Introduction: Rhabdomyolysis is a rare sequelae of hyperosmolar hyperglycemic state (HHS). We present a case of HHS complicated by rhabdomyolysis resulting in mortality. Case: A 73-year-old Hispanic male with hypertension and diabetes mellitus presented with lethargy after being found unconscious at home. On admission, he had tachycardia (106 beats per minute) and tachypnea (25 breaths per minute). He was unresponsive to pain or verbal commands and had dry mucous membranes. Initial investigations revealed an elevated anion gap metabolic acidosis (pH 6.938 [7.300-7.400], bicarbonate level 7.1 mEq/L [24 - 30], serum glucose 1647 mg/dL [70-99], and anion gap 37 mEq/L [7-16]. Further evaluation showed serum lactate 16 mmol/L [0.5 - 2.2], a small amount of urine ketones, and serum osmolality 422 mOsm/kg [290 - 300], establishing the diagnosis of severe diabetic ketoacidosis with hyperosmolar hyperglycemic state. Initial potassium level was normal. The patient was started on intravenous fluids and insulin drip. The electrolytes were replaced as needed. Additionally, initial blood culture showed growth of Streptococcus and Klebsiella pneumoniae for which empiric antibiotics were initiated. An electrocardiogram showed ST elevation in anterior leads, which was deemed related to demand ischemia by the cardiology team and was treated empirically with heparin. The patient had a cardiac arrest the next day and passed. A careful review of labs drawn a few hours before the arrest revealed creatine kinase of 15,432 IU/L [38 - 174], potassium 6.3 mEq/L [3.5-5.3], and phosphorus of 5.0 mg/dL [2.7 - 4.5] consistent with rhabdomyolysis which was missed. Discussion: Rhabdomyolysis is a known, rare, and usually subclinical complication of HHS precipitated by hyperosmolarity and electrolyte abnormalities. Low insulin or insulin resistance leads to decreased glucose inside the muscle cells and attenuates Na+/K+ ATPase activity. This causes accumulation of intracellular sodium and calcium due to the reduced exchange of calcium and sodium. The intracellular calcium accumulation results in the dissolution of muscle fibers causing myoglobin to be released into the bloodstream. The myoglobin in turn blocks the tubules within the nephrons, leading to severe kidney damage. In addition, insulin infusion causes a rapid shift of electrolytes into the cell, leading to hypokalemia and hypophosphatemia, which can also contribute to the development of rhabdomyolysis. Conclusion: Although most cases of rhabdomyolysis are subclinical in HHS, it has the potential to be fatal in unrecognized cases as in our patient. The early recognition of rhabdomyolysis is needed for electrolyte monitoring and careful fluid resuscitation to prevent morbidity and mortality.Presentation: Monday, July 14, 2025

Disclosure: B. Agrawal: None. S. nagpaul: None. S. Prabhakaran: None. S.A. Narra: None. H. Patel: None.Introduction: Diabetic ketoacidosis (DKA), a life-threatening complication more common in type 1 diabetes, marked by hyperglycemia, ketosis, and anion gap metabolic acidosis due to insulin deficiency. This triggers fat breakdown and ketone production. Such metabolic derangements can precipitate or exacerbate hemolysis, potentially revealing underlying conditions like G6PD deficiency. Case Presentation: A 25-year-old male with newly diagnosed insulin-dependent diabetes mellitus presented with two days of nausea, vomiting, abdominal and chest pain, polyuria, and polydipsia, following insulin non-compliance. He was tachycardic, tachypneic, and hypothermic on admission. Labs showed severe DKA (glucose 620 mg/dL, bicarbonate 5, anion gap 34, beta-hydroxybutyrate 14), HbA1c >15%, hyponatremia (125), hyperkalemia (5.9), leukocytosis (WBC 27), and elevated lactate (3.5), suggestive of pneumonia. Urinalysis revealed proteinuria and glycosuria. He was admitted to the ICU and treated with IV fluids, bicarbonate, insulin drip, and antibiotics. During hospitalization, he developed normocytic anemia with hemoglobin dropping from 13 to 6.8 g/dL, requiring transfusion. Hemolysis workup revealed elevated bilirubin, LDH, reticulocyte count, decreased haptoglobin, schistocytes on peripheral smear, and a normal hemoglobin electrophoresis. G6PD assay confirmed G6PD deficiency. After resolution of DKA, he was transitioned to subcutaneous insulin and discharged with folic acid, insulin therapy, and education on avoiding G6PD triggers. He was advised hematology and endocrinology follow-up. Discussion: G6PD deficiency compromises red blood cell (RBC) defense against oxidative stress due to impaired NADPH and glutathione production. DKA-induced acidosis and hyperglycemia increase oxidative stress, promoting RBC fragility and hemolysis. Dehydration and hyperosmolarity further reduce RBC survival. Hemolysis can present with nonspecific symptoms overlapping with DKA, delaying diagnosis. Laboratory findings include anemia, jaundice, elevated indirect bilirubin, LDH, reticulocytes, and low haptoglobin. A significant hemoglobin drop during DKA warrants investigation. A negative Coombs test helps rule out autoimmune causes, while schistocytes suggest oxidative injury. G6PD levels may appear normal during acute hemolysis due to reticulocytosis; retesting may be needed after recovery. Management includes supportive care, transfusions if needed, and avoiding oxidative triggers. Patient education and strict insulin adherence are vital to prevent recurrence. Conclusion: This case illustrates how DKA-induced oxidative stress can unmask G6PD deficiency, leading to hemolysis. Clinicians should evaluate for hemolytic anemia in DKA with unexplained anemia, especially in high-risk populations, and consider inherited enzymopathies as part of the differential.Presentation: Sunday, July 13, 2025

Disclosure: A. Gandhi: None. R. Jeun: None. S. Khan: None. C. Best: None. V.R. Lavis: None. S. Thosani: None.Objective: Diabetic ketoacidosis (DKA) is a life-threatening emergency resulting in significant morbidity and health care utilization. The most common cause of DKA in the general population is insulin nonadherence, but limited data exists on etiologies for DKA in cancer patients. In this study, we characterize the demographic and clinical characteristics of patients admitted with DKA at a comprehensive cancer center. Methods: This single-center retrospective study evaluated 91 patients with 94 admissions for DKA at our institution between January 2019 and December 2021. Demographic, clinical, and biochemical data were obtained from a review of the electronic medical record. Patient characteristics were summarized using descriptive statistics for continuous variables and categorical variables. Results: Of the retrospective cohort, 21% of patients had underlying type 1 diabetes, 48% had type 2 diabetes, and 31% had no prior history of diabetes. 46% were women with median age of 63 years. Among the 91 patients, gastrointestinal malignancies were the most common, followed by dermatological, hematological, and genitourinary malignancies. 65% of patients had metastatic or Stage IV disease at the time of hyperglycemic emergency. Of the 74 patients with baseline HbA1c levels available prior to admission, 39% had poorly controlled diabetes at baseline with HbA1c >9% (75 mmol/mol). Of patients with underlying type 2 diabetes, 24% developed euglycemic DKA secondary to SGLT2 inhibitor use, while in patients with known type 1 diabetes, lack of adequate insulin therapy remained the most common cause of DKA. In 85% of patients without any underlying history of diabetes, cancer associated drug therapy was the most common cause of hyperglycemic emergency, with immune checkpoint inhibitor(ICIs) therapy as the most frequent causative drug . Discussion/Conclusion In this study of patients admitted to a cancer center, we characterize the most common etiologies for DKA based on patient’s underlying diabetes status. This study emphasizes the need for cautious use of SGLT2 inhibitors in patients with type 2 diabetes and cancer given risk of euglycemic DKA in the setting of poor appetite. While inadequate insulin therapy was the most common cause of DKA in cancer patients with known type 1 diabetes, many of these patients were unfamiliar with how to adjust their insulin with poor oral intake associated with chemotherapy, suggesting an important opportunity for diabetes survival skills education in these patients. ICIs were a significant cause of DKA in patients without prior diabetes history, and most admissions were characterized by moderate to severe DKA on presentation, emphasizing the importance of counseling and screening patients early for this complication.Presentation: Sunday, July 13, 2025

Disclosure: A. Yousef: None. S. Gill: None. H. Osman: None. C. Xue: None. A. Shehadah: None. R. Vengilote: None. M. Quartuccio: None.Neurological complications of diabetic ketoacidosis (DKA) are less common in adults than in children, with cerebral edema being the most feared consequence. This report describes an uncommon neurological manifestation of DKA. A 32-year-old obese male, previously healthy, presented with sudden onset left leg weakness noted upon waking, accompanied by difficulty ambulating. He denied prior similar episodes. On examination, the patient was mildly confused, and neurological evaluation revealed decreased motor strength in the left lower extremity, with normal coordination and cerebellar function. Laboratory findings were significant for corrected sodium 143 mmol/L (normal 136-145 mmol/L), potassium 5.2 mmol/L (normal 3.5-5 mmol/L), bicarbonate 19 mEq/L (normal 23-28 mEq/L), venous pH 7.3 (normal 7.32 - 7.43), anion gap 25 mmol/L (normal 7-13 mmol/L), blood glucose 1084 mg/dL (normal 65-100 mg/dL), beta-hydroxybutyrate 6.53 mmol/L (normal <0.4 mmol/L), and hemoglobin A1c >15.5% (normal <5.6%). Urinalysis showed ketonuria and glucosuria, and a drug screen was negative. The patient denied recent alcohol or illicit drug use. Imaging, including a CT head, identified a 1.1 cm hyperattenuating lesion in the left parietal lobe, suggestive of intraparenchymal hemorrhage without midline shift. MRI of the brain confirmed the presence of a 1.2 cm hemorrhagic focus in the left parietal lobe, consistent with a cavernoma and possible recent hemorrhage. The patient was started on intravenous insulin per the DKA protocol and transitioned to subcutaneous insulin once DKA resolved. Further testing revealed a low C-peptide level of 0.7 ng/mL (normal 0.8-3.1 ng/mL) and elevated glutamic acid decarboxylase antibodies, consistent with autoimmune diabetes. During the hospital course, his lower extremity strength gradually improved as his blood glucose levels were better controlled. He was subsequently cleared for discharge with insulin therapy and scheduled for close follow-up at the Endocrinology clinic. This case highlights the rare occurrence of hemorrhagic stroke as a complication of DKA in adults. DKA is a pro-inflammatory state that induces vascular injury and hypercoagulability, increasing the risk of cerebrovascular events. While this association has been reported in pediatric populations, this case emphasizes the importance of recognizing such complications in adults and underscores the need for vigilance in managing severe DKA cases. This is the first known reported case in an adult.Presentation: Saturday, July 12, 2025

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiorenal risk in type 2 diabetes. However, the effect of combining these drugs remains uncertain. This systematic review aimed to evaluate the potential effectiveness and safety of combination therapy compared with monotherapy in individuals with type 2 diabetes. We systematically searched PubMed and Embase from inception to 1 May 2025 for cohort studies comparing the effect of combination therapy with SGLT2 inhibitor or GLP-1 RA monotherapy on (cardiovascular) mortality and cardiovascular or kidney endpoints in individuals with type 2 diabetes. Studies enrolling individuals with type 1 diabetes or a maximum follow-up of less than 1 year were excluded. The primary outcome was a composite of major adverse cardiovascular events (MACE). Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalisation for heart failure, a kidney composite endpoint and serious adverse events. Risk of bias was assessed with ROBINS-I. Risk ratios (RRs) and 95% CIs were pooled in random effects meta-analyses. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). We included 18 cohort studies (1,164,774 participants). In cohort studies, combination therapy was associated with a lower risk of MACE (RR 0.56 [95% CI 0.43, 0.71]; low certainty of evidence) and the kidney composite endpoint (RR 0.48 [95% CI 0.32, 0.73]; very low certainty of evidence) relative to SGLT2 inhibitor or GLP-1 RA monotherapy. Combination therapy was also associated with a lower risk of all-cause mortality (RR 0.50 [95% CI 0.40, 0.63]; low certainty of evidence), cardiovascular mortality (RR 0.26 [95% CI 0.16, 0.43]; low certainty of evidence) and hospitalisation for heart failure (RR 0.67 [95% CI 0.64, 0.71]; moderate certainty of evidence). Although safety data could not be pooled due to lack of events, no differences were observed in the risk of severe hypoglycaemia, diabetic ketoacidosis, genitourinary infections and gastrointestinal side effects. No data were reported on the risk of serious adverse events or major adverse limb events. Observational studies suggest that combining an SGLT2 inhibitor and a GLP-1 RA in type 2 diabetes may lower the risk of MACE, all-cause and cardiovascular mortality, hospitalisation for heart failure and kidney composite endpoints compared with monotherapy with either drug. Of course, residual confounding cannot be overcome but results support the need for future randomised trials of combined vs monotherapy. PROSPERO registration no. CRD42024532383.