Insulin Drip Research Articles

12599 Early Remission Of Chromosome 6 Q 24-related Neonatal Diabetes Mellitus

Abstract Disclosure: R. Pratibha: None. K. Dummula: None. Introduction: Chromosome 6q24 imprinting abnormalities represent the predominant cause of transient neonatal diabetes mellitus (TNDM), accounting for over two-thirds of cases with an estimated prevalence of 1 in 400,000. While remission typically manifests by 3 months of age, herein we detail a case of Chromosome 6q24-related TNDM exhibiting remission by 1.5 months of age. We share our clinical experience in managing this case without hypoglycemia and using C-Peptide levels as a monitoring tool to track the resolution. Case: A female infant, born at 36 weeks via elective C-section due to fetal growth restriction and oligohydramnios, was closely monitored in the nursery for potential hypoglycemia. Contrary to the expectation, she displayed escalating hyperglycemia, necessitating insulin infusion within 25 hours of birth. Apgar scores were 7 and 9, and the birth weight was 2095 g (6th percentile). Maternal history included impaired glucose tolerance in a previous pregnancy with borderline glucose tolerance during this gestation. The newborn physical exam was unremarkable except for mild macroglossia. Despite initial blood glucose (BG) of 52 mg/dl, it rose to 257 mg/dL by 16 hours. Insulin drip was started at 24 hours due to BG of 304 mg/dL. The monogenic diabetes panel obtained on day of life (DOL) #2 was negative; no acidosis was observed. The C- Peptide was low at 0.2 ng/ml. Insulin infusion was continued until DOL # 20. A trial of glyburide commenced on DOL #9 while on Insulin drip, yielded minimal response, prompting a transition to short-acting insulin for correction of hyperglycemia (>250 mg/dL). C-peptide level during sulfonylurea (SU) trial remained low (0.5 ng/mL). The infant required 2 to 3 corrections per day with 0.05 units of Lispro Insulin, with the last dose administered at 44 days. She did not receive any long-acting Insulin. As of her last follow-up at the endocrine clinic at 57 days of age, the infant is thriving well and has normal blood glucose levels. The 6q24 Methylation-MLPA study showed duplication of 6q24 on the paternally inherited chromosome 6. Significantly, she never encountered hypoglycemia during her hospital stay. The C-peptide increased to 0.8 ng/ml at DOL#37 and had normalized to 1.3 ng/mL by DOL#57 indicating remission of TNDM. Conclusion: 6q24-related TNDM may often be characterized by features such as small for gestational age (SGA), macroglossia, umbilical hernia, cardiac and renal abnormalities. Early presentation of hyperglycemia with this phenotype must prompt its diagnostic evaluation. Early resolution by 1.5 months as seen in our case is uncommon. Uniquely, we used C-peptide as a tracking tool to guide resolution and manage insulin therapy. Presentation: 6/3/2024

6660 Euglycemic DKA Induced by SGLT-2 Inhibitor Following Administration ofTirzepatide

Abstract Disclosure: K. Gurel: None. S. Mathew: None. M. Zeidan: None. S. Al Barznji: None. F. Alkhankan: None. Introduction Tirzepatide has side effects of diarrhea, nausea, vomiting, and loss of appetite(2). SGLT-2 inhibitors may cause Euglycemic Diabetic ketoacidosis(EDKA) by inducing carbohydrate starvation and volume depletion(1). Clinical Case A 72-year-old male with a past medical history of T2DM(Hg A1c 8.4[≤ 6%]) on empagliflozin, metformin, hyperlipidemia, obesity on tirzepatide who presents with complaining of nausea, vomiting, and abdominal pain. The patient noted that he started experiencing symptoms two days before admission following receiving tirzepatide dose. He takes Tirzepatide every 10 days and he was started on empagliflozin 1 month ago. The patient started to have a loss of appetite, nausea, and vomiting on the day he received his tirzepatide injection. Over the next two days, the patient’s nausea and vomiting worsened and the patient was not able to tolerate food. On admission, ABG demonstrated pure metabolic acidosis (pH of 7.24[7.30-7.40], bicarb of 11.8 [21 - 28 mmol/L] PCO2 of 27.4[ 41 - 51 mmHg]). BMP showed anion gap of 20(3-15 mmol/L) with glucose level of 145(74-106 mg/dl) . Beta-Hydroxybutyrate level was 6.3(0.0 -0.27 mmol/L). UA was only significant for glucose level of >1000(negative) and ketone level of 40(negative). Lipase level was 539(73-393 U/L). CT abdomen ruled out acute pancreatitis. No infection source was identified. Upon admission to the ICU unit, the patient was started on D5 with KCL 20 mEq and Insulin drip. The patient was followed up with a glucose check every hour and BMP every 4 hours. On day 2 of admission, the Anion gap was normalized and the insulin regimen was transitioned to subcutaneous insulin. The patient was placed on carbohydrate consistent diet. On discharge, the patient was advised to avoid taking SGLT-2 inhibitors including empagliflozin. Conclusion Tirzepatide's potential side effects, including diarrhea, vomiting, and appetite loss, may contribute to volume depletion and carbohydrate starvation(2). Individuals using both SGLT-2 inhibitors and Tirzepatide should be closely monitored for these symptoms. Reference 1-)Baggio LL, Drucker DJ. Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease. Mol Metab. 2021 Apr;46:101090. doi: 10.1016/j.molmet.2020.101090. Epub 2020 Sep 25. PMID: 32987188; PMCID: PMC8085566. 2-)Plewa MC, Bryant M, King-Thiele R. Euglycemic Diabetic Ketoacidosis. [Updated 2023 Jan 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554570/ Presentation: 6/2/2024

6984 New Onset Diabetes After Transplant: Need for Strict Glucose Monitoring

Abstract Disclosure: T. Chaudhary: None. O. Syed: None. M. Nawaz: None. R. Kaur: None. Introduction: Immunosuppressant use comes at a cost of challenging side effects, which are being discovered more as its use increases. One such example is our case of new-onset diabetes after transplant (NODAT).Patient presentation: A 36-year-old male with a past medical history of end-stage renal disease status post renal transplant (6/2023), hypertension, and hyperlipidemia who presented to the hospital in 10/2023 with fever, chills, and diarrhea. His vitals at that time were as follows: temperature 36.1C, blood pressure 148/84 mmHg, pulse 87 bpm, and a respiratory rate of 22. Lab work was significant for blood glucose 1144, anion gap 22, bicarbonate 13, potassium 7.3, Sodium 135, lipase 427, pH 7.3, urine ketones 80, HbA1C 11.5 %. CT scan of the abdomen revealed loss of peripancreatic fat and inflammatory changes surrounding the pancreas. His medication review included Tacrolimus 12 mg daily, Mycophenolate 500 mg BID, Valtrex 500mg daily, and fluconazole 200mg every other day. He was treated with 2 liters of normal saline bolus and started on maintenance fluid, and insulin drip as per DKA protocol. Calcium gluconate and an albuterol nebulizer were given for hyperkalemia. Tacrolimus and prednisone were held. Endocrinology and Nephrology were consulted. The patient was thought to have diabetes due to steroid use which were discontinued and the patient was discharged on subcutaneous insulin regimen and lower dose of tacrolimus. Despite discontinuation of steroids, patients continued to have raised glucose readings confirming the causative agent as tacrolimus. Conclusion: The current guidelines for post-kidney transplant patients recommend checking fasting blood glucose weekly for the first four weeks, then biweekly for two months, and then monthly thereafter. HbA1C should be checked every 3 months and if it is >6% then home glucose monitoring should be done as well. Although the frequency of these check-ups decreases, it is imperative for physicians to remember that patients can still develop NODAT months post-transplant. It is also essential to reinforce the importance of these glucose checks for the patient as missed diagnosis can lead to dangerous complications such as DKA. Presentation: 6/2/2024

7531 Spontaneous Coronary Artery Dissection Induced Diabetic Ketoacidosis In A Young Female: A Rare Complication Of Ketosis In A Priorly Non-Insulin Dependent Diabetic

Abstract Disclosure: F. farhat: None. P. Gonzalez: None. A.B. Ravin: None. H. Akhlaq: None. M. hossain: None. K. chalasani: None. S.W. Holland: None. R. Ong: None. J. Cheng: None. Introduction: Spontaneous Coronary Artery Dissection (SCAD) is a poorly understood and underdiagnosed condition that puts healthy young women at risk of Myocardial infarction (MI) and potential death. It occurs when a tear develops in a coronary artery. SCAD can have an atypical presentation especially in diabetic and young females; Diabetic ketoacidosis (DKA) is an uncommon, yet potentially fatal complication and can be the primary presentation in SCAD. We present a case of SCAD complicated by DKA in a non insulin dependent diabetic (NIDD).Case presentation: A 19 year old female with a past medical history of NIDDM presented to the Emergency Department with chest pain. She had troponemia and ECG revealed ST elevations. Patient was found in DKA initially. Insulin drip was started with DKA resolution in 24 hours. Hemoglobin A1c was 12.4% with negative antibody workup. Her course was complicated by SCAD found upon cardiac catheterization with unsuccessful recanalization; she was not a surgical candidate given late presentation and therefore, an intra aortic balloon pump was placed. Subsequently, she developed pericarditis and left ventricular thrombus. Discussion: SCAD is a rare condition, often presenting with acute MI and cardiogenic shock. MI may be complicated with DKA. One proposed mechanism for that is the activation of ketogenic pathways caused by excess catecholamines and cortisol; this increases physiologic stress on the body resulting in increased ketogenesis, lipolysis and free radicals causing further myocardial injury. DKA precipitated by MI increases the mortality rate to nearly 85% since the myocardium is denied glucose uptake. Signs and symptoms of SCAD are similar to MI symptoms including: chest tightness, shortness of breath and sweating. MI and SCAD can be differentiated by cardiac catheterization or by specialized contrasted CT scans. 20% of SCAD patients will experience a second episode within 5 years. Avoiding emotional stress, exercising regularly, following a healthy diet and controlling chronic conditions can help lower the risk for SCAD. Medical management is often preferred. Invasive treatments like coronary stenting or cardiac bypass may be needed if there is a complete blockage in the vessel, clinical instability or ongoing chest pain. Conclusion: SCAD is an important cause of MI in young females and can present initially as DKA in diabetics. For clinicians facing such rare cases, it is worth maintaining a broad approach to the diagnosis and treatment of these patients. The causes of SCAD remain fully unclear and genetic relations are still under investigation. Since DM type I and SCAD occur in young people, it is extremely important for clinicians to consider SCAD in the differential while managing DKA. Presentation: 6/3/2024

12431 14-year-old Presenting With Thrombocytopenia-Associated Multi-Organ Failure In The Setting Of Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome

Abstract Disclosure: N.C. Gunaratne-Breaux: None. D. Deplewski: None. Title: 14-Year-Old Presenting with Thrombocytopenia Associated Multi-Organ Failure in the setting of Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome Background: Coagulation complications are rare in hyperglycemia emergencies in children and adolescents. In patients presenting with severe and atypical hyperglycemia emergencies, special considerations need to be made to rule out life-threatening coagulopathy. Clinical Case: A 14-year-old male with history of Type 1 Diabetes presented in severe Diabetic Ketoacidosis/Hyperosmolar Hyperglycemic Syndrome overlap. Initially had severe hypotension and altered mental status concerning for cerebral edema. Initial venous blood gas showed pH of 6.82, pCO2 17.1, and HCO3 2.8, serum glucose was 1375 mg/dL, serum ketones >7.00 mmol/L, and serum osmolality was 384 mOsm/kg. Once insulin drip was started, glucose, ketones, and serum osmolality improved, but patient continued to be encephalopathic and had worsening tachypnea and desaturations. Patient was eventually intubated. After intubation, patient’s acidosis improved, but patient developed kidney failure (prompting initiation of dialysis), liver injury, decreased cardiac function, and high inflammatory state. A comprehensive multi-specialty team including pediatric intensive care, infectious diseases, rheumatology, neurology, and cardiology were involved in the care. On day three of admission, patient had multiple areas of ischemia on fingertips and ear and clotting of multiple IV and dialysis catheters, prompting a coagulopathy evaluation. Labs showed microcytic anemia (hemoglobin 10.0 g/dL; mean corpuscular volume 75fL), thrombocytopenia (platelet count 17 10e3/uL), coagulopathy (prothrombin time 16.8 sec, INR 1.3, prolonged thrombin time 48.8 sec), and elevated ferritin (507 ng/mL). Given labs and multi-organ involvement, determined by hematology to be Thrombocytopenia Associated Multi-Organ Failure (TAMOF). Patient was started on plasmapheresis and had dramatic improvement – was eventually extubated and returned to neurologic baseline without any notable deficits. Multi-specialty team ruled out all other possible causes of TAMOF; determination that the TAMOF developed secondary to DKA/HHS. Conclusion: Hyperglycemia emergencies can lead to a hyperinflammatory state that can lead to disruption of the coagulation cascade, including disseminated intravascular coagulopathy or thrombotic thrombocytopenia purpura. There have been rare reports of thrombocytopenia associated multi-organ failure provoked by DKA, thought secondary to critical illness mediated low ADAMST13 levels. This is a novel case of TAMOF caused by DKA/HHS overlap syndrome. It is important to screen for coagulopathy in cases of patients with DKA or DKA/HHS who do not show clinical improvement with resolution of ketosis and hyperosmolarity. Presentation: 6/2/2024

7491 Post operative Euglycemic Diabetic Ketoacidosis in Type 2 Diabetic patient - A diagnostic challenge

Abstract Disclosure: S. Azmat: None. O. Lodhi: None. H. Ashok: None. M.F. Siddiqui: None. Euglycemic Diabetic Ketoacidosis (EDKA) is a rare but potentially fatal condition that is often difficult to diagnose as underlying ketoacidosis is masked by euglycemia. The diagnosis and management of this condition requires a swift and comprehensive approach to avoid delay. We report a case of 66-year-old female with Insulin-dependent Type 2 DM who developed postoperative euglycemic diabetic ketoacidosis, highlighting the significance of maintaining a high degree of suspicion for EDKA in postoperative patients, whose surgical course may obscure the underlying diabetic ketoacidosis symptoms. Clinical Case: A 66-year-old female with past medical history of Insulin dependent Type 2 DM presented to the emergency department with severe epigastric pain. CT Abdomen revealed perforated gastric ulcer with pneumoperitoneum requiring urgent laparoscopic graham patch repair. Patient’s outpatient medications include Lantus and metformin. She had mild hyperglycemia on admission with blood glucose of 176 mg/dL (140-160mg/dL) without metabolic abnormality. Insulin administration was omitted due to pre and post operative normoglycemia. The patient was NPO followed by initiation of nasogastric tube feeds. Postoperative course was complicated by hypotension, generalized abdominal discomfort and anion gap metabolic acidosis. Graham patch failure, abdominal infection, and post-surgical complications were systematically ruled out. Patient continued to decline with worsening anion gap metabolic acidosis; pH of 7.18 (7.35-7.45), HCO3 < 10 mEq/L (21 mEq/L - 31 mEq/L), anion gap15 mmol/L (8 to 12 mmol/L), blood sugar (147-208 mg/dl). There was no lactic acidosis or renal impairment. Beta hydroxybutyrate levels were elevated at > 4.5 mmol/L. Thus diagnosis of euglycemic DKA was established and treated with insulin drip per DKA protocol and dextrose fluids. EDKA resolved within five days with clinical improvement. She was transitioned to subcutaneous basal bolus insulin. She remained euglycemic and and had good surgical outcomes.Discussion: Euglycemic DKA is rare with only 2.6% to 3.2% of DKA, presenting as euglycemic. It presents as unique diagnostic challenge due to atypical DKA presentation with blood glucose less than 250 mg/dL. The primary driver for EDKA is either a reduction in hepatic glucose production at times of fasting or the overabundance of counter-regulatory hormones resulting in excess glucosuria. Literature has reported the effects short-term fasting on developing EDKA and starvation induced ketosis secondary to extreme ketogenic diets or bariatric surgery primarily among Type 1 diabetics. Clinically patients may exhibit symptoms similar to classic DKA, however, this classic picture may be confounded in a critically ill post-surgical patient, thus delaying recognition. This emphasizes the importance of including EDKA in differentials while evaluating such patients. Presentation: 6/1/2024

5175 A Rare Case of Type B Insulin Resistance Syndrome

Abstract Disclosure: S. Fatima: None. A. Champion: None. S. Ward: None. Q. Aziz: None. K.E. Izuora: None. Introduction: Severe insulin resistance may be defined as a severely diminished response to insulin’s biological effects and is characterized by substantial hyperinsulinemia and impaired glucose response to endogenous and exogenous insulin. We hereby present a rare case of Type B Insulin Resistance Syndrome (TBIRS). Case:40-years old female with history of systemic lupus erythematosus (SLE), diabetes mellitus was admitted with multiple rheumatologic complaints, including arthralgias, oral ulcers, skin rash, and hair loss secondary to SLE flare. Endocrinology was consulted for diabetes management. Her HbA1c had increased from 7.3% to 11.6% in 3 months despite taking Glargine 45 units daily, Lispro 15 units pre-meals and metformin. She noticed 80 lbs weight loss for past 6 months. Her BMI was 26 and exam showed acanthosis of neck, armpits, groin, hair loss on scalp, multiple genital ulcers, and facial rash. She was noted to have refractory hyperglycemia despite high insulin doses. By 14th day of hospitalization, she was on 287 units of insulin (3.4units/kg) daily. We suspected TBIRS in the setting of SLE. Metformin and pioglitazone were started. Further testing showed insulin level 152mIU/ml (2.6-14.9mIU/ml), C-peptide 1.7 ng/ml (1.1-4.4 ng/ml), islet-cell antibody negative, GAD-65 antibody <5 u/ml, insulin antibody 6.5 uU/ml, IGF-1 14 (79-259 ng/ml), adiponectin 13.3 (2.4-17.9 ug/ml), testosterone 7 (8-60 ng/dl), free testosterone <0.2 (0-4.2 pg/ml), total cholesterol 200 mg/dl (<200 mg/dl), triglycerides 85 mg/dl (<150 mg/dl), LDL 154 mg/dl (<100 mg/dl), HDL 29 mg/dl (>60 mg/dl). She was transferred to National Institute of Health for further care. She was confirmed to have TBIRS by insulin receptor antibody testing, started on regular insulin U500 initially, and then switched to IV insulin drip requiring up to 1700 units of insulin per hour. She received methylprednisolone, cyclophosphamide (2 doses), rituximab (2 doses), hydroxychloroquine and IV immunoglobulin. Her stay was complicated by hemophagocytic lymphohistiocytosis. She was discharged on U-500 Regular insulin, 1000 units with breakfast and 500 units with lunch, Prednisone 60 mg daily and Hydroxychloroquine. Two months later she was found unresponsive at home secondary to hypoglycemic seizures. She required dextrose drip and was discharged on Glargine 16 units and Lispro 6 units with meals. Conclusion: TBIRS is caused by a highly specific polyclonal autoantibody against the cell surface insulin receptor that decreases the cellular insulin response and causes refractory hyperglycemia. About 100 cases have been reported in literature. 60% of the cases are associated with SLE. The goal of therapy is to reverse the hypercatabolic state with high doses of insulin and to eliminate the autoantibodies with immunosuppressive therapy. The most common cause of mortality is hypoglycemia. Presentation: 6/3/2024

12315 Unveiling A Paraganglioma: Catecholamine-Induced Hyperglycemia Masquerading As Type 2 Diabetes Mellitus

Abstract Disclosure: S. Salman: None. M. Hussine: None. J. Tibaldi: None. Background: Excessive catecholamines have been demonstrated to exert adverse effects on insulin homeostasis and carbohydrate metabolism, potentially resulting in the onset of secondary DM. We present a case of a patient who had been previously misdiagnosed with T2DM for an extended period. Clinical Case: A 34-year-old woman with history of T2DM, HTN, and chronic tachycardia on beta blockers, presented with complaints of palpitations, headaches, and abdominal pain for two weeks. Upon admission, she was found to be in DKA, necessitating transient administration of insulin drip. Furthermore, she exhibited persistent tachycardia and intermittent episodes of hypertensive urgency. Notably, thyroid levels revealed euthyroidism. Although DKA resolved, her fasting blood sugar levels remained elevated and refractory to escalating insulin therapy. CT abdomen with contrast revealed a large enhancing mass in the RUQ. MRI abdomen confirmed an 8.1 cm heterogeneously enhancing T2 hyperintense mass located in the RUQ, abutting the right hepatic lobe, right adrenal gland, extrahepatic biliary ducts, and adjacent vessels. Given suspicions of a neuroendocrine tumor, she was transferred to the surgical service for tumor excision. Hormonal analysis revealed elevations in plasma metanephrines (620 pg/mL, n 0-88 pg/mL), plasma normetanephrines (9954 pg/mL, n 0-210.1 pg/mL), 24-hr urine normetanephrines (10,952 μg/24hr, n 110-720 μg/24hr) and 24-hr urine metanephrines (1406 μg/24hr, n 35-278 μg/24hr). Additionally, she exhibited elevated 24-hr urine epinephrine fraction (218 μg/g Cr, 0-20 μg/g Cr) and 24-hr urine norepinephrine fraction (2775 μg/g Cr, 0-45 μg/g Cr). Preoperatively, appropriate alpha and beta blockade were administered, followed by successful retroperitoneal tumor resection. Postoperatively, her glucose levels normalized without the need for further insulin therapy, and no episodes of hypoglycemia were reported. Histopathological examination of the excised mass revealed an 11 cm sympathetic paraganglioma with retention of SDHB staining. Genetic testing for SDHB, SDHD, VHL, and RET mutations is pending. Conclusion: This case underscores the potential oversight of pheochromocytomas and paragangliomas due to their nonspecific symptomatology, often mimicking more prevalent conditions, thereby presenting diagnostic challenges. The catecholamines secreted by these tumors can lead to both impaired insulin secretion and increased insulin resistance, resulting in clinically significant manifestations. The exact mechanism underlying the glycemic dysregulation remains controversial, necessitating further investigation through large-scale multicenter prospective studies to enhance understanding and inform diagnostic and therapeutic strategies for these tumors, which can manifest with severe and potentially fatal glycemic disturbances. Presentation: 6/1/2024

12615 Extremely High-dose Insulin Requirement In A Child With Covid-19 Infection

Abstract Disclosure: R. Pratibha: None. T.R. Langner: None. Background: COVID-19 infection has been associated with new diagnosis of diabetes, worsening of hyperglycemia, and increased frequency and severity of diabetic ketoacidosis (DKA) in type 1 diabetes (DM) patients. Stress- related and steroid induced hyperglycemia are also well described during COVID infection with poor glycemic control being linked to more severe SARS-CoV-2 infection outcomes. While insulin needs increase during infection, extremely high insulin requirement is uncommon and not described in the pediatric population. We present here a case of mild COVID infection with transient markedly high insulin requirements. Clinical Case A 16-year-old-African-American- female with history of fairly well controlled type 2 diabetes mellitus on closed loop system insulin pump (Omnipod) with continuous glucose monitor (CGM), was admitted with COVID-19, aspiration pneumonia and hyperglycemia. She had been diagnosed 10 months prior with Hemoglobin A1c (HbA1c) of 11.4% and mild diabetic ketoacidosis (DKA). Diabetes antibodies were negative. Four months prior to admission her HbA1c was 7.8%. Upon this hospitalization she had no hypoxemia or respiratory failure and did not need steroids. Procalcitonin level 0.09 ng/mL was normal. Developmental delay, non-ambulatory and non-verbal status, an underlying mitochondrial neurological disease with G tube and ventilator dependence added to the medical complexity. HbA1c (8.1%) and Fructosamine 316 (n 200-285 mcmol/L) were not indicative of poor control. While her pneumonia resolved promptly, blood sugar (BG) elevation prolonged her hospitalization. She was not in DKA. Despite increasing her basal rate by 50% and an additional 20% higher temporary basal rate via her insulin pump there was little response. She was switched to Insulin drip by the 7th day. Her Insulin rate had increased to 26 units per hour (at 0.64 Units/Kg/hour) by day 8. This high insulin-dose need lasted for around 36 hours, before gradually reducing over a week. She has a history of recurrent pancreatitis. Lipase 335 U/L was elevated initially but started reducing within 2 days and had normalized by day 13. She was transitioned back to her pump although at higher basal rate than the previous home regimen, by 14th day. Conclusion While a constellation of factors such as stress, steroids, underlying poor glycemic control may cause hyperglycemia in COVID-19, these do not explain the high insulin demand in our patient. COVID infection with impaired insulin secretion, mild pancreatitis may have contributed to the brief remarkably high-dose insulin requirement, but it appears to be increased insulin resistance which could possibly explain the transient derangement. To our knowledge this has previously not been described in a pediatric diabetic patient. Presentation: 6/3/2024

6588 Insulin Autoimmune Syndrome Presenting with Severe Insulin Resistance and Recurrent Diabetic Ketoacidosis

Abstract Disclosure: E. Looi: None. R. Rosenberg: None. S. Sugar: None. H. Stone: None. A.W. Michels: None. D. Saxon: None. Background: Insulin autoimmune syndrome (IAS) is a rare cause of severe insulin resistance and is typically associated with intermittent hypoglycemia due to insulin antibodies (IA) with high binding capacity and low insulin affinity. However, consideration should be given for atypical presentation of IAS or co-presentation of IAS with type B insulin resistance syndrome (TBIRS) in the absence of hypoglycemia, as described in this case. Case: A 78-year-old African American female (BMI 21 kg/m2) with poorly controlled type 2 diabetes (A1c 11%) experienced recurrent episodes of diabetic ketoacidosis (DKA) despite adherence to escalating insulin doses (310 units daily, 5 u/kg/day). She was referred to endocrinology and continuous glucose monitoring revealed consistently elevated glucose levels (300-400 mg/dL) without hypoglycemia. She had normal renal function, hepatic function, and lipid panel. During a subsequent hospitalization, she required insulin drip rates of 50-70 u/hr. Insulin resistance workup revealed significantly elevated IA level (8.346, normal ≤ 0.010) measured using a fluid-phase radiobinding assay with high insulin binding capacity (1040 U insulin-binding/L blood) and low insulin binding affinity (1.9x107 M), which supported the diagnosis of IAS. Rheumatologic workup for other autoimmune diseases was negative. Due to recurrent DKA episodes, severe insulin resistance without obvious alternative cause, and lack of hypoglycemic events despite low IA binding affinity, co-morbid TBIRS was considered. As there are no commercially available insulin receptor antibody (IRAb) assays, diagnosis could not be confirmed before her condition worsened, and she was admitted for another episode of DKA within a week of being discharged. Due to clinical deterioration and high suspicion for IAS ± TBIRS, treatment with a combination of immunosuppressive agents was initiated in accordance with an NIH protocol (Klubo-Gwiezdzinska J, et al. 2018). Intravenous immune globulin (0.5g/kg/day) was administered over 2 days which resulted in a brief reprieve and followed by significant relapse. Two doses of rituximab (750 mg/m2) and 2 steroid pulses (dexamethasone 40 mg PO daily for 4 days) were then administered 2 weeks apart. Cyclophosphamide 100 mg daily was also started. Her hyperglycemia and insulin requirements subsequently improved, and she was eventually discharged with good glycemic control on a total daily dose of 40 units of insulin (0.5 u/kg/day), an 87.1% reduction in daily insulin requirement. Conclusion: This case demonstrates that IAS - although classically associated with hypoglycemic episodes - may also present with severe insulin resistance and recurrent DKA without hypoglycemia. Whether characterized by high IA binding capacity and affinity or coexisting with IRAb, a combination of immunosuppressants proved effective in treating both TBIRS and IAS in this instance. Presentation: 6/3/2024

7672 Ketosis-Prone Diabetes - A Case Series

Abstract Disclosure: T. Ismail: None. A. Farooq: None. G. Acharya: None. J. Snitzer: None. Introduction Ketosis-prone diabetes (KPD) is a syndrome that primarily affects African Americans. It is characterized by ketoacidosis, which is like Type 1 Diabetes Mellitus (T1DM). KPD is unique because it lacks identifiable autoimmunity and has a relative insulin deficiency, resembling Type 2 Diabetes Mellitus (T2DM). Therefore, KPD is informally classified as Type 1.5 Diabetes Mellitus. However, the clinical course and outcomes of KPD are like those of T2DM, and managing blood sugar levels is possible through non-insulin antidiabetic medications and dietary interventions. Case Series: Our study involved six patients who were all of African-American ethnicity. There were an equal number of male and female patients, with ages ranging from 21 to 61 years. One patient had a BMI of 27.2, which is considered overweight, while the rest had a BMI in the obese category ory(BMI>30). Two out of six patients had a pre-existing diagnosis of type 2 diabetes mellitus (T2DM) before the initial diabetic ketoacidosis (DKA) event. One patient had prediabetes. All patients required hospitalization for ketoacidosis and hyperglycemia and were found to have a glycated hemoglobin (HbA1c) level of more than 10% during these DKA events. All patients received intravenous hydration and insulin drip treatment and were discharged with a combination of long and rapid-acting insulin regimens. Following the resolution of the first episode of diabetic ketoacidosis (DKA), all six patients experienced a decrease in their insulin requirements for optimal glycemic control. Currently, four patients have discontinued insulin entirely. Moreover, all six patients tested negative for the presence of GAD-65, insulin, and islet antigen-2 antibodies. Among the patients, only one had a previously established autoimmune disease, i.e., inflammatory bowel disease. None of the patients experienced a repeat episode of diabetic ketoacidosis. Conclusion: It is important to note that not all patients who present with Diabetic ketoacidosis have Type 1 Diabetes Mellitus (T1DM). Hence, checking auto-antibodies for T1DM before making a final diagnosis is crucial. C-peptide levels may not accurately reflect the degree of relative permanent insulin deficiency in this population if measured during or immediately after an episode of diabetic ketoacidosis due to glucose toxicity and other factors. Given its prevalence in obese individuals, weight loss through dietary modifications and GLP-1 receptor analogs may be beneficial. Presentation: 6/3/2024

Evaluation of a Standardized Obstetrics Insulin Drip Protocol and Order Set

Objective The prevalence of pregnancies affected by diabetes is increasing, with the Centers for Disease Control and Prevention reporting that 1–2% of pregnant women have type 1 or type 2 diabetes and up to 10% of pregnancies are affected by gestational diabetes as of 2018. Maternal glycemic management is directly related to fetal and neonatal outcomes, and aberrant maternal hyperglycemia has known negative outcomes. Although most of glycemic management centers on outpatient treatment, evidence exists to support the use of intravenous insulin drips during inpatient admissions. This study aimed to evaluate an intravenous insulin protocol specific to the obstetric (OB) population. Research Design and Methods This was a single-center retrospective pre-/post- cohort study of OB patients with diabetes admitted to an academic medical center. Groups were differentiated based on admission date and protocol implementation with a 6-month washout period. Included patients received an intravenous insulin drip around either antenatal corticosteroid administration or during labor and delivery. Those who were within 7 days of receiving a diabetic ketoacidosis diagnosis or who were admitted to an intensive care unit were excluded. Results Fifty-nine patients received 69 distinct insulin drip orders. Twelve drips were included in the group admitted before initiation of the insulin drop protocol (pre-group) and 57 in the group admitted after the protocol went into effect (post-group). Time spent within the goal glucose range while on an insulin drip in the pre-group was 1.63% compared with 39.30% in the post-group (P <0.001). Glucose levels <70 mg/dL was 0.00% in the pre-group compared with 3.23% in the post-group (P = 0.045). There were no differences in severe hypoglycemia (glucose <50 mg/dL), hyperglycemia (glucose >110 mg/dL), or neonatal outcomes. Conclusion Implementation of a nursing-driven, obstetrics-specific intravenous insulin drip protocol significantly improved maternal glycemic management within a goal glucose range of 70–110 mg/dL during antenatal corticosteroid administration and labor and delivery.

Permissive intrapartum glucose control: an equivalence randomized control trial (PERMIT)

BackgroundThere is limited high quality data to determine best practices for maternal blood glucose management during labor. ObjectiveWe compared permissive care (target maternal blood glucose 70–180 mg/dL) to usual care (blood glucose 70–110 mg/dL) among laboring individuals with diabetes. Study DesignThis was a two-site equivalence randomized control trial for individuals with diabetes (pregestational or gestational) at ≥ 34 weeks in labor. Individuals were randomly allocated to usual care or permissive care. Maternal blood glucose was evaluated by capillary blood glucose monitoring in latent and active labor every 4 and 2 hours. Insulin drip was initiated if maternal blood glucose exceeded the upper bounds of the allocated target. The primary outcome was first neonatal heel stick glucose within two hours of birth before feeding. We assumed a mean first neonatal blood glucose of 50 ±10 mg/dL. To ensure that the use of permissive care did not increase or decrease the first neonatal blood glucose >10 mg/dL (two-tailed, α= 0.05, β= 0.1), 96 total participants were required. We calculated adjusted relative risk (aRR) and 95% confidence intervals (CI) in an intention-to-treat analysis. A Bayesian analysis was preplanned to estimate the probability of equivalence with a neutral informative prior. ResultsOf 511 deliveries with diabetes assessed for eligibility (10/2022 - 6/2023), 280 (54.8%) met eligibility criteria, and 96 (34.3%) agreed and were randomized. In the usual care group, 17% required an insulin drip compared to none in permissive care. There was equivalence in the primary outcome between usual and permissive care (57.9 vs. 57.1 mg/dL, adjusted mean difference -0.72, 95% CI -8.87,7.43). Bayesian analysis indicated 98% posterior probability of mean difference not being greater than ±10 mg/dL. The rate of neonatal hypoglycemia was 25% in the usual care group and 29% in permissive group (adjusted relative risk 1.14, 95% CI 0.60, 2.17). There was no difference in other neonatal or maternal outcomes. ConclusionIn this randomized control trial, while almost 1 in 6 individuals with diabetes required an insulin drip with usual intrapartum maternal blood glucose care, permissive care was associated with equivalent neonatal blood glucose.

Evaluation of a Protocol Change Promoting Lactated Ringers Over Normal Saline in the Treatment of Diabetic Ketoacidosis.

Current guidelines recommend normal saline (NS) for fluid resuscitation in the management of patients presenting with diabetic ketoacidosis (DKA). However, previous prospective studies have demonstrated improvement in patient-specific outcomes, including time to DKA resolution, when balanced crystalloid fluids are used. We conducted a single institution, retrospective cohort study of adult patients admitted with DKA before and after a protocol change within our institution, which shifted the default resuscitative and maintenance fluid in our DKA management protocol from NS to lactated Ringer's solution (LR). The primary outcome was time from DKA clinical presentation until DKA resolution. The secondary outcome was time to discontinuation of DKA protocol insulin drip. Of 246 patients meeting inclusion criteria, 119 were in the NS group (preprotocol change, where NS was the default resuscitative fluid) and 127 to the LR group (postprotocol change, where LR was the default resuscitative fluid). Time to DKA resolution was significantly decreased in the LR group (mean = 17.1 hours; standard deviation [SD] = 11.0) relative to the NS group (mean = 20.6 hours; SD = 12.2; P = .02). Duration of DKA protocol insulin drip was shorter in the LR group (mean = 16.0 hours; SD = 8.7) compared with the NS group (mean = 21.4 hours; SD = 12.5; P < .001). In this retrospective cohort study, protocolized DKA intravenous fluid management with LR resulted in shorter time to resolution of DKA and reduced duration of DKA protocol insulin drip.

Peak insulin drip rate associated with decreased infections post-solid organ transplant.

Infection and rejection outcomes were retrospectively analyzed in patients following liver transplant and separately following heart transplant with patients being stratified by their severity of immediate postoperative insulin resistance as measured by the peak insulin drip rate that was required to reduce glucose levels. For each group, these peak insulin drip rates were divided into quartiles (Q). In liver transplant patients (n=207), those in Q4 (highest infusion rate) had significantly fewer infections up to 6 months post-transplant (42.3%vs. 60.0%, p=.036) and borderline fewer rejection episodes (25.0%vs. 40.0%, p=.066) compared to Q1-Q3 patients. To confirm these unexpected results, a subsequent similar analysis in heart transplant (n=188) patients again showed that Q4 patients had significantly fewer infections up to 6 months (19.1%vs. 53.9%, p<.0001) compared to Q1-Q3 patients. Logistic regression in a subset of 103 cardiac transplant patients showed that the maximum glucose during surgery, prior MI, and hypertension were associated with severe insulin resistance (SIR) status, while the presence of pre-existing diabetes and BMI were not. We hypothesize that patients are who are able to mount a more robust counter-regulatory response that causes the insulin resistance may be healthier and thus able to mount a better response to infections.

Improvement of renal functions, graphene-induced rapid progression of prediabetes in an elderly woman with arthritis by graphene-exfoliator NaCl with KCl solution, 3 cases

A 81-year-old female presented with two weeks of fatigue, dysuria, abdominal pain, and weight loss. Vital signs and physical exam were normal except for abdominal tenderness and dry oral mucosa. Complete Blood Count (CBC) was normal; blood glucose was elevated. She received an insulin drip, normal saline, and potassium. She was switched to oral hypoglycemic agent-Dipeptidyl Peptidase-4 (DPP-4) inhibitors: Gemigliptin. Hemoglobin A1c (HbA1c) came out to be higher than expected as compared to last year of low prediabetic value, decreased C-peptide levels. Her first abnormal HbA1c was 5.9% a year ago. She was recieved intramuscular injection with graphene a year ago. Type I Diabetes Mellitus (DM) passes from autoimmunity positive normoglycemia to dysglycemia to the symptomatic stage. Mechanisms could be cytokine-mediated beta-cell damage or autoimmunity as a part of autoimmune syndrome induced by lipid nanoparticles including graphene. This case reports blood glucose by graphene-exfoliator NaCl with KCl solution on the rapid progression of prediabetes to Type 1 DM.

THU387 Euglycemic Diabetic Ketoacidosis And SGLT-2 Inhibitor Use

Abstract Disclosure: N. Abrahimi: None. A. Abrahimi: None. N. Terrigno: None. Background: Diabetic ketoacidosis (DKA) is a known adverse effect of SGLT-2 inhibitors. (1) Incidences of euglycemic diabetic ketoacidosis in patients on SGLT-2 inhibitors are reported on less. Clinical Case: A 39-year-old male past medical history of uncontrolled, non-insulin dependent diabetes mellitus and pancreatitis who presented with abdominal pain, nausea and coffee ground emesis. On initial work up, basic metabolic panel showed blood glucose level of 175 mg/dL with an elevated anion gap of 22 mmol/L. Initial differentials included suspicion for euglycemic diabetic ketoacidosis or acute intraabdominal pathology. Venous blood gas showed metabolic acidosis, with a pH of 7.21 and bicarbonate of 9.7 mmol/L, beta hydroxybutyrate was elevated at 7.83 mmol/L. CT abdomen pelvis found a small hiatal hernia, gastric wall thickening, likely gastritis, and was negative for other intraabdominal pathology. Home medications of the patient included dapagliflozin, semaglutide, metformin, gabapentin, and pantoprazole. Patient was admitted with the diagnosis of suspected euglycemic diabetic ketoacidosis and was started on an insulin drip along with D5 0.45 normal saline. Patient’s anion gap was monitored with basic metabolic panel orders every two hours. The insulin drip was discontinued once the patient had two consecutive normal anion gaps and the patient was subsequently started on a subcutaneous insulin regimen. Conclusion: SGLT-2 inhibitors may cause euglycemic diabetic ketoacidosis based on the physiology of the SGLT-2 transporter and the pharmacology of the SGLT-2 inhibitors. (2) Clinical importance of this case report is to consider euglycemic diabetic ketoacidosis in patients on SGLT-2 inhibitors presenting with nausea, vomiting with normal blood glucose to not delay in the diagnosis and treatment of this life-threatening condition.

SAT086 Early-onset HNF1B-MODY With Persistent Insulin Requirement In A 2-year-old Female

Abstract Disclosure: F. Ighalo: None. S.R. Kelly: None. M. Tosur: None. M.E. Craven: None. Introduction: Diabetes related to HNF1B pathogenic variants or deletions (maturity-onset diabetes of the young 5 [MODY 5]) typically presents in adolescence or early adulthood, with a median age of 20 years. Bustamante et al. previously described two patients with 17q12 deletion encompassing HNF1B presenting with diabetes and pre-diabetes before the age of 3, who were managed with dietary intervention alone without insulin requirement. This case describes a 2-year-old diagnosed with HNF1B-MODY after developing hyperglycemia in the setting of an acute illness, who continued to require insulin therapy following recovery. Clinical Case: A 2-year-old female with a history of recurrent viral infections and failure to thrive was admitted to the intensive care unit in hypovolemic shock due to hemolytic uremic syndrome due to Shiga toxin. On hospital day 7, while on supraphysiologic steroid doses, she developed hyperglycemia with glucoses above 600 mg/dL. She required an insulin drip to maintain blood glucoses between 100 and 200 mg/dL. Her four-month hospital stay was complicated by cardiogenic shock requiring extracorporeal mechanical oxygenation, renal failure requiring hemodialysis, respiratory failure resulting in a tracheostomy, and dysphagia resulting in a gastrostomy tube. During this time, she continued to require insulin despite being weaned off steroids and transitioning from total parenteral nutrition to gastrostomy tube feeds. Her hemoglobin A1c one month post-diagnosis was 4.9%, and continued to rise to 6.6% and 7.6% at 3 and 4 months post-diagnosis, respectively. Testing for islet autoantibodies was negative. A chromosomal microarray analysis revealed a micro-deletion in chromosome 17q12 that included the HNF1B gene. MRI showed a near total absent pancreas, and multiple small cysts scattered throughout both kidneys. She also had fecal elastase levels in the insufficient range (135 mcg/g, normal &amp;gt;200 mcg/g). Six weeks after the start of insulin drip, she was transitioned from an insulin drip to subcutaneous insulin injections, and eventually placed on an insulin pump prior to discharge. With continued clinical improvement, her insulin doses decreased, but she was not able to come off insulin completely. She had gradual decline in her insulin requirements from 1.0 units/kg/day down to 0.1 units/kg/day at time of discharge. Her current insulin requirement at 6 months post-diagnosis is 0.2 units/kg/day. Conclusion: This case represents the rare development of diabetes before adolescence in HNF1B-MODY, and one of the most severe presentations seen in a prepubertal child requiring persistent insulin therapy at 6 months post-diagnosis. Potential contribution of complicated hospital course on persistent insulin requirement in the setting of 17q12 micro-deletion cannot be excluded. Presentation: Saturday, June 17, 2023

THU016 Hiding In Plain Sight: Florid Cushing’s Disease Presenting As A Severe Extremity Cellulitis

Abstract Disclosure: C.M. Godar: None. E.B. Noble: None. N.O. Vietor: None. T.S. Knee: None. Background: Cushing’s syndrome may rarely present as an emergency known as Florid Cushing’s Syndrome. Patients can exhibit severe hyperglycemia, hypertension, hypokalemia, infections, and hypercoagulability. Cushing’s syndrome is a rare disease, and the constellation of clinical features can be overlooked if clinicians are not aware of the manifestations of hypercortisolism. We present the case of a patient with Cushing’s syndrome that went unrecognized with life-threatening sequelae. Case presentation: A 52-year-old woman with well-controlled type 2 diabetes and hypertension was admitted to the hospital for severe left lower extremity cellulitis. Prior to hospitalization she had noted rapid weight gain, fatigue, weakness, mental clouding, and moodiness. She was admitted for antibiotics and surgical debridement. The infection persisted despite broad spectrum antibiotics, multiple surgical debridements, and skin grafting. She became bacteremic, and extremity amputation was considered. She additionally developed hypertensive emergency, refractory hypokalemia, and hyperglycemia to 396 mg/dL. Exam was notable for facial plethora, supraclavicular fullness, dorsocervical fat pad, and violaceous abdominal striae. Cushing’s Syndrome was suspected, and labs revealed a significantly elevated random serum cortisol of 60.5mcg/dL (Ref 6.2-19.4), significantly elevated 24H urine cortisol of 2157mcg/24H (Ref 0-50), and ACTH elevated to 81.8pg/mL (Ref 7.2-63.3) that confirmed Cushing’s Disease. MRI sella and octreotide scans did not localize a lesion. Inpatient therapy included multiple antihypertensive agents, insulin drip, aggressive potassium repletion, and initiation of ketoconazole to reduce cortisol levels. Ketoconazole was maximally dosed and she underwent surgical exploration and removal of a small pituitary microadenoma. Following surgery, she developed transient adrenal insufficiency requiring hydrocortisone and she no longer required antihypertensives, insulin, or potassium therapy. Follow up 7 years later has revealed no recurrence of Cushing’s Disease. Discussion: Cushing’s Syndrome may present with a variety of clinical features and rarely may present as a medical emergency. Delay in diagnosis can lead to Florid Cushing’s Syndrome which carries high risk for morbidity and mortality. This case illustrates the need for clinician awareness of the features of Cushing’s Syndrome: hypertension, hyperglycemia, rapid weight gain, cushingoid exam features, hypokalemia, hirsutism, virilization, infection, and/or hypercoagulable state. Severe hypercortisolism was responsible for this patient’s refractory infection, and if not controlled, she likely would have endured a lower extremity amputation. Rapid detection with elevated random serum and/or urine cortisol and treatment with a cortisol-lowering agent is critical and lifesaving. Presentation: Thursday, June 15, 2023

THU350 Rapid Decrease Of Glycemic Levels In Three Patients With Severe Insulin Resistance Associated With Bell’s Palsy.

Abstract Disclosure: E. Chuki: None. M. Lightbourne: None. B. Abel: None. R.J. Brown: None. Bell’s palsy (BP) is associated with diabetic angiopathy and facial nerve ischemia and may be the first sign of diabetic mononeuropathy. Specific risk factors for diabetic mononeuropathy have not been well established. Rapid tightening of glycemic control has been associated with worsening diabetic retinopathy. However, this association has not been reported previously in the development of diabetic mononeuropathy or BP. We describe three patients with extreme insulin resistance, in whom rapid correction of hyperglycemia was temporally associated with development of BP. Case 1: A 63 year-old African American male with history of type 2 diabetes (T2D) and peripheral neuropathy was admitted with sudden onset severe insulin resistance and DKA, leading to a diagnosis of type B insulin resistance. Serum glucose was &amp;gt;600 mg/dl and A1c was 13.4%. He was treated with an insulin drip, then transitioned to subcutaneous insulin U-500 at a total daily dose of ∼3000 units, resulting in blood glucose between 140 and 180 mg/dl. On Day 5 after initiating U-500 and achieving tight control of glycemia, the patient developed bilateral Bell’s Palsy, which resolved after 4 years. Case 2: A 25 year-old African American female with history of T2D was admitted with sudden onset severe insulin resistance and DKA requiring an insulin drip of ∼3,000 units per day, leading to a diagnosis of type B insulin resistance. A1c on admission was 14%. After ∼5 days, she transitioned to U-500 that was titrated over 2 weeks to a total daily dose of 3,000 units with blood glucose between 98 and 177 mg/dL. She developed bilateral BP approximately 43 days from onset of DKA and 36 days after starting U-500 insulin with improved glycemic control. At last follow up 5 years later she still had residual facial weakness. Case 3: A 25 year-old Caucasian male with history of diabetes due to type A insulin resistance (Rabson-Mendenhall Syndrome) and recurrent ketosis on U500 insulin &amp;gt;1,000 units daily had poor adherence to insulin and diet with A1c of 14.3%. 3 weeks after A1c measurement he was started on a Continuous Glucose Monitor (CGM), leading to dramatic change in diet and medication adherence, with reduction in the estimated A1c based on glucose management indictor (GMI) to 7.7% within 3 weeks. 3 weeks after starting CGM use with improved compliance and glycemic control, he developed unilateral BP, which fully recovered after 1 month.We report 3 cases in which onset of BP was observed in rapid temporal correlation with massive increases in insulin dose and/or improvement in glycemia. Severe insulin resistance and rapid decrease of glycemic levels may lower intravascular volume and narrow vessels, leading to microvascular disruption of the vasa nervorum, ultimately causing mononeuropathy. A more gradual approach to glycemia management in patients with severe insulin resistance may be warranted to mitigate this risk. Presentation: Thursday, June 15, 2023