Resolution Of Ketoacidosis Research Articles

12621 Convergence Of Sglt2 Inhibitors And Glp1 Agonists: Unveiling The Recipe For Euglycemic Diabetic Ketoacidosis

Abstract Disclosure: U. Syed: None. N.E. Fretes Oviedo: None. V. Variar: None. Introduction: Euglycemic diabetic ketoacidosis (DKA) is a known adverse effect associated with the use of SGLT2 inhibitors. The concomitant initiation of GLP1 agonists with SGLT2 inhibitors presents a potential synergistic risk, precipitating metabolic acidosis without significant hyperglycemia. The individual propensity of both medication classes to contribute to metabolic disturbances highlights the necessity for heightened clinical awareness. Clinical Case: We present a case of a 34-year-old female with morbid obesity and Type 2 diabetes mellitus, receiving tirzepatide, metformin, and empagliflozin. The patient was initiated on empagliflozin 4 days prior, and tirzepatide one day prior to presentation. Shortly after commencing tirzepatide, she experienced symptoms of decreased appetite, abdominal pain, and vomiting. Workup was consistent with DKA with blood glucose < 250 mg/dL. Management involved strict adherence to DKA protocols. The patient’s symptoms resolved with resolution of ketoacidosis. Conclusion: Euglycemic DKA poses a diagnostic challenge for patients on SGLT2 inhibitors. Concurrent administration of GLP1 agonists, while not directly implicated, may exacerbate this condition, by their gastrointestinal side effects and resultant metabolic abnormalities. Awareness of potential interactions and associated risk factors is crucial for timely diagnosis and management. Presentation: 6/3/2024

The Effects of Subcutaneous Rapid-Acting Insulin Aspart in the Treatment of Mild and Moderate Diabetic Ketoacidosis in Children: A Prospective Study.

Background and objectives The traditional treatment approach to diabetic ketoacidosis (DKA) involves the replacement of fluid and electrolyte deficits and a continuous intravenous infusion of regular insulin. Several clinical trials supported the administration of subcutaneous rapid-acting insulin analogs in the management of uncomplicated DKA. This study aimed to determine the effects/safety of subcutaneous rapid-acting insulin aspart injections in treating uncomplicated mild and moderate DKA in children. Methods In this prospective study in 2022, 25 children with mild/or moderate DKA were enrolled. The main outcome measure was median time (hours) for the resolution of ketoacidosis. Data recorded were as follows: clinical characteristics, severity of ketoacidosis and dehydration, blood glucose, sodium, potassium, creatinine, urine ketones, hospitalization's duration, and complications. Based on the degree of dehydration, fluid deficit was replaced by sodium chloride 0.45%. Insulin aspart 0.15 units/kg subcutaneous injections were given every 2 hours in the hospital outside ICU. Blood glucose was measured hourly and blood gases every 2 hours. Ketoacidosis was considered resolved when the patient did not have nausea/vomiting, was conscious, and could eat, and blood glucose was <250 mg/dL, pH was >7.30, and/or HCO3 was >15 mmol/L. Results Of 25 DKA patients (mean age 11.06±3.89, range 4-17 years, 60% girls), 16 cases (64%) had established type 1 diabetes. Overall, 13 (52%) cases had mild ketoacidosis (average pH=7.25), and 12 (48%) cases had moderate ketoacidosis (average pH=7.15). The mean time to resolution of ketoacidosis was 11.24 hours. All but one patient met DKA recovery criteria without complications. Mild cases compared to moderate cases of DKA had a shorter duration to resolution of DKA (p = 0.04). Mean duration of hospitalization was 2.3 days. No electrolyte disturbances, hypoglycemia events, readmission or mortality, or other adverse effects were observed. Conclusion In children with mild and moderate DKA, subcutaneous rapid-acting insulin aspart administration was an effective, safe, and convenient treatment.

THU293 Enhancement Of Best Practices In Diabetic Ketoacidosis Management Using Standardized Order-sets vs Individual Practitioner Orders

Abstract Disclosure: C. Yim: None. Q. Li: None. T.G. Arnason: None. Diabetic ketoacidosis (DKA) is a hyperglycemic emergency occurring in diabetics due to insulin deficiency. This results in urinary losses of water and electrolytes (sodium, potassium, chloride) and ultimately extracellular fluid volume depletion. Hallmark features of DKA include ketoacidosis, arterial pH &amp;lt; 7.3, bicarbonate &amp;lt;15 mmol/L and an anion gap of &amp;gt;12 mmol/L. The 2018 Diabetes Canada (DC) guidelines outline the key steps of DKA management including fluid resuscitation, resolution of ketoacidosis, correction of electrolytes and management of precipitating factors. Its detailed algorithm identifies three pillars to DKA treatment: IV fluids, serum potassium and acidosis. A 2016 DKA outcome audit at the Royal University Hospital (RUH) in Saskatoon identified that practitioners diverged considerably from (2013) Canadian Diabetes Association guidelines. Subsequently, two standardized preprinted DKA order sets were developed incorporating the 2018 DC recommendations for i) INITIAL and ii) MAINTENANCE DKA management. Their rollout overlapped with annual academic half day sessions on DKA management for postgraduate year 1 residents in internal medicine. These order-sets were initially implemented at RUH in November 2018 and subsequently adopted by some practitioners at St. Paul’s Hospital (SPH). To ensure the order-sets were promoting improved outcomes and adhering to best practices, a retrospective chart review was conducted of all adult DKA admissions at RUH and SPH from Nov. 13, 2018 to December 31, 2020. In total, 279 hospital admissions were reviewed: 99 used practitioners’ own orders, 115 used both initial and maintenance order-sets, 26 used only the initial order-set and 38 used only the maintenance order-set. Use of the INITIAL order set significantly improved compliance (p &amp;lt; 0.0001) with DC 2018 guidelines for recommended insulin dose and timing, fluid resuscitation as well as potassium, sodium and dextrose replacement. Use of the MAINTENANCE order set consistently enhanced outcomes for intravenous fluid selection, subcutaneous insulin overlap, and ensuring a closed anion gap at transition (p &amp;lt; 0.0001). Additionally, the chart review revealed that there were hospital differences for uptake of order sets and compliance to DC 2018 guidelines. There was a significant uptake of order sets at RUH versus SPH (p &amp;lt; 0.0001). RUH consistently met outcomes for appropriate insulin dosing, potassium and dextrose replacement (p &amp;lt; 0.0001). RUH also consistently overlapped IV and SC insulin and ensured a closed insulin gap. The anion gap remained consistently closed post-transition at RUH versus SPH (p = 0.035). These results suggest that utilization of a DKA order set does significantly promote adherence to key best practices outlined in the DC 2018 guidelines. Presentation: Thursday, June 15, 2023

THU359 A Classical Case Of SGLT-2 Inhibitor Euglycemic Ketoacidosis In A Patient With Glucotoxicity

Abstract Disclosure: S. Amankwah: None. O.B. Olajide: None. Background: SGLT-2 inhibitors have been demonstrated to be beneficial in protecting comorbid cardiovascular or kidney disease while providing modest improvement in glycemia. However, they are not ideal for initial therapy for patients with very poorly controlled type 2 diabetes. This is a case where SGLT-2 inhibitor monotherapy led to diabetic ketoacidosis. Clinical Case: A 68-year-old woman with type 2 diabetes for 30 years, hypertension, hyperlipidemia, and depression presented to the hospital with complaints of headache, nausea, vomiting, dizziness, fatigue for the past three days. She had no fever, cough, shortness of breath or dysuria. She had not been taking any oral hypoglycemic agents for many months as she was trying to control her diabetes with lifestyle modifications. However, after the passing of her husband three months prior, she became less motivated in managing her health. Ten days prior to her hospitalization, the patient was newly prescribed empagliflozin 10 mg daily by her primary care provider due to uncontrolled hyperglycemia. She refused to resume metformin due to her history of gastrointestinal intolerance. She was previously on glipizide, but this was not restarted as she previously had poor glycemic control on it. On arrival at the ER, her temperature was 97.9 F, heart rate 112 bpm, respiratory rate 22 bpm, blood pressure 105/63 mmHg, and pulse oximetry on room air was 97%. Physical exam was unremarkable. Her serum glucose was 228 mg/dL, anion gap 15, pH 7.1, serum bicarbonate 15 mEq/L, serum acetone 3+, urine ketones greater than 150 mg/dL, serum creatinine 1.26 mg/dL and hemoglobin A1c was 13.2%. Her chest X-ray was unremarkable and COVID 19 test was negative. Euglycemic diabetic ketoacidosis (EDKA) was suspected secondary to the use of empagliflozin. This was discontinued and the patient was treated with intravenous insulin and fluids. Her serial blood tests showed resolution of ketoacidosis within 12 hours, and she was then transitioned to subcutaneous insulin. She was discharged home after 2 days of hospitalization on insulin therapy. Discussion: This case demonstrates the potential for SGLT-2 inhibitors to cause EDKA. It is important to acknowledge this complication can happen in cases where SGLT-2 inhibitors are used as monotherapy in diabetic patients with glucotoxicity. The mechanism of action of SGLT2 inhibitors is to enhance excretion and block reabsorption of filtered glucose from the proximal convoluted tubule. The resultant glycosuria creates a state of carbohydrate starvation and volume depletion, increasing the glucagon/insulin ratio, resulting in a state of severe dehydration and ketosis. Patients with glucotoxicity are at a higher risk to develop ketoacidosis as they have marked beta cell insufficiency. It is thus highly recommended to initially treat these patients with insulin rather than oral agents. Presentation: Thursday, June 15, 2023

Evaluation of Early Insulin Glargine Administration in the Treatment of Pediatric Diabetic Ketoacidosis.

In the management of diabetic ketoacidosis (DKA), the standard of care is to administer insulin glargine after ketoacidosis has resolved and the patient is transitioning from intravenous (IV) insulin to subcutaneous insulin; however, there is evidence to suggest that earlier administration of insulin glargine may accelerate resolution of ketoacidosis. The objective of this research is to determine the efficacy of early subcutaneous insulin glargine on time to resolution of ketoacidosis in children with moderate to severe DKA. This retrospective chart review evaluated children age 2 to 21 years old admitted for moderate to severe DKA who received insulin glargine within 6 hours of hospital admission (early insulin glargine) compared with those who received insulin glargine greater than 6 hours from admission (late insulin glargine). The primary outcome was duration of time the patient received IV insulin. A total of 190 patients were included. The median time on IV insulin was lower in patients who received early insulin glargine compared with those who received late insulin glargine (17.0 [IQR, 14-22.8] vs 22.9 hours [IQR, 4.3-29.3]; p = 0.0006). Resolution of DKA was faster in patients who received early insulin glargine compared with those who received late insulin glargine (median, 13.0 [IQR, 9.8-16.8] vs 18.2 hours [IQR, 12.5-27.6]; p = 0.005). Length of pediatric intensive care unit (PICU) and hospital stay and incidences of hypoglycemia and hypokalemia were similar between the 2 groups. Children with moderate to severe DKA who received early insulin glargine had a significantly lower time on IV insulin, as well as significantly faster time to resolution of DKA when compared with those who received late insulin glargine. There were no significant differences observed in hospital stay and rates of hypoglycemia and hypokalemia.

A case series of euglycemic starvation ketoacidosis in pregnant women with COVID-19 infection: atypical presentations

Background: We present a case series of euglycemic starvation ketoacidosis in pregnant women with coronavirus disease 2019 (COVID-19) infection. Our patients presented with fever and typical respiratory symptoms secondary to COVID-19 infection in the third trimester. It was complicated by severe metabolic ketoacidosis, likely contributed by the hypermetabolic state of pregnancy, maternal starvation, and increased metabolic demand due to COVID-19 infection. Case Presentation: Among most of the cases, there was a swift resolution of ketoacidosis, through timely fluid resuscitation, dextrose, and insulin. But despite those measures, most of the patients had to undergo emergency cesarean section due to maternal deterioration, preterm delivery, and fetal distress. All the mothers recovered well and were discharged home, but there was one case of neonatal death after preterm delivery. Conclusion: These cases illustrate the importance of early diagnosis of euglycemic ketoacidosis, prompt management, and close monitoring to obviate adverse materno-fetal outcomes in pregnant women with COVID-19 infection.

PSUN239 Severe Insulin Resistance and Hyperglycemia with Mild COVID-19 Infection

Abstract Introduction Covid-19 infection (CI) is known to cause hyperglycemia and insulin resistance in patients with and without diabetes. Prior reports have correlated the degree of hyperglycemia to the severity of the CI. However, not much data is available regarding severe insulin resistance in patients with mild CI who are otherwise asymptomatic and not on steroids. Case We report a 48-year old male with type-1 diabetes, asymptomatic CI and renal failure, on dialysis who was admitted with diabetic ketoacidosis (DKA). Patient had refused insulin and hemodialysis treatments for one week and was noted to be confused by staff in his long-term facility. Upon presentation, he was initiated on intravenous (IVIT) insulin infusion therapy and transitioned to subcutaneous (SQ) insulin the following morning. That evening, hyperglycemia worsened (&amp;gt;500 mg/dl), necessitating reinstatement of the IVIT. Hyperglycemia persisted (no excess carbohydrate intake reported by nursing) and IVIT was continued as attempts to change to SQ therapy were unsuccessful. He was dialyzed for two consecutive days after admission and then changed to alternate day schedule. On day 4, hyperglycemia worsened to &amp;gt;500 mg/dl persistently, IVIT rate was increased to 24 units/hr but blood sugars persisted in the &amp;gt;500 range. Work up for evaluating Covid-related inflammation and insulin resistance was sent. After 6 hours of IVIT at 24 U/hr, he was given a relatively higher dose of SQ-insulin (insulin glargine 20 units and insulin lispro 30 units SQ). IVIT rate was gradually tapered based on blood sugars and stopped 6 hours after SQ-insulin was given. Approximately eight hours after receiving SQ-insulin, he was noted to be hypoglycemic, and he received two amps of D-50. His blood sugar stabilized, and he continued to do well subsequently and was maintained on basal-bolus therapy. The on-call nurse confirmed good IV access for the IVIT access line. The IV insulin infusion fluid from bag was sent for analysis which showed that insulin was present in the infusion bag. Inflammatory markers showed high levels of cortisol, ferritin, growth hormone, C-reactive protein and sedimentation rate. Insulin antibodies were also present. D-dimer was normal, and fibrinogen was only mildly elevated. Conclusion This is a rare case of severe insulin resistance in a patient with mild Covid-19 infection and underlying type 1 diabetes, who developed severe insulin resistance with poor response to high doses IV insulin. He ultimately responded a combination of high dose subcutaneous insulin and high doses IV insulin infusion therapy with resolution of ketoacidosis and hyperglycemia. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Euglycemic DKA Associated With SGLT2 Inhibitors

Background: DKA associated with SGLT2 inhibitors also known as Euglycemic DKA (EDKA) is a rare condition characterized by milder degrees of hyperglycemia with a blood glucose level < 200 mg/dl. Unfortunately, this unusual feature can often lead to missed or delayed diagnosis with potential life-threatening outcomes. Clinical Case: The patient is a 53-year-old Caucasian male with PMH of type 2 diabetes mellitus treating with Metformin and Empagliflozin. He presented to the emergency room with shortness of breath, flu-like symptoms, and decreased oral intake for a couple of days. Vital signs at presentation were: Temperature 98.2 °F, pulse rate 108 beats/min, respiratory rate 28 breaths/min, and blood pressure 134/72 mmHg. He was alert but ill-looking, moderately dehydrated with dry mucus membranes. The rest of the physical examination was unremarkable at the time of admission. In the initial blood work, sugar was found to be mildly elevated (163mg/dl), and hemoconcentration besides mild pre-renal acute kidney injury was detected. He was also found infected by the COVID-19 virus without hypoxemia or signs of pneumonia. Arterial blood gases showed metabolic acidosis with an elevated anion gap (PH 7.21, CO2 39.93mmHg, HCO3− 10mEq/L, anion gap 21mEq/L). Urine analysis was positive for ketones and glucose. After ruling out other causes of metabolic acidosis by screening for alcohols, salicylates, acetaminophen, lactic acid, and urine toxicology; the diagnosis of EDKA was made. He was treated with a 3L bolus of IV normal saline and an insulin drip with dextrose solution started as per the protocol based on his glucose levels and promptly admitted to the intensive care unit (ICU). Serial blood tests showed gradual resolution of ketoacidosis and anion gap normalized after 36 hours when insulin drip was stopped and replaced by subcutaneous insulin therapy. Conclusion: SGLT2 inhibitors increase the urinary excretion rate of glucose and subsequent fall in plasma glucose level. Thus, In the absence of exogenous insulin use, increase glucagon release resulting in upregulation of lipolysis and activation of the ketogenesis. Factors such as low oral intake, concurrent infection, and alcohol use can also exacerbate the process. Timely diagnosis of EDKA can be a challenge for physicians unfamiliar with this class of medications, additionally, ketone studies and blood gas analyses are not part of the routine workup for diabetic patients in the emergency department. We recommend all first-line care providers to consider ketosis in ill patients with diabetes and metabolic acidosis, despite the normal or near-normal serum glucose levels. EDKA is mainly a diagnosis of exclusion, but treatment is not different from DKA; correcting dehydration by using intravenous fluids and then, initiating insulin drip along with dextrose-containing solutions, and frequent monitoring of serum anion gap.

Low-Dose (0.05 Unit/kg/hour) vs Standard-Dose (0.1 Unit/kg/hour) Insulin in the Management of Pediatric Diabetic Ketoacidosis: A Randomized Double-Blind Controlled Trial

To compare the efficacy of insulin infusion of 0.05 Unit/kg/hour vs 0.1 Unit/kg/hour in the management of pediatric diabetic ketoacidosis (DKA). Randomized, double-blind controlled clinical trial. Pediatric critical care division of a tertiary care hospital from October, 2014 to July, 2018. Children aged 12 years or younger with a diagnosis of DKA. Children with septic shock and those who had received insulin before enrollment were excluded. Low-dose (0.05 Unit/kg/hour) vs. Standard-dose (0.1 Unit/kg/hour) insulin infusion. The primary endpoint was time for resolution of DKA (pH ≥7.3, bicarbonate ≥15 mEq/L, beta-hydroxybutyrate <1 mmol/L). Secondary outcomes were the rate of fall in blood glucose until 250 mg/dL or less and the rate of complications (hypokalemia, hypoglycemia, and cerebral edema). Sixty patients were analyzed on an intention-to-treat basis (Low-dose group: n=30; Standard-dose group: n=30). Mean (SD) time taken for the resolution of ketoacidosis was similar in both groups [22 (12) vs 23 (18.5) hours; P=0.92]. The adjusted hazard ratio (95% CI) of the resolution of ketoacidosis was lower in the low-dose group [0.40 (0.19 to 0.85); P=0.017]. Mean (SD) rate of blood glucose decrease until 250 mg/dL or less reached [56 (41) vs 64 (65) mg/dL/hour; P=0.41] and time to achieve the target [4.2 (3.1) vs 4.8 (3.3) hours; P=0.44] were similar in both groups. Hypokalemia [30% vs 43.3%; P=0.28] and hypoglycemia [3.3% vs 13.3%; P=0.35] were lower in low-dose group. No child had cerebral edema, and no mortality occurred. Time for resolution of ketoacidosis was similar in the low-dose and standard-dose insulin with a lower rate of therapy-related complications in the low-dose group. Hence, low-dose insulin infusion can be a safer approach in the management of pediatric DKA.

Lactation Ketoacidosis: A Systematic Review of Case Reports.

Background and Objective: Lactation ketoacidosis is a rare cause of high anion gap metabolic acidosis affecting breastfeeding mothers. We aim to review and analyze all cases of lactation ketoacidosis reported. Materials and Methods: A systematic search of PubMed/MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL), identifying relevant case reports published from 1 January 1970 to 31 December 2019. We extracted the following data: the first author, country, year of publication, age of the mother, age of the child, weight/body mass index (BMI) of the mother, precipitating factors, presenting symptoms, biochemical results, treatment, breastfeeding, and time from presentation to the resolution of ketoacidosis. Results: Sixteen case reports and 1 case series reporting 18 cases of lactation ketoacidosis were found. Presenting symptoms were nausea (72%, 13/18), vomiting (67%, 12/18), malaise (56%, 10/18), abdominal pain (44%, 8/18), dyspnea (33%, 6/18), headache (22%, 4/18), and palpitation (11%, 2/18). Dieting and physical exercise to lose weight were reported in 76% (14/18). The treatments included IV dextrose, sodium bicarbonate, insulin, rehydration, monitoring and replacement of electrolytes, and resumption of a balanced diet. The prognoses were good, with no mortalities. Conclusions: lactation ketoacidosis should be suspected in unwell breastfeeding women with high anion gap metabolic acidosis, after excluding other causes.

SUN-176 Euglycemic Diabetic Ketoacidosis withSGLT2 Inhibitor Presenting as Chest Pain in a Patient with Coronary Artery Disease on a Ketogenic Diet

Background: Euglycemic diabetic ketoacidosis (DKA) is a known complication of sodium-glucose cotransporter 2 (SGLT2) inhibitors. We report an unusual case of euglycemic DKA caused by an SGLT2 inhibitor during self-introduction of a ketogenic diet; initial concern was for acute coronary syndrome. Clinical Case: A 61-year-old man with a history of type 2 diabetes with a hemoglobin A1c of 8.3%, coronary artery disease, hypertension, and hyperlipidemia presented to the emergency room with nausea and chest pain. The patient had a 30-year history of diabetes and was on oral therapy for years before starting insulin with an average daily dosage of 28 units. Three years ago, he started an SGLT2 inhibitor, improved his lifestyle and glycemic control, and was able to stop insulin. His home medications included empagliflozin 10 mg daily, metformin 500 mg twice a day, liraglutide 1.8 mg subcutaneously daily, rosuvastatin 5 mg daily, ezetimibe 10 mg daily, and omeprazole 40 mg daily. He reported several weeks of atypical chest pain and computed tomography angiography showed total occlusion of the mid-right coronary artery. He underwent an exercise stress test that showed echocardiographic changes that were positive for ischemia and subsequently was scheduled to undergo a left heart catheterization in 1 week. In the interim, he was highly motivated to change his lifestyle. He adopted a ketogenic diet, significantly limiting his daily carbohydrate. Five days later, he developed persistent and increased right-sided chest pain along with nausea, and presented to the emergency room. On review of systems, he reported hunger and his wife reported an odd breath odor. His vitals were stable. His troponin was negative and EKG showed inferior Q waves similar to prior EKGs. Given concern for acute coronary syndrome, he underwent cardiac catheterization, which showed the known complete total occlusion of RCA with collaterals, for which intervention was not performed. Review of additional labs showed: glucose 110 [70-100 mg/dL], bicarbonate 17 [22-29 mmol/L], anion gap 17 [6-14 mmol/L], betahydroxybutyric acid 4.1 [<0.3 mmol/L], large quantity of urinary ketones and glucose. He was diagnosed with euglycemic DKA and treated with insulin, fluids, and dextrose with resolution of ketoacidosis and chest pain. Conclusion: The use of SGLT2 inhibitors is increasingly favored in those with established cardiovascular disease, and carbohydrate-restrictive diets are a popular form of nutritional therapy. This case highlights severe carbohydrate restriction as an important risk factor that may predispose patients on SGLT2 inhibitors to euglycemic DKA that demonstrated with an unusual presentation of chest pain.

SAT-470 A Case of Acromegaly with Concomitant Hypercortisolism Presenting with Diabetic Ketoacidosis

Background: Acromegaly is a rare disorder with an annual incidence of 4-6 new cases per 1 million population.1 Impairment in glucose metabolism has been previously described in such disorder, but diabetic ketoacidosis is rare. Case: A 25 year old, male, presented at our emergency room with seizures. Laboratory data showed hyperglycemia (blood glucose 418 mg/dl), ketonuria (urine ketone +2), and pure high anion gap metabolic acidosis consistent with severe Diabetic Ketoacidosis. Hba1c was 12%. A normal fasting C-peptide 1.68 ng/ml (1.10-4.40 ng/ml) indicate residual insulin secretion, or maybe an inappropriately normal response in the presence of severe hyperglycaemia hyperglycemia. Features of acromegaly were noted and hormonal evaluation showed elevated IGF-1 level at 484.50 ng/ml (83-344 ng/ml), supporting the diagnosis. Random growth hormone was elevated at 5.7 ng/ml (<3 ng/ml). GH suppression testing with oral glucose load was not done due to unstable glucose levels. An elevated 24 hour urine cortisol 6208.0 nmol (100.0-379.0 nmol/24h) may be associated with uncontrolled diabetes, or an underlying subclinical Cushing’s disease contributing to further insulin resistance. Other hormones of the anterior pituitary reveal normal thyroid function, central hypogonadism and hyperprolactinemia at 828.50 uIU/ml (58.0-475.0 uIU/ml) likely due to hypophyseal stalk compression by the tumor. Cranial MRI with contrast showed an enhancing sellar mass measuring 23.7 x 22.3 x 18.0 mm (AP x T x CC) which extends inferiorly to the upper portion of the prepontine cistern. Resolution of ketoacidosis required 360 units of regular insulin per day, without achieving target blood glucose levels. Blood glucose level was successfully controlled with insulin and oral hypoglycemic agents. There was incomplete resection of the mass following transphenoidal surgery. Conclusion: This case highlights the concomitant presence of increased counter regulatory hormones (GH and cortisol) and IGF-l levels in Acromegaly leading to increased insulin resistance, which are uncommon, but important causes of Diabetic Ketoacidosis. Reference: Melmed, S. (2016). Williams textbook of endocrinology. Elsevier Health Sciences.

Risk factors associated with resolution of diabetic ketoacidosis in pediatric critical care units

Objective: Diabetic ketoacidosis (DKA) is the main cause of morbidity and mortality in children with type-I Diabetes Mellitus. The goals of therapy are to correct dehydration, resolution of acidosis and fading of ketosis. Such serious complications necessitate closed monitoring of DKA patients with delicate, balanced therapy, probably at an intensive care facility. Regarding the fact that, each facility shoul determine the clinical profile of their own patient population, we aimed to investigate the risk factors for consequences and determine the timing of DKA resolution by analyzing the demographic and epidemiologic data, clinical outcome and the prognosis of diabetic ketoacidotic children admitted to PICU. Method: This descriptive, retrospective study was conducted in 105 children admitted to PICU with the complaints of DKA between January 2014 and December 2108. Demograhic data including age, gender, weight, height, body mass index (BMI), initial compliants with clinical findings and level of consciousness were recorded. Children were categorized into two groups depending on the timing of DM diagnosis (new onset of diabetes and established diabetes mellitus). DKA severity was determined by the degree of metabolic acidosis (mild, moderate, severe). SPSS-23 was used for statictics. Descriptive analyses were expressed as percentages, mean±standart deviation (SD), median with minimum and maximum values. Chi square and Fischer exact test were used for comparison of categorical variables. Student’s t-test, Mann Whitney U test and Wilcoxon rank sum test were assessed for continous variables. Pearson correlation coefficient and logistic regressions were used for correlations and to determine the risk factors. P-value < 0.05 was considered significant. Results: The patient demographics presented the mean age as 11.31±4.18 years, female/male ratio 1/1.4 and body mass index 18.48±4.48. Children were classified as mild DKA (29.5%), moderate DKA (35.2%) and severe DKA (35.2%) based on the acidosis severity. 48.6% of the patients had Kusmaull respiration; 30.5% had manifested altered consciousness. One patient had tomography-proven brain edema and had required mechanical ventilation due to neurological incapability to sustain airway Children with new onset of diabetes accounted for 51.4% of the study population. The mean age was 9.70±4.47 years; this group constituted a younger population compared the established DM patients (p<0.001). Altered mental state and kusmaull respiration also occurred at a higher rate and the major complaint seemed ae weight loss within two weeks (p=0.006, p=0.002, p<0.001 respectively). Children with established diabetes mellitus presented significant biochemical abnormalities in terms of elevated BUN and serum potassium levels (p<0.001, p<0.001); infections occurred as the major triggering factor for DKA at a rate of 80.4% at this group. We observed a positive correlation with DKA resolution with serum creatinine, calculated osmolality, anion gap (r=0.242, r=0.215, r=0.302) and a negative correlation with blood gas pH and HCO3 (r= -0.704, r= -0.694). In the multivariable regression model including age, gender, body mass index, PRISM-3 score, BUN, serum potassium, phosphate and chloride, only blood gas pH and new onset of diabetes appeared to be the independent risk factors for DKA resolution. 0.1 unit decrement in blood gas pH elongated the resolution by 3.76 hours (p<0.001, adjusted ratio: 0.743). New onset of diabetes mellitus also increased the length of resolution by 5.30 hours (p<0.001). Conclusions: Inıtial blood gas pH and presence of new onset of diabetes are the major risk factors in resolution of ketoacidosis.

Resolution of ketoacidosis in children with new onset diabetes: Evaluation of various definitions

AimsData are sparse concerning use of serum electrolyte parameters as compared to venous blood gas (VBG) measurements to monitor acid-base status during treatment of diabetic ketoacidosis (DKA). We explored the utility of various parameters to define DKA resolution by investigating the relationship of venous pH (vpH), anion gap (AG), serum bicarbonate (HCO3), and glucose concentration during management of DKA in children with new onset diabetes mellitus (NODM). MethodsWe included all patients with NODM presenting with DKA to Boston Children’s Hospital from 10/1/07–7/1/13. DKA was defined as serum glucose ≥ 200 mg/dL (11.1 mmol/L) and vpH<7.30; severity as mild <7.30, moderate<7.20, severe<7.10; resolution of DKA as vpH≥7.30 and AG≤18 mmol/L. We used Cox regression to determine time to DKA resolution, and logistic regression to evaluate different serum HCO3 cut-off values as predictors of DKA resolution. Results263 patients (133F, mean age 9.9±4.4 years, 74% White) were included. DKA was mild in 134 (51%), moderate in 75 (28%) and severe in 54 (20%). In mild DKA, AG closed after normalization of vpH; in moderate and severe DKA, AG closed before normalization of vpH. HCO3>15mmol/L correlated with vpH≥7.30, and had 76% sensitivity and 85% specificity to predict DKA resolution. Median times to DKA resolution were similar using two different definitions: vpH and AG (8.4h [IQR 6.3–11.9]) vs. HCO3>15 mmol/L (7.9 h [IQR 5.0–11.8]), p=.42. ConclusionsDuring management of pediatric DKA, HCO3 > 15 mmol/L reliably predicts resolution of DKA. In low-resource settings where VBG is unavailable, electrolyte parameters alone may be used to determine DKA resolution.

Everolimus-Induced Hypertriglyceridemia Manifesting as Acute Pancreatitis

Everolimus is used in the treatment of many advanced cancers like renal and breast cancer. Hypertriglyceridemia (HTG) is a known adverse effect of the drug. However, acute pancreatitis (AP) is not commonly reported. A 46-year-old Hispanic female with recurrent breast cancer had been treated with Everolimus (10 mg/day) for 6 weeks, who then developed elevated triglycerides (TG) and the Everolimus was stopped. Three days later, she presented to the emergency center with nausea and severe, mid-epigastric pain radiating to her back. Lab values included: sodium 127 mEq/L, lipase 795 U/L, blood glucose > 700 mg/dl, with normal calcium. The serum was milky in appearance, with TG > 1590 mg/dL. There was no history of diabetes or alcohol use. She was diagnosed with diabetic ketoacidosis (DKA) and admitted to the medical ICU for intravenous fluids, insulin drip and pain control. Despite resolution of ketoacidosis, her pain worsened and she remained anorexic. Gastroenterology was consulted and diagnosed her with AP due to HTG. After several days, her TG decreased to 336 mg/dL with above treatment, coinciding with improvement of her symptoms (Figure 1). Her diet was advanced and she was discharged with fenofibrates. TG level four months later normalized. Everolimus treatment was not re-attempted. Hypertriglyceridemia and drugs are common causes of AP. There are two main causes of HTG-induced AP (HTG-AP): primary (usually genetic or idiopathic) and secondary. The pathogenesis of HTG associated with mTOR inhibitors is unclear, but may be related to slow degradation of apolipoprotein B100 leading to dyslipidemia. Hyperlipidemia is thought to cause AP when the pancreatic lipase hydrolyzes the excess TGs circulating in the serum damaging the free fatty acids which in turn accumulate in the pancreas leading to severe inflammation of the pancreas. HTG also leads to impaired clearance of chylomicrons leading to pancreatic capillary hyperviscosity causing ischemia. HTG-induced AP may be clinically evident when TG levels exceed 1000 mg/dL. Treatment involves IV insulin, IV heparin, or plasmapheresis (in absence of hyperglycemia) with fenofibrates for long term management. Our patient likely had secondary HTG due to Everolimus. Awareness of Everolimus causing HTG-AP is important for gastroenterologists, especially those who may treat cancer patients.Figure: Timeline showing introduction of Everolimus and development of Hypertriglyceridemia.

Outcomes of Early vs Late Oral Nutrition in Patients With Diabetic Ketoacidosis Admitted to a Single Academic Institution Medical ICU

SESSION TITLE: Improving Outcomes in the ICU SESSION TYPE: Original Investigation Slide PRESENTED ON: Wednesday, November 1, 2017 at 02:45 PM - 04:15 PM PURPOSE: Diabetic ketoacidosis (DKA) is a potentially dangerous complication of diabetes often necessitating admission to the intensive care unit (MICU). It is associated with severe insulin deficiency, electrolyte abnormalities, and dehydration requiring insulin infusion and close electrolyte and blood glucose monitoring. Upon resolution of DKA, patients are gradually transitioned to subcutaneous insulin and oral nutrition. However, there is no recommendation on timing of oral nutrition. Potential disadvantages of early oral intake include fueling lipolysis and promoting ketogenesis, difficulty in blood sugar control, and development of ileus, all of which can lead to deterioration and longer ICU stay. Due to these concerns and lack of definitive recommendations, many institutional protocols prefer initial NPO status and often associate initiation of oral nutrition with resolution of DKA. Our study is aimed to investigate safety of oral nutrition prior to resolution of DKA in adult patients admitted to MICU. METHODS: Retrospective observational study was conducted at a single academic medical center. Time to DKA resolution was defined by the presence of both: 1) Glucose < 200 and 2) two of the three: pH ≥ 7.3, serum bicarbonate ≥15, and anion gap ≤12. Descriptive statistics and bivariate analysis was used to analyze patients' age, gender, race, Apache IV length of stay and mortality indices as well as the outcomes which included 28- and 90-day mortality, hospital and ICU length of stays and time to resolution of DKA. RESULTS: Between 12/2015 and 01/2017 there were 330 admissions to Scott and White Medical Center MICU with diagnosis of DKA. After excluding repeated hospitalizations of the same patients for DKA the final sample consisted of 146 unique patient admissions. Of those, 78 patients received oral nutrition prior to and 68 received oral nutrition after the resolution of DKA. No statistically significant difference was found between groups in age, gender, APACHE IV length of stay or APACHE IV mortality scores. There was a significant difference in race distribution, although proportions of caucasian and african-american patients comprising most of the study population were similar (23% vs 26% and 64% vs 69% in early vs late nutrition group respectively). Comparing the mortality of patients receiving early vs late oral nutrition no statistically significant difference was found: 5 patients died in the first 28 days (2 vs 3, p=0.68) and 6 died within 90 days (2 vs 4, p=1.0). Groups did not significantly differ in their mean hospital length of stay (5.6 vs 7.1 days in early vs late group respectively, p=0.3) but there was statistically significant difference in the mean ICU length of stay (2.4 vs 3.6 days, p=0.044) and the mean time to DKA resolution (53.8 vs 133.1 hours, p<0.0001). CONCLUSIONS: Oral nutrition in patients admitted to MICU for DKA initiated prior to the resolution of ketoacidosis appears safe and could potentially decrease the time to resolution of DKA and ICU length of stay. CLINICAL IMPLICATIONS: A larger prospective study can be conducted randomizing patients in early vs late oral nutrition groups seeking to replicate our findings and further analyze the impact of oral nutrition in this complex physiologic condition. DISCLOSURE: The following authors have nothing to disclose: Kirill Lipatov, Susan Seago, Kevin Kurian, Jonathan Walsh, Mason Sanders, Molly Clark, Jason Ettlinger, Megan Newman No Product/Research Disclosure Information

A reaudit of the management of diabetic ketoacidosis after the introduction of a local protocol based on the JBDS guidelines: then and now

Background: In 2010 the Joint British Diabetes Societies Inpatient Care Group issued guidelines for the management of Diabetic Ketoacidosis. A new management guideline and bedside chart based on these guidelines were introduced in our Health Board in 2012. Methods: A retrospective re-audit of 33 patients managed according to the new guideline, admitted from October 2013 to October 2014. Results were compared to 2010 prior to implementation of the guideline and the first audit cycle September 2012 to 2013 immediately after. Results: 3 admissions a month. Median age was 34 years, 94% admitted with established DKA and vomiting (70%), as the commonest presenting symptom. Length of stay: median of 2 days, with mortality of 0%. Median time to IV fluids: 35 (2 – 420) minutes, time to fixed rate intravenous insulin infusion: 40 (2 to 210) minutes. Long acting insulin continued in 94% with 21% hypoglycaemia (n=7) and 6% hypo-kalaemia rates (n=2). Median time to resolution of ketosis: 12 hours. Variable rate insulin started in 55% post DKA protocol, due to ongoing nausea and vomiting.100% of patients were reviewed by the inpatient diabetes care team. Conclusions: Sustained improvements in median times to insulin, fluids and >50% reduction in hypoglycaemia. Reduced time on intravenous insulin compared to pre guideline in 2010 with an objective end point for resolution of ketoacidosis. Bedside potassium monitoring remains suboptimal.

Relative hypoaldosteronism in a patient with Wolcott‐Rallison syndrome

Wolcott-Rallison syndrome is an autosomal recessive, multisystem disorder with onset of diabetes in the neonatal period or early infancy. A 9-year-old girl with diabetes and growth failure from 2 months of age presented with ketoacidosis and multiple organ failure. Evaluation for short stature revealed epiphyseal dysplasia. A homozygous mutation in the EIF2AK3 gene confirmed the clinical diagnosis of Wolcott-Rallison syndrome. She was euthyroid. Biochemical evaluation for potential adrenal dysfunction because of persistently elevated serum potassium (range 5.9-6.3 meq/l) and low serum sodium levels (range 128-130 meq/l) 2 weeks after resolution of ketoacidosis yielded normal findings with respect to basal corticotropin (31 pg/ml) and cortisol (18.7 μg/dl) levels. Estimated GFR-Schwartz (36.9 ml/min/1.73 m(2) ) was consistent with stage 3 chronic renal failure. The transtubular potassium gradient was 1.39 (normal value in hyperkalemic states: > 4.1). The plasma aldosterone (upright: 241.3 pmol/l) was within normal ranges, and plasma renin [39 pg/ml (range 5.41-34.53 pg/ml)] was slightly elevated. The patient was diagnosed as having relative hypoaldosteronism and was started on a sodium-rich diet and low potassium. Failure to respond to the dietary intervention prompted a trial of oral fludrocortisone with subsequent normalization of electrolyte levels. This is the first case report of Wolcott-Rallison syndrome complicated with relative hypoaldosteronism. Further research is needed to probe the causal inference of relative hypoaldosteronism with chronic renal failure in patients with Wolcott-Rallison syndrome.

The Utility of Continuous Subcutaneous Insulin Infusion for Management of Mild to Moderate Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is the commonest hyperglycemic emergency in people with diabetes. Fluid and insulin, commonly via intravenous route, is the mainstay of treatment; however, other methods of insulin administration have been tried. In this study, we aimed at comparing the efficacy and safety of continuous subcutaneous insulin infusion (CSII) to intravenous (IV) insulin infusion protocol using a short acting insulin analogue, glulisine, in patients with mild to moderate DKA. This is a prospective randomized controlled trial including 30 patients with DKA randomly assigned to receive Glulisine insulin via CSII or IV infusion. Metabolic parameters were observed till resolution of DKA. Primary end point was assessment of the duration till resolution. Secondary end points included total length of hospitalization, amount of insulin used and the number of hypoglycemic events. There were no statistical differences in the mean duration of treatment until correction of DKA being 16.58 ± 3.68 hours for CSII group versus 14.60 ± 3.2 hours in the IV group, p=0.136. There was no mortality and no differences in the length of hospital stay, or the number of hypoglycemic events among treatment groups. However, the total amount of insulin administration until resolution of ketoacidosis was significantly higher, 61.50 ± 13.89 units, in CSII group compared to 46.60 ± 13.53 units in the IV group, p=0.009. We concluded that the use of CSII of glulisine insulin represented a safe and effective alternative to the use of IV glulisine in the management of patients with mild to moderate DKA.

The use of Aglepristone in the treatment of pregnancy related diabetic ketoacidosis: description of a case in a bitch

Gestational diabetes mellitus (GDM) is a rare disease in dogs that depends from an endogenous insulin supply that is insufficient to meet the tissues demands for the action of diabetogenic molecules like progesterone (P4), estradiol, growth hormone (GH), placental lactogen and placental cytokines. This report describes for the first time a case of GDM complicated by ketoacidosis treated with the P4 receptor blocker aglepristone. In our case aglepristone seemed to increase insulin sensitivity, helping in the resolution of ketoacidosis and of diabetes mellitus. Aglepristone may represent an effective and well tolerated therapeutic option in case of GDM.