Diabetic Ketoacidosis Patients Research Articles

Impact of Hypophosphatemia and Hypomagnesaemia on Diabetic Ketoacidosis patient's Outcome in Medical Intensive Care Unit

Background: Diabetic ketoacidosis (DKA) is a life-threatening condition of biochemical derangements comprising hyperglycemia, acidosis, and ketonemia. The study aimed to explore the prognostic impact of phosphate (Po4) and magnesium (Mg) levels on DKA-associated morbidity and mortality.Methods: Sixty-eight patients with DKA were admitted to the intensive care unit (ICU) in the Internal medicine Department in Zagazig University Hospital over the period of 6 months were evaluated serially for Po4 and Mg levels among other routine investigation. The patients were followed for the in-hospital clinical outcome.Results: hyponatremia, HbA1c, random blood sugar (RBS), creatinine, urea, ICU stay, low pH, and hypophosphatemia showed a strong correlation with a mortality rate (P

1123-P: Analysis of Readmissions for Diabetic Ketoacidosis in Patients with Hidradenitis Suppurativa: A Nationwide Analysis

Hidradenitis suppurativa (HS) is known to increase the risk of diabetes mellitus. This study aims to compare rates and outcomes of 30-day readmissions following admissions for type 1 diabetic ketoacidosis (T1DKA) in patients with and without co-existing Hidradenitis Suppurative (HS) in the United States. We analyzed the 2018 National Readmission Database. We included index hospitalizations for all patients (aged≥18 years) with a principal diagnosis of T1DKA using ICD-10 codes. We further sub-stratified this group into those with and with a secondary diagnosis of HS. Chi-square tests and regression analysis were used to compare rates and outcomes of 30-day readmissions between both groups. We excluded elective and traumatic readmissions. A total of 94,461 index hospitalizations for T1DKA, that were discharged alive, were included in the analysis. 109 (0.2%) of these, had co-existing HS. A total of 15,614 (16.5%) readmissions occurred within 30 days. Readmission rates were similar between HS and non-HS group (21.8% vs. 16.5%, p=0.328). HS group had a similar mean hospital length of stay (3.0 days vs. 2.9 days, p=0.645) and mean total hospital costs ($6,878 vs. $7,236, p=0.691) compared to the non-HS group. Readmissions for T1DKA in HS patients were associated with a total of 331 hospital days and $747,976 in hospital costs. T1DKA without coma was the most common reason for readmission in both groups. HS patients admitted for T1DKA have a greater, but statistically non-significant rate of 30-day readmission, and similar readmission outcomes compared to non-HS patients admitted for TIDKA. Disclosure E. Edigin: None. H. Shaka: None. P. O. Eseaton: None. M. Almani: None. A. Kichloo: None. P. E. Ojemolon: None. D. Jakhar: None.

1050-P: Rates, Characteristics, and Comparison of Readmissions for Diabetic Ketoacidosis in Patients with Psoriasis in the United States: A National Population-Based Study

Introduction: Psoriasis is known to increase the risk of type 1 diabetes mellites. This study aims to compare rates and outcomes of 30-day readmissions following admissions for type 1 diabetic ketoacidosis (T1DKA) in patients with and without psoriasis in the United States. Methods: We analyzed the 2018 National Readmission Database. We included index hospitalizations for all patients (aged≥18 years) with a principal diagnosis of T1DKA using ICD-10 codes. We further sub-stratified this group into those with and with a secondary diagnosis of psoriasis. Chi-square tests and regression analysis were used to compare 30-day readmission rates and readmission outcomes between both groups. We excluded elective and traumatic readmissions. Results: A total of 94,461 index hospitalizations for T1DKA, that were discharged alive, were included in the analysis. 357 (0.4%) of these, had co-existing psoriasis. 15,614 (16.5%) readmissions occurred within 30 days. Readmission rates were similar between psoriasis and non-psoriasis group (15.0% vs. 16.5%, p=0.663). The psoriasis group had a similar mean hospital length of stay (3.3 days vs. 2.9 days, p=0.077) and total hospital costs ($8,435 vs. $7,231, p=0.055) compared to the non-psoriasis group. Readmissions for T1DKA in psoriasis patients was associated with a total of 1,191 hospital days and $3,014,844 in-hospital costs. T1DKA without coma was the most common reason for readmission in both groups. Conclusion: Psoriasis patients admitted for T1DM have similar 30-day readmission rates and readmission outcomes compared to non-psoriasis patients admitted for TIDM. Disclosure E. Edigin: None. P. E. Ojemolon: None. H. Shaka: None. P. O. Eseaton: None. M. Almani: None. D. Jakhar: None. I. R. Asemota: None. E. Akuna: None.

Outcomes of diabetic ketoacidosis in a tertiary centre with restricted intensive care unit bed capacity.

Diabetic ketoacidosis (DKA) is an acute metabolic condition, sometimes requiring admission to an intensive care unit (ICU). To investigate the outcomes of DKA patients admitted to a hospital with restricted ICU capacity. We included all DKA patients above age 18 who were admitted to a tertiary hospital during 2004-2017. We conducted multivariate logistic regression analysis adjusted for ICU bed availability to analyse parameters associated with ICU admission, and a composite outcome of mortality, DKA recurrence and mechanical ventilation. Among 382 DKA patients in our cohort, 94 (24.6%) were admitted to the ICU. The in-hospital mortality was 4.7%. Low bicarbonate (<10 mmoL/L) and pH (<7) levels at presentation were associated with ICU admission (P < 0.001 for both). In multivariate models availability of beds in the ICU was not associated with ICU admission, mortality or DKA recurrence of any type. In a setting of limited ICU capacity, DKA treatment does not necessarily require admission to the ICU. When the rising rates of diabetes mellitus and the associated elevated rates of DKA are taken into account, our results highlight the importance of including step-down units when devising local protocols for care of these patients.

1019-P: Outcomes of Hospitalized DKA Patients with Hypocalcemia: An Analysis of National Inpatient Sample

Background: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM), associated with significant mortality. Patients frequently develop a constellation of electrolyte disturbances, including hypocalcemia. We wanted to analyze the in-hospital outcomes of DKA patients with hypocalcemia. Methods: We conducted a retrospective observational study using the National Inpatient Sample (NIS) from 2017 and 2018. Patients with type 1 and 2 DM with a principal diagnosis of DKA were selected and stratified based on the presence of hypocalcemia. The primary outcome was in-hospital mortality. The secondary outcomes included the development of sepsis, acute kidney injury (AKI), Acute respiratory failure(ARF), cerebral edema (CE), length of stay (LOS), and total charges. Confounders were adjusted for using multivariate regression analysis. We included AKI and Sepsis in the multivariate analysis for mortality since hypocalcemia can be seen in both conditions. Results: Out of 379,614 DKA admissions during the study period, 6894(1.8%) had hypocalcemia. When adjusted to patient characteristics, co-morbidities and hospital characteristics, those with hypocalcemia had higher odds of AKI (aOR=1.28, CI=1.13-1.45, p=&amp;lt;0.001), sepsis (aOR=2.88, CI=2.07-4.01, p=&amp;lt;0.001), ARF (aOR=3.23, CI=2.59-4.03, p=&amp;lt;0.001) and CE (aOR=2.51, CI=1.24-5.12, p=0.011) compared to those with only DKA. When adjusted to the occurrence of AKI and sepsis, patients with hypocalcemia and DKA had higher odds of in-hospital mortality (aOR= 2.61, CI=1.47-4.64, p=0.001), longer LOS (+1.01 day, CI 0.79-1.24, p&amp;lt;0.001) and higher total hospital charges (+$14,649, CI $11,442-17,855, p&amp;lt;0.001). Conclusion: Hypocalcemia is associated with increased odds of mortality in patients admitted with DKA and it could be used as a disease severity marker. Further studies need to be done to determine if hypocalcemia in DKA is merely a predictive factor or a direct contributor to increased mortality. Disclosure M. Murthi: None. C. D. Corpuz: None. S. Velagapudi: None. M. Ramirez: None. R. Atluri: None. H. Shaka: None.

1278-PUB: Acid-Base Alterations after Isotonic Fluid Resuscitation of Patients in Suspected DKA in the Pediatric Emergency Department

Introduction: Pediatric patients presenting to the emergency department (ED) for diabetic ketoacidosis (DKA) often present with dehydration, with admission to the intensive care unit (ICU) dependent on measures of dehydration and acidosis. Objective: The objective of this study was to assess the effect of fluid resuscitation in the ED on patient disposition to the ICU or floor based on changes in markers of dehydration and acidosis. Methods: This investigation was a single-center, retrospective study of patients 6 to 18 years old presenting to the ED for concern of DKA from 2016-2019. Patients with pre-bolus and post-bolus venous blood gas (VBG) were included. Each pre-bolus and post-bolus VBG was classified as meeting ICU or floor criteria. Based on the protocol developed at Rainbow Babies and Children’s Hospital, ICU criteria were pH &amp;lt; 7.3 and/or bicarbonate (HCO3) &amp;lt; 15 (on VBG or renal function panel). Dehydration was assessed using heart rate and blood urea nitrogen (BUN), adjusted by age. Continuous variables were analyzed using Kruskal-Wallis test, and categorical variables were analyzed with the chi-square test or Fisher’s exact test. Results: In this study, 187 patients met inclusion criteria. Post-bolus pH was increased in 52%, decreased in 41%, and unchanged in 7%. Post-bolus bicarbonate was increased in 44%, decreased in 53%, and unchanged in 2%. Of 145 patients with initial disposition to the ICU, 26 (17.9%) met floor criteria post-bolus, and no marker for dehydration distinguished this cohort (p=0.054 for heart rate, p=0.93 for BUN). Of 40 patients with initial disposition to the floor, 7 (17.5%) met ICU criteria post-bolus, and no marker for dehydration distinguished this cohort (p=0.68 for heart rate and p=1 for BUN). Conclusion: Patients presenting to the ED in DKA may have a decrease in pH or HCO3 following a normal saline bolus. In patients initially meeting criteria for the floor, up to 17.5% may change disposition to the ICU after a normal saline bolus. Disclosure S. Gera: None. S. P. Sheth: None. K. A. Kutney: None. S. Malay: None.

Diabetic Ketoacidosis and Dysregulation of Proglucagon Family of Molecules

ObjectivesAn increasing body of evidence supports a significant contributory role for pancreatic α-cell dysfunction in the pathophysiology of diabetic ketoacidosis (DKA). In normal physiology, high glucose levels stimulate insulin and inhibit glucagon secretion, while low glucose stimulates glucagon but inhibits insulin release. This regulatory mechanism is progressively lost in diabetes mellitus (DM), where diminished insulin levels are accompanied by hyperglucagonemia leading to the further aggravation of hyperglycemia caused by insulin deficiency. Glucagon is produced via the posttranslational modification of proglucagon in a process that also produces other proglucagon molecules including major proglucagon fragment (MPGF) and glucagon like peptide-1 (GLP-1). Here we hypothesized that DKA is associated with α-cell dysfunction leading to elevated levels of proglucagon molecules. MethodsWe measured levels of glucagon, GLP-1 and MPGF as indices of glucagon synthesis/α-cell function in the plasma of patients with DKA and in healthy controls. The inclusion criteria for DKA patients were glucose > 250 mg/dL, pH < 7.2, bicarbonate < 15mEq/L, presence of ketones and patients were part of a larger randomized trial. Samples were obtained at baseline prior to trial interventions. An independent sample t-test was used to compare differences. ResultsWe analyzed samples of 25 healthy controls and 59 individuals with DKA (47 T1DM and 12 T2DM) and found significant increase in glucagon levels in all of the DKA groups (controls 47 pg/mL (36, 67), T1DM 63 (40,135), T2DM 84 (61,105), p = 0.013). The differences were significant in MPGF too (controls 0.5 ng/mL (0.4, 0.8), T1DM 1.1 (0.7, 1.9), T2DM 1.3 (0.9, 2.0), p < 0.001), while differences in GLP-1 between groups did not reach statistical significance. C-peptide levels were significantly diminished in DKA and the levels of glucagon and C-peptide were strongly associated in healthy controls but not in DKA. ConclusionsOur data indicate that proglucagon family molecules may be actively contributing to the pathogenesis of DKA and may represent a potential site for future therapeutic interventions. Funding SourcesThe parental study of “Thiamine as adjunctive therapy for diabetic ketoacidosis” was supported through a grant from the National Institute of Health.

Early prediction models for prognosis of diabetic ketoacidosis in the emergency department: A protocol for systematic review and meta-analysis.

Background:Diabetic ketoacidosis (DKA) is one of the most serious complications after diabetes poor control, which seriously threatens human life, health, and safety. DKA can rapidly develop within hours or days leading to death. Early evaluation of the prognosis of DKA patients and timely and effective intervention are very important to improve the prognosis of patients. The combination of several variables or characteristics is used to predict the poor prognosis of DKA, which can allocate resources reasonably, which is beneficial to the early classification intervention and clinical treatment of the patients.Methods:For the acquisition of required data of eligible prospective/retrospective cohort study or randomized controlled trials (RCTs), we will search for publications from PubMed, Web of science, EMBASE, Cochrane Library, Google scholar, China national knowledge infrastructure (CNKI), Wanfang and China Science and Technology Journal Database (VIP). Two independent reviewers will read the full English text of the articles, screened and selected carefully, removing duplication. Then we evaluate the quality and analyses data by Review Manager (V.5.4). Results data will be pooled and meta-analysis will be conducted if there's 2 eligible studies considered.Results:This systematic review and meta-analysis will evaluate the value of the prediction models for the prognosis of DKA in the emergency department.Conclusions:This systematic review and meta-analysis will provide clinical basis for predicting the prognosis of DKA. It helps us to understand the value of predictive models in evaluating the early prognosis of DKA. The conclusions drawn from this study may be beneficial to patients, clinicians, and health-related policy makers.Study registration number:INPLASY202150023.

Time in blood glucose range 70 to 180 mg/dL and survival rate in critically ill patients: A retrospective cohort study.

BackgroundWhile time in targeted blood glucose range (TIR) 70–140 mg/dL is a known factor associated with mortality in critically ill patients, it remains unclear whether TIR is associated with 28-day mortality under the glycemic control with a less tight target glucose range of 70–180 mg/dL. We aimed to examine whether TIR 70–180 mg/dL was associated with 28-day mortality.MethodsThis is a retrospective cohort study using data from a tertiary care center in Japan collected from January 2016 through October 2019. We included adult patients (aged ≥20 years) admitted to the ICU. We excluded patients 1) with diabetic ketoacidosis patients, 2) discharged within 48 hours, 3) with repeated ICU admissions. We calculated TIR 70–180 mg/dL using the measured blood glucose values (≥3 times per day). The primary outcome was 28-day mortality. We examined the association between TIR and 28-day mortality using a logistic regression and Cox proportional hazard models with a stratification by glycosylated hemoglobin (HbA1c) level of 6.5%. Additionally, we repeated the analyses using the TIR category to assess the optimal TIR. For the sensitivity analysis, we repeated the primary analysis using TIR during the first three days from ICU admission.ResultsOf 1,230 patients, the median age was 72 years, 65% were male, and 250 patients (20%) had HbA1c ≥6.5% on admission. In patients with HbA1c <6.5%, TIR <80% was associated with an increased risk of 28-day mortality, with an adjusted odds ratio (OR) of 1.88 (95%CI: 1.36–2.61). Likewise, when using 10% incremental TIR as a categorical variable, lower TIR was associated with a worse 28-day mortality compared with TIR ≥90% (e.g., adjusted OR of TIR <60%, 3.62 [95%CI 2.36–5.53]). Similar associations were found in the analyses using Cox proportional hazards model and using TIR during the first three days. By contrast, in patients with HbA1c ≥6.5%, there was no consistent association of TIR with 28-day mortality.ConclusionsWe found that lower TIR 70–180 mg/dL was associated with a higher 28-day mortality in critically ill patients with HbA1c <6.5%, whereas there was no consistent association in patients with HbA1c ≥6.5%.

The Peruvian Experience: New-Onset Diabetes Presenting With Diabetic Ketoacidosis in Patients With COVID19 Infections

Introduction: Data has emerged about patients with T2DM may experience DKA and HHS if infected with SARS-CoV-2. There is limited data about new-onset diabetes in patients with COVID-19. We describe a case series of three Peruvian patients with new onset diabetes presenting with DKA who remained insulin dependent several months after infection resolution. Case 1: A 59-year-old man with no significant past medical history and normal glucose presented with fever and dyspnea for five days. He was hospitalized with hypoxemic respiratory failure and tested positive forCOVID19. Hypoxemia improved with supportive care, but on day three, he became lethargic, tachycardic, and tachypneic with 95% oxygen saturation on room air. Biochemistry revealed an anion gap metabolic acidosis with pH 7.3, bicarbonate 10 mmol/L (22–28), β-hydroxybutyrate 5.4 mmol/L (<0.5), and glucose 679 mg/dL. He was treated with continuous insulin infusion. After DKA resolved, he was transitioned to basal-bolus insulin and remained insulin-dependent during outpatient follow-up. Case 2: A 49-year-old man in good health prior to admission, was transferred to our hospital for acute respiratory failure and positive testing for SARS-CoV-2. Two days later he became confused, tachycardic, and tachypneic with 90% oxygen saturation. DKA was diagnosed based on a pH 7.1, bicarbonate 8 mmol/L, β-hydroxybutyrate 5 mmol/L and glucose 625 mg/dL. He was transferred to the ICU for continuous insulin infusion. After resolution of his DKA, subcutaneous insulin was started. Preadmission hemoglobin A1c was 4.5%. He remained on insulin post hospital discharge. Case 3: A 33-year-old man with normal glucose prior to admission was transferred to our hospital from an outpatient office with a two-day history of dyspnea and altered sensorium. He was tachycardic and tachypneic with 96% oxygen saturation on 3L nasal cannula. He tested positive for SARS-CoV-2. DKA was diagnosed with glucose 690 mg/dL, bicarbonate 4 mmol/L, serum β-hydroxybutyrate 5.8 mmol/L and pH 6.6. He was resuscitated with intravenous fluids and an insulin infusion was started. DKA resolved after 5 days and he was discharged home on subcutaneous insulin. He remained insulin-dependent on follow-up. Conclusion: New-onset diabetes with DKA due to SARS-CoV-2 is increasingly recognized, and beta-cell dysfunction can be permanent, resulting in insulin-dependent diabetes. Accordingly, our patients remained insulin-dependent several months post discharge.

Selecting Patients at Risk of Developing DKA on Gliflozins

Background: Since the introduction of gliflozins less than a decade ago we have witnessed how these medications are changing our approach to treating patients with type 2 diabetes mellitus. While recognizing tremendous benefits from these medication we are aware of potentially fatal risks. We present three cases of diabetic keto-acidosis in patients with type 2 diabetes mellitus and no prior history of diabetic emergencies while on SGLT2 inhibitors. Cases: A 58 year old woman with history of type 2 diabetes mellitus for 8 years and history of bulimia was treated with an SGLT2 Inhibitor for 12 months with stable control of diabetes mellitus. After an episode of very low calorie diet for 30 hours the patient was admitted to ICU with findings of diabetic ketoacidosis. She was critically ill but responded to treatment and needed only oral medication for future diabetic control. The second patient was a 49 year old man with type 2 diabetes mellitus and obesity who has been treated with oral antidiabetics for 7 years prior to requiring MDI insulin regimen in the past 3 years. The patient was well controlled in the past one year since introduction of SGLT2 inhibitors to his therapy. After a 2 day episode of eating carb heavy diet and using about 20% of prescribed insulin the patient developed DKA and was admitted to ICU where he needed to be intubated but improved and stabilized over the next few days. The third patient was a 52 year old man with history of type 2 DM for 13 years, well controlled in the past 3 years since SGLT2Is were added to his oral antidiabetic therapy. After one night of binge drinking alcohol with poor calorie intake the patient was diagnosed with DKA. After successful treatment this patient remains on oral antidiabetic medications. Conclusion: SGLT2Is have been prescribed in our clinic with great success since the first introduction of these medications. These are the only three patients who developed DKA on SGLT2 inhibitors in the past 6 years to our knowledge. All three patient had risk factors that were recognized but likely not enough emphasized. The first patient developed DKA during a “starvation phase” of eating disorder, the second one during a short episode of non-compliance with insulin while on a high carb diet and the third one after one episode of binging on alcoholic drinks. When prescribing SGLT2 inhibitors we are turning some patients with classical type 2 DM into ketosis prone diabetics. Eating disorders, extremely low or heavy carbohydrate intake, alcohol consumption and non-compliance with other antidiabetic medications should be subjects that we discuss when starting gliflozins in order to avoid significant risks. While using impressive benefits of these medications we should be aware of their side effects and recognize those that are at risk of serious side effects.

Euglycemic Diabetic Ketoacidosis in a Patient With Gestational Diabetes Mellitus and COVID-19 Infection

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening medical emergency requiring urgent treatment. Euglycemic DKA may occur in patients with both type 1 and type 2 Diabetes Mellitus (DM), as well as pregnancy. The absence of marked hyperglycemia can result in delayed diagnosis and treatment, resulting in potential adverse outcomes. Diabetes is a major comorbidity associated with severe hospital course and high fatality rate among patients with COVID-19 infection. We report our experience in a patient with gestational diabetes mellitus who developed euglycemic DKA and COVID-19 infection in her third trimester of pregnancy. Clinical Case: A 30-year-old lady at 29weeks gestation presented with two-day history of vomiting, diarrhea and abdominal pain. She reported good fetal movements. She had been diagnosed with Gestational Diabetes Mellitus (GDM) at 20 weeks gestational age, receiving treatment with multiple daily injections of insulin. 5 days earlier, she had tested positive for COVID-19 infection. She was asymptomatic; testing was performed as she had been in contact with a confirmed case. On examination she was afebrile and vitally stable, but dehydrated. Her initial laboratory investigations showed ketonemia with normal glucose level and normal anion gap. She was treated as a case of starvation ketosis and dehydration, with intravenous fluids and electrolyte replacement. However, 3 days later, the patient complained of worsening nausea and vomiting with dry cough and she developed hypotension. Chest X-ray showed bilateral mid and lowerzone pulmonary infiltrates. She was treated as COVID-19 pneumonia, received 2 units of COVID-19 convalescent plasma and broad-spectrum intravenous antibiotics. Repeated investigations showed worsening ketosis with high anion gap metabolic acidosis, consistent with a diagnosis of euglycemic DKA. Insulin infusion was initiated, isotonic saline with electrolyte replacement was also continued. She symptomatically improved over the next two days, with resolution of ketonemia and acidosis. The patient was discharged and she was well at her outpatient follow up visit. She underwent emergency Cesarean Section at 37 weeks gestational age, due to non-reassuring electronic fetal monitoring. She delivered a healthy female infant weighing 2445grams. Conclusion: Pregnancy is a high-risk period for DKA particularly when associated with other stressors that were identified in our patient – GDM, restricted calorie intake and COVID-19 infection. Diabetes is a risk factor for developing severe forms of COVID-19 and on the other hand, COVID-19 infection is associated with poor glycemic control and higher risk of hyperglycemic emergencies including ketoacidosis in diabetic patients. Prompt recognition of euglycemic DKA is critical in pregnancy, as this condition is associated with high fetal mortality rates.

A Case of Euglycemic Diabetic Ketoacidosis Following Canagliflozin Therapy

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM). In general, DKA characterized by blood sugar over 250 mg/dL, anion-gap metabolic acidosis, and increased plasma or urine ketones. Approximately 2–3% of DKA patients can present with normal blood glucose levels (less than 250 mg/dl) which called euglycemic DKA. Some of the etiologies of euglycemic DKA include recent use of insulin, low caloric intake, alcoholism, chronic liver disease, and pregnancy. Very rarely, SGLT2 inhibitor use may be responsible for euglycemic DKA. Case Presentation: Here we present a case of 44 years old female with a past medical history of DM type 2 who presented with acute onset of nausea and vomiting. Initial laboratory findings were remarkable for anion gap metabolic acidosis with a blood glucose level of 201 mg/dl. The patient was on long-acting insulin along with Canagliflozin and Metformin therapy over years and reported being compliant with medications. She was treated with intravenous insulin therapy which resolved acidosis as well as symptoms. The patient was discharged with recommendations of discontinuation of Canagliflozin. Discussion: SGLT2 inhibitors are the novel class of oral antidiabetic drugs which widely used due to their favorable cardiovascular and renal outcomes independent of glycemic control. However, their side effects remain a concern. DKA is a rare but serious side effect of SGLT2 inhibitors with an incidence rate of 9.4% in type 1 DM and less than 0.2% in type 2 DM. Patients typically present with euglycemia or low-grade hyperglycemia which results in a diagnostic challenge for treating physicians. SGLT2 inhibitors increase urinary glucose excretion with a subsequent decrease in circulating insulin and an increase in glucagon, rendering a metabolic shift from glucose to fatty acid utilization. During times of intercurrent illness (decreased oral intake, sepsis) or metabolic stress (surgery), decreased carbohydrate intake coupled with the aforementioned changes will result in decreased insulin secretion and increased counter-regulatory hormones including adrenaline and cortisol, promoting lipolysis, fatty acid oxidation, and ketone production by the liver which ultimately leading to euglycemic DKA. Conclusion: SGLT2 inhibitors induced euglycemic DKA treatment is identical to classic DKA with consideration of the lack of hyperglycemia. Appropriate patient counseling to ensure safe SGLT2 inhibitor therapy is crucial, including appropriate holding parameters during concomitant volume-depleting illnesses and decreased oral intake. Timely diagnosis of euglycemic DKA, and recognitions of other rare but lethal side effects to decrease overall morbidity and mortality.

Toxic soluble misfolded proteins and ER stress are present in plasma and vascular smooth muscle cells, respectively, from diabetic patients

Introduction Diabetes affects 425 million people worldwide, and is characterized by abnormal carbohydrate metabolism (hyperglycemia). Type 2 diabetes (T2D), characterized by variable degrees of insulin deficiency and resistance and is responsible for > 90% of cases of diabetes in adults. On the other hand, Type 1 diabetes (T1D) is an autoimmune disorder with an absolute deficiency of insulin. Diabetic Ketoacidosis (DKA) is the most common acute cause of morbidity and mortality in youth with T1D. The endoplasmic reticulum (ER) is the major cellular mechanism responsible for protein folding. Several factors such as hyperglycemia can disrupt ER homeostasis, resulting in ER stress and the unfold protein response (UPR). One class of toxic misfolded protein that can occur is soluble protein oligomers (SPOs). Persistent hyperglycemia is one of the main factors responsible for the pathogenesis of T1D and T2D complications. Based on this facts, we have hypothesized that SPOs are increased in the plasma sample from patients with DKA. Further, we wanted to know if soluble oligomers induce ER stress, or ER stress induces oligomers release. Methods By using the dot blotting approach, we measured SPOs in plasma from young (8 - 18 years old) male (n=4) and female (n=6) DKA patients in three different time points: (a) initial 6 -12 hours of treatment; (b) 2-3 weeks post-DKA correction; (c) 3 months post-DKA correction. Mechanistically, we evaluated if vascular smooth muscle cells (VSMCs) from the tibial artery of a 45 year old male with T2D presents with ER stress and/or SPOs in the media. VSMCs was treated with ER stress inhibitor (4-PBA, 2 mmol/L), SPOs inhibitor (K01-162, 10 µmol/L) or vehicle (DMSO) for 48 hours. Results SPOs were present in plasma from male and female patients with DKA at all-time points. Interestingly, SPOs levels increased in a time-dependent manner in females, but not males (Figure 1). On the other hand, SPOs were not detected in the media of VSMCs from a patient with T2D. However, the C/EBP Homologous Protein (CHOP), a marker for ER stress, was expressed in VSMC from this patient, and the treatment with ER stress inhibitor, PBA, but not SPOs inhibitor, K01-162, decreased its expression (A.U.: Vehicle: 55.3 ± 5 vs. PBA: 40.1± 5 * vs. K01-162: 64.3 ± 9; *p=0.04 vs. Vehicle). Conclusion Here we propose that in diabetes, there is an accumulation of toxic misfolded proteins in the form of SPOs that may contribute to the systemic inflammation observed in young patients with DKA. Although VSMC presents ER stress, this tissue may not be the main source of SPOs, at least in vitro or in the absence of hyperglycemia. These data have promising clinical implications as it proposes a novel mechanism that can be exploited as a therapeutic target in diabetes and DKA.

ACUTE PANCREATITIS IN PATIENTS WITH DIABETIC KETOACIDOSIS PRESENTING AT A TERTIARY CARE UNIT

Objective: To determine the frequency of acute pancreatitis among the patients diagnosed with diabetic ketoacidosis at our tertiary care hospital.&#x0D; Study Design: Co-relational study.&#x0D; Place and Duration of Study: Medicine department, Pak Emirates Military Hospital Rawalpindi, from Jun to Dec 2019.&#x0D; Methodology: A total of 40 cases presenting with diabetic ketoacidosis were included in our study. Diabetic ketoacidosis was diagnosed by consultant medical specialist. All patients underwent baseline investigations including serum amylase, lipid profile and CT scan abdomen in order to diagnose acute pancreatitis. Relationship of age, gender, duration of diabetes mellitus and triglyceride levels was assessed with the presence of acute pancreatitis among the patients of diabetic ketoacidosis.&#x0D; Results: A total of forty patients were managed as diabetic ketoacidosis in our hospital during the study period. Out of them 8 (20%) had acute pancreatitis while 32 (80%) were not diagnosed with acute pancreatitis. Confusion (55%) was the commonest presenting complaint followed by abdominal pain (25%). With binary logistic regression analysis, we found that female gender and raised triglyceride levels had a statistically significant relationship with presence of acute pancreatitis among the patients of diabetic ketoacidosis included in this study.&#x0D; Conclusion: Considerable number of patients were diagnosed with acute pancreatitis who presented with diabetic ketoacidosis. Special attention should be paid towards female patients and those with raised triglyceride levels to look for the sign and symptoms of acute pancreatitis in order to diagnose and manage this condition.

POS-087 ACUTE METABOLIC ACIDOSIS IN ALCOHOL ABUSERS IS HIGHLY ASSOCIATED WITH LACTIC ACIDOSIS

It has long been known that alcohol abuse combined with dehydration and starvation causes acute metabolic acidosis. Recently, it has attracted attention because of its pathogenic similarity to SGLT2i-induced euglycemic ketoacidosis. In these conditions, the accumulation of acids, specifically lactic acid, other than ketones is considered rare except in special circumstances, such as sepsis and vitamin deficiencies. However, its incidence in clinical practice seems to be more frequent. Therefore, we reviewed the present situation at our hospital to determine the etiology of lactic acid accumulation. From January 2013 to June 2020, we extracted data of patients with blood gas conditions of pH <7.30 and HCO3 <18 mEq/l in our hospital. Then, we defined cases with documented illnesses suggestive of alcohol abuse and a clear indication of prior heavy drinking as the alcohol-related acidosis (AIA) group. To understand the direct effect of alcohol, cases with proven infection were excluded. As a control, diabetic ketoacidosis (DKA) patients >18 years of age with the same blood gas condition were included. In 7.5 years, 28,697 blood gas analyses were performed, of which 1404 met the defined blood gas conditions. Among them, 25 AIA and 20 DKA patients met the inclusion criteria. Urinary ketones were 90% and 67% positive in DKA and AIA patients, respectively. As expected, lactate was significantly higher in AIA than in DKA (16.4 ± 8.4 vs. 4.6 ± 2.7 mmol/l p<0.001). There was no difference in oxygenation or renal function between the two groups at the time of admission. However, blood pressure and blood glucose levels were lower and liver deviation enzymes were higher in the AIA group than in the DKA group. Although in AIA, lactic acid is thought to be a contributing factor for circulatory failure due to dehydration, there was no significant difference in the amount of fluid infused up to 6 h from the start of treatment between the two groups (2.6 L in AIA vs. 3.0 L in DKA, p=0.4). Additionally, there was no difference in the time from the start of treatment to improvement in acidosis (pH>7.3. 6.7 h in AIA and 7.5 h in DKA, p=0.5). Moreover, there was no correlation between the amount of fluid and time to improve acidosis in the 22 AIA patients who were treated with fluid alone (r = -0.004). Among study participants divided into two groups according to median fluid intake in the AIA group (mean 1.3. vs. 3.9 L / 6 hours, respectively; p<0.001), there was no difference in time to improvement in acidosis (7.0 vs. 6.2 hours, p=0.6) Acute metabolic acidosis that occurs in alcohol abusers was accompanied by a high frequency of lactic acid accumulation and ketones. Furthermore, the standard therapy of dehydration correction was not an effective treatment. Recently, in the area of sepsis, it is believed that the cause of elevated lactate is not circulating insufficiency but overproduction due to adrenaline stimulation or decreased excretion due to hepatic and renal damage; therefore, excessive fluid infusion should be avoided. These results suggest that alcohol-induced lactic acid accumulation may be due to similar reasons.

POS-106 A NOT SO SWEET COMPLICATION OF DIABETES MELLITUS THERAPY(EUGLYCEMIC DKA)

Diabetic ketoacidosis (DKA) is the most feared and well-known life-threatening complication of diabetes generally due to noncompliance or an active infectious process. But, what if DKA were to take place with adequate medication adherence? Euglycemic diabetic ketoacidosis is a clinical diagnosis that encompasses an increased anion gap metabolic acidosis, ketonemia or ketonuria in the setting of normal blood glucose levels (<200 mg/dL). This entity is a diagnostic challenge as euglycemia cover-ups the underlying diabetic ketoacidosis. Seeing as how sodium-glucose cotransporter 2 (SGLT2) inhibitor use has increased following studies that demonstrate its cardioprotective and renoprotective effects a high index of clinical suspicion is warranted now more than ever, and other diagnosis must be ruled out. This is the case of a 66 y/o male patient with past medical history of type 2 diabetes mellitus on empagliflozin, insulin and metformin, arterial hypertension, major depressive disorder, dyslipidemia who was initially admitted to a psychiatric hospital for management of depression and psychosis. Two days after admission he presented with diffuse abdominal discomfort associated with nausea, vomiting, poor appetite and difficulty voiding for which he was transferred to our institution for Internal Medicine evaluation. After evaluation at the Emergency Department he was admitted to IM ward with diagnostic impression of acute prostatitis and obstructive uropathy. Initial laboratories were remarkable for WBCs at 9.4x10-3uL, no bandemia and no neutrophilia, adequate hemoglobin and platelet count. Chemistry with Glucose at 136mEq/L, Potassium at 4.5mEq/L, HCO3 at19mEq/L, normal hepatic enzymes, normal lactic acid and normal pancreatic enzymes. Laboratories the next morning revealed glucose 127 mg/dL, bicarbonate 14 mEq/L with a pure high anion gap metabolic acidosis of 23mEq/L (delta-delta of 1.1), beta-hydroxybutyrate at 65mg/dL, normal lactate 0.8 mmol/L, negative toxicology and arterial blood gases revealing metabolic acidosis with adequate respiratory compensation (pH 7.314, pCO2 31.3 mmHg and bicarbonate 15.5 mmol/L). Diagnosis of euglycemic DKA secondary to empagliflozin precipitated by acute bacterial prostatitis and decreased oral intake was made. Patient subsequently transferred to t he medical intensive care unit where crystalloid volume expansion was provided, DKA protocol with intravenous insulin infusion initiated along with D10W intravenous fluid administration. After approximately 16 hours of treatment, metabolic acidosis and anion gap normalized. Patient was successfully discharged home after completion of antibiotherapy with follow up with his primary care physician. Euglycemic DKA secondary to SGLT2i is a diagnosis often missed by physicians accustomed to seeking for elevated blood sugars. Its presentation is often vague and insidious for which cases are underreported and incidence remains unknown. Nonetheless, ketoacidosis in diabetic patients remains a medical emergency despite euglycemia. High clinical suspicion is warranted in order to begin prompt treatment and reduce hospital stay as well as associated costs.

COVID-19 and Diabetic Ketoacidosis: Report of Eight Cases.

AimTo describe the clinical characteristics and outcome of hospitalized COVID-19 patients with diabetic ketoacidosis (DKA).MethodsWe report eight cases of diabetic ketoacidosis in COVID-19 who presented to our institution in New Jersey, USA. COVID-19 was diagnosed by nasopharyngeal swab reverse transcription polymerase chain reaction (RT-PCR). The patients' electronic medical records were reviewed. Data on patients' age, sex, ethnicity, laboratory values, glycosylated hemoglobin level, oral antihyperglycemic agents (OHAs), insulin, and clinical outcomes were collected.ResultsThe median age of the patient was 42.5 years, and seven were males and one was female. Out of eight patients, five had type 2 diabetes mellitus (DM), two had undiagnosed DM, and one had type 1 DM. Median value of initial glucose on presentation was 454 mg/dL. Median value of HbA1c on presentation was 11.4% and of anion gap was 26.5 mEq/L. Four patients had large ketonemia, one patient had moderate ketonemia, and three patients had small ketonemia. All the patients were started on standard treatment protocol for DKA with intravenous fluids and IV insulin infusion. Acute kidney injury (AKI) was seen in four patients, and one patient required renal replacement therapy. Out of eight patients, three required mechanical ventilation, and the same three patients died.ConclusionOur case series shows that COVID-19 infection can precipitate DKA in patients with known diabetes mellitus patients or as a first manifestation in undiagnosed DM patients; COVID-19 with DKA is associated with substantial mortality. Further studies are needed to characterize poor risk factors associated with mortality in these patients.

Predictors of new-onset diabetic ketoacidosis in patients with moderate to severe COVID-19 receiving parenteral glucocorticoids: A prospective single-centre study among Indian type 2 diabetes patients

Background and aimCOVID-19 infection predisposes to diabetic ketoacidosis(DKA); whether glucocorticoids enhances this risk is unknown.We aimed to study the occurrence of DKA after initiating glucocorticoids in patients with type 2 diabetes mellitus(T2DM) and moderate-to-severe COVID-19, and identify predictors for it. MethodsPatients with T2DM and moderate or severe COVID-19 infection were prospectively observed for development of new-onset DKA for one week following initiation of parenteral dexamethasone. Clinical and biochemical parameters were compared between those who developed DKA (Group A) and those who didnot (Group B). Logistic regression was done to identify independent risk-factors predicting DKA; ROC-curve analysis to determine cut-offs for the parameters in predicting DKA. ResultsAmongst 302 patients screened, n = 196 were finally included, of whom 13.2% (n = 26,Group A) developed DKA. Patients in Group A were younger, had lower BMI, increased severity of COVID-19 infection, higher HbA1c%, CRP, IL-6, D-dimer and procalcitonin at admission (pall < 0.02). Further, admission BMI (OR: 0.43, CI: 0.27–0.69), HbA1c % (OR: 1.68, CI: 1.16–2.43) and serum IL-6 (OR: 1.02, CI: 1.01–1.03) emerged as independent predictors for DKA. Out of these, IL-6 levels had the highest AUROC (0.93, CI: 0.89–0.98) with a cut-off of 50.95 pg/ml yielding a sensitivity of 88% and specificity of 85.2% in predicting DKA. ConclusionThere is significant incidence of new-onset DKA following parenteral glucocorticoids in T2DM patients with COVID-19, especially in those with BMI <25.56 kg/m2, HbA1c% >8.35% and IL-6 levels >50.95 pg/ml at admission.

A Prediction Model of Mortality in Patients Hospitalized with Diabetic Ketoacidosis in a Tertiary Referral Hospital in Surabaya, Indonesia

Background: The mortality rate of diabetic ketoacidosis (DKA) remains high in Indonesia. Differentpatterns were contributing to DKA mortality from previous studies. We aim to identify clinical and laboratoryfindings as mortality predictors of DKA.Methods: This retrospective study was conducted in a tertiary referral hospital in Surabaya. Medical recordsof DKA patients from January 2016 to December 2018 were analyzed. Clinical and laboratory data wereobtained from medical records for three years period. Clinical outcome was defined as either dischargedhome or death.Results: Fifty-six among 116 DKA patients did not survive during hospitalized. Age of 60 or older, thedepressed mental state with GCS below 13, potassium serum less than 3.5 mmol/L, and bicarbonate serumless than 15 mmol/L are found to be significant as independent factors of mortality in DKA patients.Conclusion: The mortality rate of DKA patients in this study is still high. It independently associatedwith the age of 60 years or older, depressed mental state, hypokalemia, and low bicarbonate level. Earlystratification of these predictors would help to treat patients accordingly.