Episodes Of Diabetic Ketoacidosis Research Articles

S2282 Black Esophagus Manifesting as Upper Gastrointestinal Bleeding in Diabetic Ketoacidosis: A Case Report

Introduction: Acute esophageal necrosis, or black esophagus, is a rare clinical entity manifesting as upper gastrointestinal bleeding and complicating various conditions. However, black esophagus in the setting of diabetic ketoacidosis (DKA) has been rarely reported. We present a case of a 36-year-old male with black esophagus presenting as hematemesis complicating an episode of DKA. Case Description/Methods: A 36-year-old male with uncontrolled type 1 diabetes mellitus complicated by end-stage renal disease and hypertension presented to the emergency department with abdominal pain, nausea, and vomiting. Patient reported worsening abdominal pain and associated blood-tinged emesis. On presentation, patient was hemodynamically stable. Physical exam included an abdomen that was diffusely tender to palpation without peritoneal signs. Initial labs remarkable for serum glucose 1491, anion gap 41, bicarbonate 9, and hemoglobin 7.5. Patient was admitted to Critical Care for insulin drip and intravenous fluid resuscitation for DKA. Later, patient had an episode of hematemesis resulting in tachycardia, hypotension, and drop in hemoglobin to 5.6. Patient was further resuscitated with blood transfusions with improvement in hemodynamics and hemoglobin to 8.9. Continuous pantoprazole infusion was initiated. Upper endoscopy demonstrated severe, ulcerative necrotizing circumferential esophagitis in the middle and lower third esophagus and a medium size blood clot without evidence of active bleeding. No biopsies were taken due to concern for possible false lumen; CT chest with contrast demonstrated no signs of esophageal perforation. Following EGD, patient had several small self-limiting episodes of hematemesis and melena, while maintaining hemodynamics. He was continued on pantoprazole infusion and placed on strict nothing by mouth (NPO) precautions for 3 days with gradual advancement of diet. He received 6 days of empiric antimicrobial therapy with ampicillin-sulbactam and fluconazole. Patient reported no further episodes of hematemesis. Hemoglobin stabilized around 8.0 (Figure). Discussion: DKA is a rare but life-threatening cause of acute esophageal necrosis which may develop due to a combination of tissue hypoperfusion, impaired mucosal defenses, and gastric reflux. Upper gastrointestinal bleeding in the setting of DKA should raise suspicion for black esophagus which is a potential cause of mortality. Early diagnosis and treatment of underlying etiology are the key factors in management.Figure 1.: Severe, ulcerative necrotizing circumferential esophagitis in the middle and lower third esophagus and a medium size blood clot without evidence of active bleeding.

Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes

BackgroundCurrently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting.MethodsIn this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed.ResultsA total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, −0.5 percentage points; 95% confidence interval [CI], −0.6 to −0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, −0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P=0.39). No episodes of diabetic ketoacidosis occurred in either group.ConclusionsIn this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.)

A Literature Review of the Therapeutic Perspectives of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor-Induced Euglycemic Diabetic Ketoacidosis.

Euglycemic diabetic ketoacidosis (DKA), a side effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors, is a triad of high metabolic anion gap acidosis, raised serum and urine ketones, and serum glucose <250 mg/dl. SGLT2 inhibitors cause a carbohydrate deficit by glucosuria, which leads to an increased glucagon/insulin ratio, the metabolic shift from glucose to lipid utilization causing ketogenesis, and hence euglycemic DKA. Additional factors like the ketogenic diet, illness, surgery, and pregnancy contribute to precipitating these episodes. Keywords searchincluded "Euglycemic DKA and SGLT2 inhibitors" in PubMedand Google Scholar, to compile data from existing articles that provide information on the withholding and restarting period of the drug after a euglycemic DKA episode. SGLT2 inhibitors, used in the treatment of type 2 DM, have an average half-life of 11-13 hours, so most articles suggested withholding the drug three days before any elective surgery but some articles suggested a longer withholding period based on other precipitating factors contributing to euglycemic DKA. Hence, we came up with patient inclusion criteria and concomitant therapies review that we need to consider in making this decision. In addition, a multidisciplinary approach is required when laying out guidelines for restarting the drug to have a unanimous approach. After reviewing the existing literature, it is clear that concrete guidelines are required to decide on drug withholding and restarting periods after a euglycemic DKA episode, as they vary among different institutions and different specialties. We believe it is crucial to consider patient inclusion criteria and concomitant therapies in forming those guidelines.

DKA Prevention and Insulin Pumps: Lessons Learned From a Large Pediatric Pump Practice.

This purpose of the study was to describe recent diabetic ketoacidosis (DKA) incidence data in youth with type 1 diabetes using insulin pumps and the impact of continuous glucose monitors (CGMs) on DKA rates. DKA data were obtained through a retrospective chart review of insulin pump users (ages <26 years) between December 2019 and June 2021 in an academic pediatric endocrinology practice where 68% of patients were pump users. Among 591 pump patients, 28 events occurred (3.16 events per 100 patient-years). Mean age was 13.6±3.4 years; 85.7% ranged from 12 to 19 years. Mean A1C was 10.2±2.3%, diabetes duration was 6.1±4.0 years, and 57.1% used CGM. Admission pH levels ranged between 7.0 and 7.31, with 28.6% of events classified as "moderate" and 46.4% "severe." There was no significant difference in the DKA severity between those who wore a CGM and those who did not (ie, pH, serum bicarbonate, mentation alteration, length of stay, intensive care unit admission, and hospital admission). DKA events were attributed to concurrent illness (10.7%), insulin omission (14.3%), pump site failure (57.1%), or other pump malfunctions (14.3%). DKA events in pump-treated patients were relatively uncommon; most episodes occurred in adolescents with higher A1C levels, and notably, most events could have been avoided if users followed standard troubleshooting guidelines. Thus, DKA prevention education should be reinforced at each encounter, particularly for teens with higher A1C levels. Moreover, more than 50% of those with DKA episodes wore a CGM, suggesting that pump users using CGM require frequent reinforcement of this education and that the development of such educational materials is critical.

Estimated Cost-effectiveness of Subcutaneous Insulin Aspart in the Management of Mild Diabetic Ketoacidosis Among Children

Intravenous (IV) insulin infusion is the standard of care for treating diabetic ketoacidosis (DKA) worldwide. Subcutaneous (SC) insulin aspart could decrease the use of health care resources. To compare the cost-effectiveness of mild uncomplicated DKA management with SC insulin aspart vs IV insulin infusion among pediatric patients from the perspective of a public health care payer using clinical data. This economic evaluation included children aged 2 to 14 years presenting to the emergency department of a single academic medical center with mild DKA between January 1, 2015, and March 15, 2020. The medical records for DKA treatment course and its associated hospitalization costs were reviewed. Data were analyzed from January 1, 2015, to March 15, 2020. Subcutaneous insulin aspart vs IV regular insulin infusion. The incremental cost-effectiveness ratio (US dollars per hour), duration of DKA treatment, and length of hospital stay. A total of 129 children with mild DKA episodes (mean [SD] age, 9.9 [3.1] years; 72 girls [55.8%]) were enrolled in the study. Seventy children received SC insulin aspart and 59 received IV regular insulin. Overall, the length of hospital stay in the SC insulin group was reduced (mean, 16.9 [95% CI, -31.0 to -2.9] hours) compared with the IV insulin group (P = .005). The mean (SD) cost of hospitalization in the SC insulin group (US $1071.99 [US $523.89]) was less than that in the IV insulin group (US $1648.90 [US $788.03]; P = .001). The incremental cost-effectiveness ratio was -34.08 (95% CI, -25.97 to -129.82) USD/h. The use of SC insulin aspart was associated with a lower likelihood of prolonged hospital stay (β = -17.22 [95% CI, -32.41 to -2.04]; P = .03) than IV regular insulin when controlling for age and sex. Findings of this economic evaluation suggest that SC insulin aspart is dominant vs IV regular insulin in the management of mild uncomplicated DKA in children.

Faster Insulin Aspart for Continuous Subcutaneous Insulin Infusion: Is It Worth It?

IntroductionFaster insulin aspart (fASP) is the new formulation of insulin aspart (ASP) with a left-shifted pharmacokinetic profile, allowing better control of early postprandial hyperglycemia and a reduction in the risk of late post-meal hypoglycemia. However, it can be associated with more frequent infusion set changes. The purpose of this study is to evaluate efficacy and safety one, three, and six months after starting fASP in continuous subcutaneous insulin infusion (CSII) systems.MethodsThis is a retrospective study that included adults with type 1 diabetes mellitus, users of CSII ≥3 months, who started fASP. Exclusion criteria included less than one month of follow-up after the intervention, concomitant initiation of pharmacological therapy, pre-conception period, and non-use of continuous glucose monitoring.ResultsA total of 77 individuals were included, of which 52 (67.5%) were female, aged 39.87 ± 13.10 years, with a mean time under CSII of 7.30 ± 3.58 years and a median follow-up time after transition to fASP of six months. There was a trend to a global glycemic control improvement at six months after starting fASP: numeric increase in time in range (56.40 ± 12.62% vs 60.15 ± 13.53%, p=0.148), reduction in time above range (37.76 ± 13.05% vs 34.67 ± 14.94%, p=0.557), time below range (6.00 (5.00)% vs 4.50 (5.25)%, p=0.122), and mean glucose (174.29 ± 25.14 mg/dL vs 167.00 ± 25.30 mg/dL, p=0.207). There was a reduction in body mass index (BMI) at six months after switching to fASP (25.08 (4.59) kg/m2 vs 24.45 (3.05) kg/m2, p=0.010), despite the absence of a significant variation in total daily insulin. Adverse event and discontinuation rates were 7.8% and 6.5%, respectively, with no documented episodes of diabetic ketoacidosis or severe hypoglycemia.ConclusionsfASP proved to be a safe and effective therapeutic option in CSII systems associated with a significant BMI reduction, aspects that might justify its preference.

Analysis of Apoptotic, Clinical, and Laboratory Parameters in Type 1 Diabetes and Early Diabetic Nephropathy: Clustering and Potential Groups Evaluation for Additional Therapeutic Interventions

Objective:Type 1 diabetes (T1D) is one of the most prevalent chronic illnesses diagnosed in childhood. Diabetic nephropathy (DN) is one of the commonest complication of T1D. Therefore the development of specific treatment that arrests progression of DN based on an individual approach would be beneficial. Analysis of criteria of apoptosis, and clinical, and laboratory characteristics in T1D and early DN in the framework of clustering may be helpful in the identification of potential groups for additional therapeutic interventions.Methods:A survey of 104 children (62 males, 42 females) with T1D and DN aged 2 to 17 years in the Endocrinology unit of Clinical Pediatric Hospital No 6 (Kyiv, Ukraine) was performed. Clinical data (age, gender, disease duration, blood pressure), conventional laboratory markers including complete blood count, serum cholesterol, hemoglobin A1c (Hb1Ac), glomerular filtration rate (GFR), and microalbuminurea (MAU), and markers of apoptosis (BcL-xL, caspase-3) and transcriptional factor HIF-1alfa were analyzed.Results:A cluster group in T1D children was characterized by somewhat higher number of platelets (PLT) - 344.9±7.88·109/L, increased GFR up to hyperfiltration level 124.5±8.86 mL/min/1.73 m2 and decreased anti-apoptotic defense - BcL-xL 144.9±2.35 a.u. was identified. Children with DN may be divided into three groups based on age, body mass index, systolic blood pressure, PLT count, erthyrocyte sedimentation rate, albumin/globulin ratio, serum cholesterol, Hb1Ac, number of diabetic ketoacidosis (DKA) episodes, GFR, MAU, HIF-1alfa, Bcl-xL, caspase-3 levels. Among children with early DN a cluster characterized by the following parameters was found: PLT count - 311.±12.05·109/L, frequency of DKA episodes - 4.82±0.26 episodes/year, MAU - 112.0±10.12 mm/24 h, HIF - 200.5±3.49 a.u., BcL-xL - 128.8±3.1 a.u., and caspase-3 - 159.6±5.5 a.u.Conclusion:Thus, we hypothesize that T1D pediatric patients with increased PLT count, hyperfiltration and reduced anti-apoptotic defense may represent a group for additional therapeutic interventions, such as antioxidants along with stndard therapies to achieve optimal glycemic control. Within the DN group there was a sub-group with somewhat increased PLT count, high frequency of DKA episodes/year, high MAU, prominent increase in HIF level, prominent disturbances in apoptosis controlling factors BcL-xL and caspase-3 tht may require additional therapeutic interventions, again including antioxidants, but may additionally benefit from anti-apoptotic effectors along with optimal glycemic control, and management of hypertension and albuminuria.

Mortality after discharge from hospital following an episode of diabetic ketoacidosis.

The rate of inpatient mortality associated with diabetic ketoacidosis (DKA) has steadily decreased in recent decades. However, there remains a significantly increased outpatient death rate following an episode ofsurvived DKA. We undertook this study to investigate theobserved increase in mortalityfollowing an episode of DKA. We completed a retrospective cohort study to investigate rates and causes of death in people admitted to our hospital with DKA between 2013 and 2018. DKA was confirmed by pre-defined biochemical parameters and cause of death data was extracted from multiple sources. Follow-up was for two years after discharge for all participants with one-year mortality being the main time point for analysis. We identified 818 admissions to hospital with DKA, affecting 284 people. Twenty people died as inpatients and a further 40 people died during the two-year follow-up. Of these 60 participants, cause of death was able to be determined for 41 (68%), with most deaths occurring due to infection or macrovascular disease. Risk factors for death within a year of hospital discharge included older age, vascular complications of diabetes, intellectual impairment and residential care living. Those who survived an episode of DKA had a one-year age-corrected mortality rate 13 times higher than the general population. This was more marked in the younger cohort with those aged 15-39years being 49 times more likely to die in the year after surviving a DKA admission compared to their general population counterparts. An episode of diabetic ketoacidosis is associated with a significant outpatient mortality risk with most deaths due to infectious or macrovascular causes. This study should prompt investigation of predictive scoring tools to identify those at increased mortality risk after DKA and encourage the development of targeted interventions to reduce mortality.

A user preference analysis of commercial breath ketone sensors to inform the development of portable breath ketone sensors for diabetes management in young people.

BackgroundPortable breath ketone sensors may help people with Type 1 Diabetes Mellitus (T1DM) avoid episodes of diabetic ketoacidosis; however, the design features preferred by users have not been studied. We aimed to elucidate breath sensor design preferences of young people with T1DM (age 12 to 16) and their parents to inform the development of a breath ketone sensor prototype that would best suit their diabetes management needs.Research designs and methodsTo elicit foundational experiences from which design preference ideas could be generated, two commercially available breath ketone sensors, designed for ketogenic diet monitoring, were explored over one week by ten young people with T1DM. Participants interacted with the breath ketone sensing devices, and undertook blood ketone testing, at least twice daily for five days to simulate use within a real life and ambulatory care setting. Semi-structured interviews were conducted post-testing with the ten young participants and their caregivers (n = 10) to elicit preferences related to breath sensor design and use, and to inform the co-design of a breath ketone sensor prototype for use in T1DM self-management. We triangulated our data collection with key informant interviews with two diabetes educators working in pediatric care about their perspectives related to young people using breath ketone sensors.ResultsParticipants acknowledged the non-invasiveness of breath sensors as compared to blood testing. Affordability, reliability and accuracy were identified as prerequisites for breath ketone sensors used for diabetes management. Design features valued by young people included portability, ease of use, sustainability, readability and suitability for use in public. The time required to use breath sensors was similar to that for blood testing. The requirement to maintain a 10-second breath exhalation posed a challenge for users. Diabetes educators highlighted the ease of use of breath devices especially for young people who tended to under-test using blood ketone strips.ConclusionsBreath ketone sensors for diabetes management have potential that may facilitate ketone testing in young people. Our study affirms features for young people that drive usability of breath sensors among this population, and provides a model of user preference assessment.

Diabetic ketoacidosis incidence among children with new-onset type 1 diabetes in Poland and its association with COVID-19 outbreak-Two-year cross-sectional national observation by PolPeDiab Study Group.

BackgroundThere are several observations that the onset of coronavirus 19 (COVID‐19) pandemic was associated with an increase in the incidence of diabetic ketoacidosis (DKA). However, due to heterogeneity in study designs and country‐specific healthcare policies, more national‐level evidence is needed to provide generalizable conclusions.ObjectiveTo compare the rate of DKA in Polish children diagnosed with type 1 diabetes (T1D) between the first year of COVID‐19 pandemic (15 March 2020 to 15 March 2021) and the preceding year (15 March 2019 to 15 March 2020).MethodsReference centers in 13 regions (covering ~88% of Polish children) retrospectively reported all new‐onset T1D cases in children from assessed periods, including DKA status at admission, administered procedures and outcomes. Secondly, we collected regions' demographic characteristics and the daily‐reported number of COVID‐19‐related deaths in each region.ResultsWe recorded 3062 cases of new‐onset T1D (53.3% boys, mean age 9.5 ± 4.3 years old) of which 1347 (44%) had DKA. Comparing pre‐ and post‐COVID‐19 period, we observed a significant increase in the rate of DKA (37.5%–49.4%, p < .0001). The fraction of moderate (+5.4%) and severe (+3.4%) DKA cases increased significantly (p = .0089), and more episodes required assisted ventilation (+2.1%, p = .0337). Two episodes of DKA during 2020/2021 period were fatal. By region, change in DKA frequency correlated with initial COVID‐19 death toll (March/April 2020) (R = .6, p = .0287) and change in T1D incidence (R = .7, p = .0080).ConclusionsThe clinical picture of new‐onset children T1D in Poland deteriorated over a 2‐year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID‐19 epidemic.

Incidence and factors associated with acute kidney injury among children with type 1 diabetes hospitalized with diabetic ketoacidosis: A prospective study.

Acute kidney injury (AKI) is frequent among critically ill children. This study aimed to assess the incidence and factors associated with AKI among children with type 1 diabetes mellitus (T1DM) hospitalized with diabetic ketoacidosis (DKA). This prospective observational study was conducted at Sohag University Hospital, Egypt over 1 year. Children aged 6 months to 12 years, diagnosed with T1DM and hospitalized with the criteria of DKA were included. The study participants received intravenous fluid therapy and intravenous insulin infusion for DKA management. Serum creatinine levels were measured at admission, 24 and 48 h after admission. AKI was defined and staged using the Kidney Disease Improving Global Outcomes serum creatinine criteria. The study included 265 DKA episodes in 240 participants. AKI was found in 110 (41.5%) DKA episodes. Moderated to severe AKI developed in 41 (15.5%) episodes. Multivariate regression analysis revealed that age (adjusted odds ratio=0.78, 95% confidence interval (CI): 0.69-0.89, p< 0.001), Glasgow-Coma scale (GCS) < 14 at admission (adjusted odds ratio=4.66, 95% CI: 1.66-13.14, p= 0.004) and serum chloride level at 12 h (adjusted odds ratio=1.10, 95% CI: 1.02-1.18, p= 0.01) were the most significant factors associated with moderate to severe AKI development. AKI is common among T1DM children hospitalized with DKA. Younger age, low GCS at hospital admission and increased serum chloride level during DKA management were associated with increased risk for moderate to severe AKI development.

Precipitating factors of diabetic ketoacidosis in type 1 diabetes patients at a tertiary hospital: a cross-sectional study with a two-time-period comparison.

To evaluate the precipitating factors of diabetic ketoacidosis (DKA) in patients with type 1 diabetes hospitalized through the emergency department of a tertiary hospital. Individuals with type 1 diabetes hospitalized for DKA from January 2005 to March 2010 (first period [P1], n = 75) and from April 2010 to January 2017 (second period [P2], n = 97) were identified through a query of electronic medical records. Data were collected by reviewing medical records. Only the first hospitalization of each participant in each period was included. In P2, 44 patients (45.4%) were women, mean age was 26.2 ± 14.5 years, and 74 patients (76.3%) had a previous diagnosis of type 1 diabetes. Only 1 patient had glycated haemoglobin (HbA1c) below 64 mmol/mol (8.0%). Most patients (62.2%) had had a previous episode of DKA. In P1, non-adherence was the main cause of DKA (38.7%), followed by infection (24.0%). In P2, these rates were 34.0% and 24.7%, respectively; no statistical difference was observed between the two study periods (p = 0.790). Over time, non-adherence remained the main precipitating factor of DKA, followed by infection, and no significant difference was observed between the two study periods. Elevated HbA1c, outside the therapeutic range, indicates suboptimal diabetes care and may explain, at least in part, poor adherence as a precipitating factor of decompensation. Health strategies, such as improved self-management of type 1 diabetes, may contribute to a future reduction in DKA episodes.

33-OR: ADA Presidents' Select Abstract: Glycemic Outcomes over 12 Months in Very Young Children with the Omnipod 5 Automated Insulin Delivery (AID) System

The Omnipod 5 AID System is a tubeless hybrid closed-loop system with on-body operation and customizable glucose targets. Safe and effective system use was demonstrated in children aged 2-5.9y with type 1 diabetes (T1D) during a 3-mo pivotal study. To evaluate durability of glycemic benefit, we analyzed results from 9mo of an ongoing extension study, totaling 12mo of system use. In the pivotal study, participants used the system for 3mo at home, after 14d of their standard therapy (ST, pump or multiple daily injections) . They were then invited to participate in the extension study. Safety endpoints were occurrence of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) . Glycemic outcomes were A1C and percent time in ranges (TIR 70-180 mg/dL, TBR &amp;lt;70 mg/dL, TAR &amp;gt;180 mg/dL) during 3-mo AID intervals compared with ST. All pivotal trial participants (N=80) , aged (mean±SD) 4.7±1.0y with T1D duration 2.3±1.1y and total daily insulin of 14±4U (range: 5.3-27U) at baseline, enrolled in the extension. Improved outcomes were observed for up to 12mo, including lower A1C and greater TIR during each AID interval compared with ST (all p&amp;lt;0.05, Table) . There were no episodes of DKA or SH in the 12-mo study. The safety and improved glycemic outcomes from the initial 3mo pivotal study persisted for an additional 9mo, indicating the potential long-term benefit of the Omnipod 5 System in very young children with T1D. Disclosure D.Desalvo: Consultant; Dexcom, Inc., Insulet Corporation, Research Support; Insulet Corporation. D.W.Hansen: None. T.T.Ly: Employee; Insulet Corporation, Stock/Shareholder; Insulet Corporation. Omnipod 5 in preschoolers study group: n/a. B.W.Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc., Diasome, Dompé, Eli Lilly and Company, Insulet Corporation, IQVIA Inc., Jaeb Center for Health Research, Medtronic, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanvita Medical, Senseonics, ViaCyte, Inc., Speaker's Bureau; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; AgaMatrix, Glytec, LLC. G.P.Forlenza: Advisory Panel; Lilly, Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. B.A.Buckingham: Advisory Panel; Arecor, Lilly Diabetes, Medtronic, Other Relationship; Insulet Corporation, Research Support; Insulet Corporation, Lilly Diabetes, Medtronic. A.B.Criego: Advisory Panel; Insulet Corporation, Other Relationship; Medscape, Sanofi, Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Medtronic. M.Schoelwer: Other Relationship; Dexcom, Inc., Research Support; Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc. S.A.Macleish: Advisory Panel; Insulet Corporation. J.Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Cecelia Health, Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Consultant; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, JDRF, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Speaker's Bureau; Lilly Diabetes. Funding Insulet Corporation

759-P: Glycemic Outcomes over 15 Months with the Omnipod 5 Automated Insulin Delivery System

Safe and effective use of the Omnipod 5 Automated Insulin Delivery (AID) System was demonstrated in adults and children with type 1 diabetes (T1D) during a 3-mo pivotal study. Longer studies evaluating durability of glycemic benefit of AID systems for &amp;gt;1 year are limited. We present results from a 12-mo extension study for a total of 15mo of system use. In the pivotal study, participants aged 6-70y with T1D≥6mo and A1C&amp;lt;10% used the AID system for 3mo, after 14d of their standard therapy (ST, pump therapy or multiple daily injections) . They were then invited to continue system use in an extension study, with outcomes measured every 3mo. Safety and efficacy endpoints included severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) , and A1C and time in range (TIR, % 70-180 mg/dL) , respectively, during each 3-mo AID interval compared with the ST phase. Most participants (95%) continued into the extension study. At baseline, children (N=110, ages 6-13.9y) and adults (N=114, ages 14-70y) were aged (mean±SD) 10±2y and 37±14y with T1D duration 5±3y and 17±11y, respectively. There were 2 SH and 1 DKA episodes during the 12-mo extension. For both age groups, TIR and A1C improvements were sustained through 15mo of system use compared with ST. The safety and improved glycemic outcomes from the 3-mo pivotal study persisted for an additional 12mo, indicating the potential long-term benefit of the Omnipod 5 System. Disclosure A.B.Criego: Advisory Panel; Insulet Corporation, Other Relationship; Medscape, Sanofi, Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Medtronic. J.Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Cecelia Health, Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Consultant; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, JDRF, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Speaker's Bureau; Lilly Diabetes. S.N.Mehta: None. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. V.Shah: Advisory Panel; Medscape, Sanofi, Consultant; Dexcom, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk. A.Bhargava: Research Support; Abbott Diabetes, AbbVie Inc., Boehringer Ingelheim International GmbH, Boston Therapeutics, Inc., Covance, Dexcom, Inc., Eli Lilly and Company, Gan &amp; Lee Pharmaceuticals, Insulet Corporation, Kowa Pharmaceuticals America, Inc., Lexicon Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Medtronic, Novo Nordisk, Poxel SA, Quintiles, Sanofi, Senseonics, Tolerion, Inc., Viking Therapeutics, vTv Therapeutics. R.S.Weinstock: Research Support; Boehringer Ingelheim International GmbH, Dexcom, Inc., Diasome, Eli Lilly and Company, Insulet Corporation, Kowa Pharmaceuticals America, Inc., Medtronic, Novo Nordisk, Tandem Diabetes Care, Inc., Tolerion, Inc. S.A.Macleish: Advisory Panel; Insulet Corporation. D.Desalvo: Consultant; Dexcom, Inc., Insulet Corporation, Research Support; Insulet Corporation. T.C.Jones: None. G.Aleppo: Consultant; Insulet Corporation, Research Support; AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Fractyl Health, Inc., Insulet Corporation, Novo Nordisk, Speaker's Bureau; Dexcom, Inc. A.L.Carlson: Advisory Panel; MannKind Corporation, Employee; Bright Health Group, Other Relationship; Medtronic, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Sanofi, UnitedHealth Group. B.A.Buckingham: Advisory Panel; Arecor, Lilly Diabetes, Medtronic, Other Relationship; Insulet Corporation, Research Support; Insulet Corporation, Lilly Diabetes, Medtronic. T.T.Ly: Employee; Insulet Corporation, Stock/Shareholder; Insulet Corporation. Omnipod 5 research group: n/a. G.P.Forlenza: Advisory Panel; Lilly, Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc. B.W.Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc. Funding This study was funded by Insulet Corporation.

1058-P: Diabetic Ketoacidosis during Pregnancy: Maternal Characteristics and Pregnancy Outcomes

Diabetic ketoacidosis (DKA) during pregnancy is an obstetric emergency associated with morbidity and mortality. As this condition is rare (affecting 1-3% pregnant women with preexisting diabetes) , available data are limited. The aim of this retrospective cohort study is to present comprehensive data on maternal characteristics and pregnancy outcomes for women with DKA who attended our center for prenatal care from 2001-21. In total 71 DKA episodes were identified in 58 women, of whom 86% (n=50) had type 1 diabetes mellitus and 83% (n=48) were White. The mean (±SD) maternal age was 28 (±7) years and diabetes duration was (±7) years. Pregnancy loss during or within 1 week of the DKA episode occurred in 17% (6 miscarriages and 4 stillbirths) . There were no maternal deaths. Women were poorly prepared for pregnancy [mean 1st trimester HbA1c 9.3 (±2.5) %]. Social stressors were present in 52% (n=30) and 24% (n=14) reported smoking. The mean gestational age at DKA was 25.4 weeks (16.3 weeks for pregnancies with fetal demise vs. 27.5 weeks for livebirths, p&amp;lt;0.001) . Insulin non-adherence was the most common precipitating factor (40%) , followed by infection (23%) , and a new diagnosis of type 1 diabetes (10%) . Pre-existing hyperemesis was associated with fetal demise (31%, n=4 vs. 3%, n=2 among livebirths; p=0.004) . The mean plasma glucose at presentation was 362 mg/dL and the β-hydroxybutyrate was 4.2 mmol/L, with 28 (39%) women requiring intensive care unit (ICU) admission. Among livebirths, the mean gestational age at delivery was 32.7 weeks with 41% (n=21) requiring emergency cesarean. Large for gestational age occurred in 29% (n=17) and 8% (n=4) had shoulder dystocia. Congenital anomaly was present in 10% (n=5) . Neonatal hypoglycemia occurred in 60% (n=29) and neonatal ICU admission was required in 52% (n=25) . In summary, pregnancies affected by DKA continue to be associated with numerous adverse pregnancy outcomes. Future work should focus on optimizing prevention strategies in high-risk women. Disclosure M.Dhanasekaran: None. S.Mohan: None. D.Erickson: None. P.Shah: None. L.M.Szymanski: None. A.Vella: Advisory Panel; Crinetics Pharmaceuticals, Inc., Rezolute, Inc., vTv Therapeutics, Zealand Pharma A/S, Other Relationship; Novo Nordisk. A.M.Egan: None. Funding National Institutes of Health (K12 HD065987/HD/NICHD)

1162-P: Clinical Characteristics and Outcomes in Patients Hospitalized with Diabetic Ketoacidosis

Background: Diabetic ketoacidosis (DKA) is an acute complication of uncontrolled diabetes that is associated with increased morbidity and mortality. Objective: We aimed to examine clinical characteristics and care outcomes for patients hospitalized for DKA. Methods: We reviewed the hospital database for patients who were admitted with DKA from 2015 to 2020 in government hospitals in Qatar. Clinical characteristics, laboratory data, the severity of DKA, complications, need for admission to the intensive care unit, length of hospital stay, time to resolution of DKA, and mortality rates were evaluated in patients with type 1 diabetes (T1DM) compared to those with type 2 diabetes (T2DM) . Results: A total of 1613 episodes of DKA in 1330 patients (39.3% with T1DM and 60.7% with T2DM) were evaluated. Non-adherence to therapy was the commonest cause (40.5%) of DKA in patients with T1DM, while infection was the commonest cause (32.9%) in those with T2DM. There was no difference in the severity of DKA, mean serum glucose, mean serum sodium, and arterial pH on presentation in both groups of patients. Both groups had poorly controlled glucose (mean HbA1c of 10.1% and 10.5% in T1DM and T2DM groups respectively) . There was no difference in the time to resolution of DKA (18 hours in the T1DM group and 20 hours in the T2DM group) . Patients with T2DM had higher rates of admission to the intensive care unit (39.1% vs. 26.9% for T1DM, p&amp;lt;0.001) , longer hospital stay (mean 5 days vs. 2 days in the T1DM group, p&amp;lt;0.001) , while patients with T1DM had higher rates of recurrent DKA (35.6% vs. 21.2% in the T2DM group, p&amp;lt;0.001) . Mortality rates were significantly higher in patients with T2DM compared to those with T1DM patients (7.6% vs. 0.95%, respectively, p&amp;lt;0.001) . Conclusion: In this cohort study, poorly controlled glucose was prevalent among patients admitted with DKA. Despite higher rates of recurrent DKA in patients with T1DM, those with T2DM had more complicated hospital course and higher mortality. Disclosure M.Eledrisi: None. S.A.Beshyah: None. M.K.Aboawon: None. H.M.Alkabbani: None. A.A.Ali: None. I.Alabdulrazzak: None. M.Elhaj: None. A.O.E.Ahmed: None. H.Alqahwachi: None. J.Daghfal: None.

Hazards of administration of benzodiazepines in patients with adaptive hyperventilation: a case rapport

IntroductionOnly three population-based observational human studies provided evidence that benzodiazepines (BZD) are associated with clinically adverse respiratory outcome. Striking was the finding that BZD drug exposure was associated with a 32% significantly increased adjusted risk of all-cause mortality, including, of note, the subgroup of individuals with no comorbidities. Causation, however, cannot be inferred in observational study design and, highly likely, recipients received BZD’s in these studies to help treating anxiety related to inter alia pre-existing respiratory symptoms.ObjectivesBased on one fatal particular case, authors of current rapport explain what can go wrong when BZD’s are given in patient with respiratory impairment.MethodsAuthors provide a model on how an increase in carbon dioxide can lead to impaired cerebral autoregulation in a person with pre-existing respiratory decompensation. Discussion of integrative metabolic and vascular physiology.ResultsCase rapport of a 18 y.o. otherwise healthy man, who was hospitalized with a novel episode of diabetic ketoacidosis accompanied by profound hypocapnia and anxiety, and who deteriorated and died shortly after airway management because of a clinically important acid-base balance disturbance caused by increased carbon dioxide. All the blood tests and results of respiratory monitoring were collected and carefully assessed.ConclusionsCurrent case suggests that the P(CO(2))--HCO(3) hypothesis is consistent with known data on impaired cerebral autoregulation in diabetic ketoacidosis, driven mainly by increased levels of pCO2. In our opinion, it indicates the recommendation not to administrate BZD’s in patients with pre-existing compensatory hyperventilation as it may counter to the logic of adaptive physiology.DisclosureNo significant relationships.

Diabetic ketoacidosis: a canary in the mine for mental health disorders?

Recurrent diabetic ketoacidosis (DKA) has been linked to mental health disorders, but less is known about single DKA episodes. Most studies are retrospective, lacking control groups. To prospectively examine psychosocial factors in patients presenting with recurrent or single episode DKA and compare with people who have not had DKA. Case-controlled study (consecutive adult DKA admissions April 2015 to December 2016) at Western Health, Melbourne. Data were prospectively collected regarding diagnosed mental health disorders, likely depression (Patient Health Questionnaire (PHQ-9)), diabetes distress (Problem Areas in Diabetes (PAID) questionnaire) and presence of adverse social factors. A control group without a history of DKA was also recruited. Of 123 patients admitted with DKA (164 consecutive episodes), 70 consented to participate and 73 age-matched Type 1 diabetes controls were recruited. Eleven (61%) of 18 with recurrent DKA had a diagnosed mental health disorder versus 8 (19%) of 42 in the single episode group (P = 0.016). The prevalence of likely depression using PHQ-9 was: recurrent 50%; single 40%; and controls 22% (recurrent vs controls, P = 0.036; single vs controls, P = 0.053). Severe diabetes distress (PAID) was present in 47% of recurrent and 34% of single episode DKA (P = 0.387). As a group, DKA patients had significantly more unemployment, illicit drug use and tobacco smoking, a lower level of formal education and less regular medical contact compared with controls. Mental health disorders and adverse socioeconomic factors appear to be common in patients with DKA. The diagnosis of DKA presents an excellent opportunity to screen for depression and offer appropriate intervention.

Risk factors, outcomes, and predictors of resolution of acute kidney injury in children with diabetic ketoacidosis.

Acute kidney injury (AKI) is a common complication in patients with diabetic ketoacidosis (DKA) (incidence 35-77%). AKI evolution during DKA treatment/recovery is poorly understood. Our aim was to assess children with DKA for prevalence, short-term kidney outcomes, severity, and predictors of AKI development and resolution. This retrospective cohort study included children aged 2-14years admitted with DKA between January 2016 and May 2020 in a Saudi tertiary care hospital. We defined AKI as an increase in serum creatinine of > 1.5 times baseline or > 3mg/dL (26mmol/L) within 48h. Of 213 patients admitted with DKA, 172 (80.75%) developed AKI: stage 1 in 83 (38.96%), stage 2 in 86 (40.37%), and stage 3 in 3 (1.4%). No patient required dialysis. Multivariate analysis showed an increased risk of developing AKI with male gender (OR = 2.85) and lower serum bicarbonate (OR = 0.83) when adjusted for initial heart rate, hematocrit, new onset diabetes, and recurrent AKI. The mean time to AKI resolution was 13.21 ± 6.78h. Factors leading to prolonged recovery from AKI in linear regression analysis were older age (B coefficient = 0.44, p = 0.01), recurrent DKA episodes (B coefficient = 3.70, p value 0.003), increased acidosis severity (B coefficient = - 0.44, p = 0.04), increased time to anion gap normalization (B coefficient = 0.44, p = 0.019), and increased initial glucose (B coefficient = 0.01, p = 0.011). In our cohort, AKI is a common, but mostly transient complication in children presenting with DKA, and its severity is associated with longer intensive care stays and time for acidosis resolution. AKI was associated with male gender, and lower serum bicarbonate. Proper consideration of such risk factors is needed for AKI assessment and management in future DKA clinical practice guidelines. A higher resolution version of the Graphical abstract is available as Supplementary information.

Closed-Loop Insulin Pump Therapy in Young Type 1 Diabetic Children

Source: Ware J, Allen JM, Boughton CK, et al. Randomized trial of closed-loop control in very young children with type 1 diabetes. N Engl J Med. 2022;386:209-219; doi: 10.1056/NEJMoa2111673Investigators from multiple institutions conducted a crossover randomized trial to compare the effectiveness and safety of a closed-loop system (ie, artificial pancreas) to sensor-augmented insulin pump therapy in young children with type 1 diabetes. Participants were children 1-7 years old with a diagnosis of type 1 diabetes for at least 6 months, recruited from diabetes centers in 4 European countries. The closed-loop system consisted of a continuous glucose sensor and insulin pump connected to a smartphone app. The app included an algorithm that automatically adjusted insulin delivery based on real-time sensor glucose readings. With the sensor-augmented pump, insulin therapy was stopped if an algorithm predicted that sensor glucose levels were likely to drop below a specified threshold. Study children were randomized to receive 16 weeks of treatment with the closed loop system, followed by 16 weeks using the augmented-sensor pump, or vice versa. The primary outcome was percentage of time spent in the target glucose range (70 to 170 mg/dL) during each treatment period. Secondary outcomes included percentage of time spent in a hyperglycemic range (>180 mg/dL) and hypoglycemic range (<70 mg/dL) and mean glucose levels. These outcomes were based on readings from the glucose sensors. Glycated hemoglobin levels were measured at baseline and at the end of each treatment period. Differences in outcomes between the closed-loop and sensor-augmented pump treatment period were assessed with repeated-measures linear regression models. Data on adverse events also were collected.Data were analyzed on 74 children with a mean age of 5.6 ±1.6 years. The mean glycated hemoglobin level at baseline was 7.3 ±0.7%. The mean time spent in the target glucose range were 71.6 ±5.9% during the closed-loop period and 62.9 ±9.0% in the sensor-augmented pump period (adjusted difference, 8.7 percentage points; 95% CI, 7.4, 9.9; P <0.001). The median time spent at glucose level >180 mg/dL was significantly less during the closed-loop period than during the control period (22.9% vs 31.7%; adjusted difference, -8.5 percentage points; 95% CI, -.9.9, -7.1; P <0.001); mean sensor glucose levels (145 ±11.8 mg/dL and 158.1 ±18.5 mg/dL, respectively; P <0.001) and mean glycated hemoglobin levels (6.6 ±0.6% and 7.0 ±0.7%) were significantly lower during the closed-loop period than during treatment with the segmented-sensor pump. There was no difference between treatment periods for percentage of time with glucose <70 mg/dL (P = 0.74). One participant had a serious adverse event (severe hypoglycemia) during their closed-loop treatment period.The authors conclude that a closed-loop system improved glycemic control in young children with type 1 diabetes.Dr Fechner has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Type 1 diabetes is very difficult to manage in the young child. The therapeutic window for insulin is very narrow, with too much insulin resulting in hypoglycemia and too little insulin resulting in hyperglycemia. The last 5 years have seen tremendous advances in the technology available to children with type 1 diabetes. A 2019 study comparing the insulin pump to multiple daily injections showed that the insulin pump was superior to multiple daily injections. (See AAP Grand Rounds. 2019;42[1]:4.) Continuous glucose monitoring has decreased parental anxiety regarding risk of hypoglycemia and diabetic ketoacidosis;1 however, parents still are responsible for making insulin dose adjustments, and glycemic control overall is not improved.2 The results of a 2020 study of 6- to 13-year-olds with type 1 diabetes demonstrated that glucose levels were in the target range for a longer period of time in those randomized to a closed-loop system than those using a sensor-augmented pump. (See AAP Grand Rounds. 2020;44[6]:69.)3 The current researchers compared a hybrid closed-loop insulin delivery system to sensor-augmented pump therapy in younger children with type I diabetes.The strengths of the current study are the randomized, crossover design using the same algorithm with the closed-loop functionality either abled or disabled; each therapy was 16 weeks, which allowed a meaningful glycated hemoglobin to be obtained. There were no restrictions on previous episodes of hypoglycemia and diabetic ketoacidosis, and the study included a very young children with diabetes, who are more vulnerable to hypo- and hyperglycemia. Weaknesses of this study include underrepresentation of ethnic minorities and a patient population not representative of the typical type 1 diabetes population, as the average glycated hemoglobin level was 7.3% at baseline.4 Decreased patient compliance outside of the confines of a study may be reflected in poorer glucose control regardless of the insulin delivery system used.Hybrid closed-loop insulin therapy in young children with type 1 diabetes has the potential to significantly improve long-term outcomes through improved glycemic control.