Severe Diabetic Ketoacidosis Research Articles

The effect of war and siege on children with diabetes admitted to ayder comprehensive specialized hospital in mekelle, tigray, ethiopia: a cross-sectional study

The armed conflict in Tigray, which spanned from November 2020 to November 2022, along with the accompanying siege, led to the near-total collapse of Tigray’s healthcare system. Type 1 Diabetes Mellitus, the most common chronic condition in children, requires significant lifestyle adjustments, including daily insulin injections, regular glucose monitoring, and dietary modifications; all of which are severely impacted by war and siege. This study compared Type 1 diabetes care for children at the Ayder Comprehensive Specialized Hospital, Tigray, during the conflict and siege period with that of the pre-war period. We conducted a retrospective cross-sectional survey, analyzing data from September 2019 to August 2020 (pre-war period) and comparing it with data from September 2021 to August 2022 (war and siege period). Descriptive statistics, including frequencies and percentages, were employed, and Pearson’s or Spearman’s correlation analyses were used to evaluate correlations where appropriate. We identified 143 pediatric patients admitted (56 during the pre-war period and 87 during the war and siege period), with a mean age of 109 months in both periods. During the war and siege, a higher proportion of diabetes admissions were due to diabetic ketoacidosis (DKA) (90%) compared to the pre-war period (75%). In the pre-war period, the most common trigger for DKA was infections (35%), while in the war and siege period, it shifted to malnutrition (47%), infections (46%), lack of access to healthcare facilities (31%), and running out of medicines (24%). Complications such as death, renal failure, cerebral edema, and shock were more prevalent during the war and siege periods. The case fatality rate was significantly higher during the war and siege (9%) compared to the pre-war period (0%), correlating strongly with the severity of DKA, the degree of hypokalemia, the presence of complications, and admission during the war and siege. Our study showed the negative impact of war and siege on diabetes care in children demonstrating a high rate of DKA admissions with increased severity, complications, malnutrition, and case fatality rates. People with diabetes especially type 1 deserve great attention during such a crisis as the lack of insulin could lead to severe complications including death.

Two- versus one-bag fluid delivery in pediatric and adolescent diabetic ketoacidosis: a systematic review and meta-analysis.

Two rehydration protocols currently exist to treat diabetic ketoacidosis (DKA) in pediatric patients aged <21 years: the traditional "one-bag" system and the more recent "two-bag" system. This study aimed to evaluate the safety and efficacy of the newer two-bag system versus the well-established one-bag system. The CiNAHL, Cochrane Library, Embase, PubMed, Scopus, and Web of Science databases were comprehensively searched from inception to June 2023 by 2 independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis framework. Eligible studies were those that reported participants <21 years of age who presented to the emergency room with a clinical diagnosis of DKA. This review was prospectively registered on PROSPERO (CRD42023427551). From the initial screening of 42 studies, 8 unique studies encompassing 583 patients met the eligibility criteria. The analysis yielded no significant intergroup differences in hypoglycemia (odds ratio, 0.61; 95% confidence interval [CI], 0.20-1.87; I2=3%) or mean glucose correction rate (mean difference [MD], 0.04 mg/ dL/hr; 95% CI, -13.10 to 13.17; I2=64%). The incidence of cerebral edema was as low (0.17%) across groups, with only one case reported in the one-bag group. Notably, the mean time to DKA resolution (MD, -3.24 h; 95% CI, -5.57 to -0.91; I2=0%) and mean response time for intravenous fluid changes (MD, -32.75 min; 95% CI, -43.21 to -22.29; I2=59%) was lower for the two-bag system. This meta- analysis presents preliminary evidence suggesting that the two-bag system may confer advantages over the one-bag system for selected patients. However, further studies with greater patient stratification based on DKA severity, fluid composition, and protocol are needed to draw definitive conclusions and elucidate the extent of these advantages.

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

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

12469 Impact Of Covid-19 Infection On Diabetic Ketoacidosis Severity And Outcomes In Adult Population- A Retrospective Observational Study

Abstract Disclosure: E.M. Niedzialkowska: None. K. Childers: None. L. Qu: None. L. Misra: None. M.R. Brennan: Consulting Fee; Self; Insulet Corporation, Bayer, Inc., Novo Nordisk. Background: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM) that can be precipitated by SARS-CoV2 infection. We analyzed clinical and demographic characteristics of patients admitted with DKA to investigate if SARS-CoV2 infection affects DKA severity on admission and outcomes. Methods: We conducted a retrospective cohort study that included adult patients admitted with a diagnosis of DKA between March 1, 2020, and March 1, 2023. Patients' demographic data including age, sex, race, ethnicity, laboratory test results on admission, ICU admissions and length of hospital stay (LOS) were compared. Patient characteristics and outcomes of interest were stratified by COVID-19 test results and compared using the Kruskal-Wallis test for continuous variables and Fisher’s exact test for categorical variables. DKA severity was classified based on HCO3 values: mild 15-18 mEq/L, moderate 10-14 mEq/L, severe &amp;lt;10 mEq/L. Results: The study included 902 patients, of which 734 tested negative (COVID-) and 168 tested positive (COVID+) for SARS-CoV2. The mean age was significantly higher (54.09) in COVID-19+ group compared to COVID-19- group (48.25) (p&amp;lt;0.001). The cohort included 49.1% females, 51.7% Whites, 43.3% Blacks, 89.8% Non-Hispanic/Latino, 2.7% Hispanic/Latino. We did not find statistically significant differences in sex (p= 0.608), race (p =0.277), ethnicity (p=0.072) anion gap (p=0.783), glucose (p=0.140), hemoglobin a1c (ha1c) values on admission (p=0.876) and ICU admissions (p=0.266) between both groups. The majority (55.3%) of the patients presented with severe DKA, followed by moderate DKA in 26.6% and mild disease in 18.1% of patients without statistically significant differences between groups (p= 0.128). The mean LOS in COVID + group (11.94 days) was longer than COVID- (6.85) group (p&amp;lt;0.001). Mean venous pH was significantly lower in COVID-19- (7.14) compared to COVID+ (7.17) group (p= 0.016). Betahydroxybutyrate (BHB) levels on admission were higher in COVID- group (7.98 mmol/L, N 0.02-0.27 mmol/L) compared to COVID + (7.10mmol/L) cohort. Conclusion: Patients diagnosed with COVID-19 and DKA on admission did not present with more severe disease compared to patients that tested negative. COVID+ patients were older (54.09 vs 48.2) and had significantly longer LOS (11.94 vs 6.85 days). We did not identify statistically significant differences between race, ethnicity, sex, glucose, anion gap, Ha1c on admission and ICU admission rate. BHB levels on admission were higher in patients that tested negative. Interestingly, mean pH was higher in COVID-19 positive group possibly due to respiratory disorders. Presentation: 6/1/2024

8503 Analyzing Prescription Practices for Back-up Insulin and Glucagon in Type 1 Diabetes Patients Using Insulin Pumps: Findings From Cleveland Clinic

Abstract Disclosure: A. Iqbal: None. J. Ambalavanan: None. K. Alkwatli: None. P.P. Rao: None. Background: It is estimated that about 400,000 patients with type 1 diabetes (T1D) in the U.S. are using insulin pumps1. This number has been steadily increasing with expanding insurance coverage and newer, more convenient, user-friendly technology. Though these devices remarkably improve patients’ glycemic control, failure of these pumps, due to reasons such as clogging or kinking of tubing, air bubbles, pump display issues, site reaction/infection, is a frequently encountered problem. During these events, having a backup plan in the form of injectable insulin is essential to prevent severe hyperglycemia and diabetic ketoacidosis (DKA). Increasing insulin pump use also predisposes patients to severe hypoglycemia. In these cases, at-home glucagon administration can be lifesaving. Methods: Using the EPIC Cogito extracts and reporting service, data was extracted for adult patients seen at the Cleveland Clinic main campus between January 1, 2021, to January 1, 2023, using ICD codes for T1D and insulin pump status. Data collected included age, sex, prescription status for basal insulin, type of basal insulin, glucagon prescription, and current medication list.ResultsWe were able to analyze 86 patients (67% females, n=58; 33% male, n=28) with T1D utilizing an insulin pump. The average age was 48.6+18.18 years. Of the 86 patients, 51 (59%) had prescriptions for long-acting backup insulin. Only 21 patients (24%) had a prescription for glucagon. Discussion: Insulin pump failure is one of the most common causes of DKA in patients with T1D2. Educating patients on the use of long-acting injectable insulin in the event of pump failure and ensuring active prescription for every patient using an insulin pump at each visit can decrease the risk of DKA and prevent hospitalizations. Similarly, the use of a continuous subcutaneous insulin infusion (CSII) puts patients at high risk of hypoglycemia. Per Standards of Care in Diabetes 2024, glucagon should be prescribed in all patients using insulin3. Our analysis reveals that the practice of prescribing backup insulin and glucagon at Cleveland Clinic Institute needs significant improvement to potentially prevent DKA and severe hypoglycemia requiring hospitalization.

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

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

12201 Ketogenic-diet As A Trigger Of First Episode Diabetic Ketoacidosis In A Woman Living With Type 1 Diabetes Mellitus

Abstract Disclosure: M.E. Chacon Cruz: None. A.N. Gonzalez Bossolo: None. G.J. Mora Osoria: None. A number of dietary patterns have been proposed as an effective method for weight reduction. A keto diet is a strict low-carbohydrate and high-fat diet. The reduction in carbohydrates enables the body to rely on fat as a predominant energy source leading to a state of ketosis. However, a serious but rare complication of the ketogenic diet is ketoacidosis associated with low carbohydrate intake, which should be cautiously monitored in people with a predisposition to the condition, such patient with diabetes mellitus type 1. We report the case of a female patient living with type 1 diabetes mellitus female who developed her first episodes of diabetic ketoacidosis (DKA) as the following the course of ketogenic diet. A 53 y/o Female patient with past medical history diabetes mellitus type 1 and pernicious anemia went emergency department complaining pelvic pain associated with weakness, nausea and vomiting for about 1 day of evolution. Patient also refers that during the past 2 weeks she has been doing a detox and taking some herbal and tea. Other physical examinations were unremarkable except for moderate dehydration. The initial testing revealed patients meet criteria for severe diabetes ketoacidosis (DKA) with a pH: 7.04, CO2 15, serum central bicarbonate in 6 mmol/L and elevated blood glucose in 504 mg/dl and positive urine and serum ketones, C-Peptide less than 0.02 ng/ml. and glycosylated hemoglobin in 8.25%. She was admitted to the intensive care unit and treated with intravenous saline, intravenous insulin infusion, and electrolyte repletion. Blood glucose levels and metabolic acidosis improved. After DKA resolved patient refers that week started with Keto-diet and was restricting carbohydrates. Patient was discharge home with multiple injection insulin and followed by Endocrinologist services in the external clinic for a follow up. This case illustrates the challenges and the importance of dietary history providing clues to the diagnosis. If we had never asked her about her diet, we would not have found the reason that brought her to the DKA. This case demonstrates the development of DKA following ketogenic diet in a patient with type 1 diabetes. It is important for physicians to be aware of this rare potential complication of ketogenic diet which is infrequently reported in literature. Therefore, physicians should be cognizant of the complications and risks, and benefits of the ketogenic diet. Risks and benefits of the ketogenic diet should be discussed with patients before initiation of this diet. The patient was followed in an outpatient clinic with Endocrinologist service for evaluation for an insulin pump. Presentation: 6/1/2024

Characteristics and Treatment Outcome of Pediatric Diabetic Ketoacidosis in Mekong Delta, Vietnam: A 5-Year Retrospective Study

Background Diabetic ketoacidosis (DKA), a critical and potentially fatal complication resulting from a lack of insulin, presents with elevated blood sugar, acid-base imbalance, and increased ketone bodies. Objectives Our research was designed to assess the clinical manifestations, laboratory findings, and outcomes of treatment in children diagnosed with DKA over a span of five years in the Mekong Delta region of Vietnam. Methods This study retrospectively analyzed pediatric cases of diabetic ketoacidosis treated at a major pediatric center in the Mekong Delta between 2017 and 2021. Results Diabetic ketoacidosis was more common in older children aged 11 – 16 years (66.7%), and females (70%). The majority of cases had not been diagnosed with previous diabetes (60%) and no history of diabetic ketoacidosis (90%). In univariate analysis, female gender (OR, 13.0; 95% CI, 1.4 – 124.3; p=0.026), previous diabetes diagnosis (OR, 7.8; 95% CI, 1.5 – 41.2; p=0.016), precipitating factors (OR, 10.1; 95% CI, 1.1 – 97.0; p=0.045), tachypnea (OR, 5.5; 95% CI, 1.1 – 26.4; p=0.033), Kussmaul breathing (OR, 5.4; 95% CI, 1.1 – 26.0; p=0.036), serum potassium level (OR, 3.5; 95% CI, 1.2 – 10.4; p=0.027), and anion gap (OR, 1.6; 95% CI, 1.8 – 2.3; p=0.003) were associated factors with severe DKA. All cases in our study had a 100% survival rate. Anion gap was an independent factor associated with severe diabetic ketoacidosis after adjustment multivariate analysis. Conclusion: Female, younger age, precipitating factors, tachypnea, Kussmaul’s breathing, and relevant laboratory findings, including increased anion gap, should be considered to ensure successful management in pediatric diabetic ketoacidosis. Bangladesh Journal of Medical Science Vol. 23 No. 04 October’24 Page : 1112-1119

Comparison of the Volumetric Parameters of Platelets in Diabetic Children with and without Diabetic Ketoacidosis: A Case-Control Study in the North of Iran

Background: This study aimed to determine the volumetric parameters of platelets including MPV (Mean Platelet Volume) and PDW (Platelet Distribution Width) in diabetic children with and without diabetic ketoacidosis (DKA) and to evaluate their relationship with the severity of DKA. Materials and Methods: A case-control study was conducted on 112 children with type 1 diabetes mellitus (T1DM), with and without DKA, who referred to Amirkola Children's Hospital, Iran, in 2016-2021. Of them, 43 were boys, and 69 were girls. The diagnosis of diabetes was based on clinical symptoms and diagnostic criteria, and DKA was diagnosed through the analysis of arterial blood gas. The patients’ MPV and PDW were also evaluated, and the P values less than 0.05 were considered significant. Results: Out of 112 children with diabetes (with the mean age of 8.71 ± 3.22 years), 56 persons had DKA. In terms of DKA severity, 17 patients (30.4%) had mild, 29 (51.8%) had moderate, and 10 (17.8%) had severe DKA. The children with DKA had the mean blood glucose of 490.98±46.11mg/dL, MPV of 10.02± 1.19fl), and PDW of 13.07± 1.18flwere significantly higher (P&lt;0.001). It was found that, an increase in the severity of DKA would raise the mean MPV (P = 0.006) and PDW(P&lt;0.001) significantly. Conclusion: Based on the results of this study, as the severity of DKA increases in diabetic children, the mean levels of MPV and PDW increase significantly. Therefore, it is suggested that MPV and PDW be used to predict the severity of DKA in diabetic children.

Factors associated with severe diabetic ketoacidosis in patients diagnosed with type 1 diabetes: a decade-long cross-sectional analysis.

The aim of this study was to identify factors associated with severe diabetic ketoacidosis (DKA) at the onset of type 1 diabetes mellitus (T1DM) in adult patients. We conducted a retrospective analysis over a 10-year period including adults newly diagnosed with T1DM. Eligible participants were diagnosed with DKA at the time of T1DM diagnosis. DKA severity was categorized as mild, moderate, or severe. Data were collected on age, body mass index, family history of diabetes and autoimmune disorders, lifestyle habits, delayed diagnosis, and preceding factors. A total of 305 participants (69.8% men) with T1DM were included. Overall, 63 patients were admitted with severe DKA (Group 1) and 242 with non-severe DKA (Group 2). Factors associated with severe DKA at diagnosis of T1DM were a long period between symptom onset and first hospitalization, preceding infection, tachypnea, thrombocytopenia, anemia, hepatic cytolysis, polyuria, and tachycardia. The present findings highlight the need for improving awareness about diabetes symptoms among physicians and the public to reduce the occurrence and severity of DKA at the onset of T1DM.

GLP-1 receptor agonist-induced diabetic ketoacidosis: A case report.

Glucagon-like peptide-1 is an endogenous incretin that plays an active role in weight loss and hypoglycemia. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), which has been approved for the treatment of patients with type 2 diabetes (T2D). GLP-1RAs can increase insulin secretion and inhibit glucagon release, thereby leading to a decrease in blood glucose levels within the body. Specifically, GLP-1RAs control postprandial blood glucose levels by inhibiting hepatic glucose production and delaying gastric emptying. However, attention should be given to gastrointestinal adverse reactions. There are currently a few cases of GLP-1RA causing diabetic ketoacidosis (DKA). The following report details the case of a 50-year-old Chinese female who has been living with diabetes for 12 years. Initially diagnosed with T2D, she was subsequently identified as a patient with latent autoimmune diabetes in adults (LADA) following treatment. The patient presented severe nausea, vomiting, and fatigue 1 day after injecting dulaglutide 1 time and discontinuing insulin therapy. She was diagnosed with severe DKA in the emergency department. LADA and DKA. Changed from dulaglutide to insulin therapy. After discontinuing dulaglutide and switching to insulin for blood glucose reduction, the patient's DKA was corrected, and blood glucose levels returned to normal. This case suggests that clinicians should be alert to patients with severe DKA in cases of severe gastrointestinal adverse reactions after the use of GLP-1RAs. In addition, in most countries, GLP-1RAs are administered to patients with T2D, but we should consider the use of GLP-1RAs in patients with type 1 diabetes and LADA.

Advanced Hybrid Closed-Loop Therapy Compared With Standard Insulin Therapy Intrapartum and Early Postpartum in Women With Type 1 Diabetes: A Secondary Observational Analysis From the CRISTAL Randomized Controlled Trial.

To determine efficacy and safety of intrapartum and early postpartum advanced hybrid closed-loop (AHCL) therapy compared with standard insulin therapy in pregnant women with type 1 diabetes (T1D). CRISTAL was a double-arm, open-label, randomized controlled trial performed in Belgium and the Netherlands that assigned 95 pregnant participants with T1D 1:1 to a MiniMed 780G AHCL system (n = 46) or standard insulin therapy (n = 49). This prespecified, secondary observational analysis focused on differences in glycemic control and safety outcomes between participants from the original AHCL group who continued AHCL intrapartum (n = 27) and/or early postpartum (n = 37, until hospital discharge) and those from the original standard insulin therapy group using standard insulin therapy intrapartum (n = 45) and/or early postpartum (n = 34). Of the 43 and 46 participants in the AHCL and standard insulin therapy groups, respectively, completing the trial, 27 (62.8%) in the AHCL group continued AHCL and 45 in the standard insulin therapy group (97.8%) continued standard insulin therapy intrapartum. Compared with standard insulin therapy, intrapartum AHCL was associated with more time in range 3.5-7.8 mmol/L (71.5 ± 17.7% vs. 63.1 ± 17.0%, P = 0.030) and numerically lower time above range >7.8 mmol/L (27.3 ± 17.4% vs. 35.3 ± 17.5%, P = 0.054), without increases in time below range <3.5 mmol/L (1.1 ± 2.4% vs. 1.5 ± 2.3%, P = 0.146). Early postpartum, 37 (86.0%) participants randomized to AHCL continued AHCL, with a median increase in insulin-to-carbohydrate ratios of 67% (interquartile range -14 to 126). Similar tight glycemic control (3.9-10.0 mmol/L: 86.8 ± 6.7% vs. 83.8 ± 8.1%, P = 0.124) was observed with AHCL versus standard insulin therapy. No severe hypoglycemia or diabetic ketoacidosis was reported in either group. AHCL is effective in maintaining tight glycemic control intrapartum and early postpartum and can be safely continued during periods of rapidly changing insulin requirements.

Automated Insulin Delivery for Young People with Type 1 Diabetes and Elevated A1c

BackgroundAutomated insulin delivery is the treatment of choice in adults with type 1 diabetes. Data are needed on the efficacy and safety of automated insulin delivery for children and youth with diabetes and elevated glycated hemoglobin levels.MethodsIn this multicenter, open-label randomized controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio either to use an automated insulin delivery system (MiniMed 780G) or to receive usual diabetes care of multiple daily injections or non-automated pump therapy (control). The patients were children and youth (defined as 7 to 25 years of age) with elevated glycemia (glycated hemoglobin ≥8.5% with no upper limit). The primary outcome was the baseline-adjusted between-group difference in glycated hemoglobin at 13 weeks.ResultsA total of 80 patients underwent randomization (37 to automated insulin delivery and 43 to control) and all patients completed the trial. At 13 weeks, the mean (±SD) glycated hemoglobin decreased from 10.5±1.9% to 8.1±1.8% in the automated insulin delivery group but remained relatively consistent in the control group, changing from 10.4±1.6% to 10.6±1.8% (baseline-adjusted between-group difference, −2.5 percentage points; 95% confidence interval [CI], −3.1 to −1.8; P<0.001). Patients in the automated insulin delivery group spent on average 8.4 hours more in the target glucose range of 70 to 180 mg/dl than those in the control group. One severe hypoglycemia event and two diabetic ketoacidosis events occurred in the control group, with no such events in the automated insulin delivery group.ConclusionsIn this trial of 80 children and youth with elevated glycated hemoglobin, automated insulin delivery significantly reduced glycated hemoglobin compared with usual diabetes care, without resulting in severe hypoglycemia or diabetic ketoacidosis events. (Funded by Lions Clubs New Zealand District 202F and others; Australian New Zealand Clinical Trials Registry number, ACTRN12622001454763.)

The DPP-4 inhibitor sitagliptin improves glycaemic control and early-stage diabetic nephropathy in adolescents with type 1 diabetes using the MiniMed 780G advanced hybrid closed-loop system: a randomised controlled trial.

Dipeptidyl peptidase-4 (DPP-4) inhibition has beneficial effects on various metabolic indicators in diabetes. Stromal cell-derived factor-1 (SDF-1) is expressed in diverse organs including the kidneys and is cleaved and inactivated by DPP-4 enzyme. The aim of this study was to conduct a randomised controlled trial to assess the effect of sitagliptin on diabetic nephropathy when used as an add-on therapy to the advanced hybrid closed-loop (AHCL) system in adolescents with type 1 diabetes and nephropathy. This open-label, parallel-group, randomised controlled trial took place at the Pediatric Diabetes Clinic, Ain Shams University, Egypt. Forty-six adolescents aged 14.13 ± 2.43 years on the MiniMed 780G system for at least 6 months before study, with HbA1c ≤69 mmol/mol (8.5%) and diabetic nephropathy in the form of microalbuminuria, were randomly assigned to two groups (n=23 for each) based on a computer-generated randomisation sequence. The intervention group received oral sitagliptin 50 mg for 3 months. The other group used AHCL only and served as a control group. The primary outcome measure was the change in urinary albumin/creatinine ratio (UACR) after 3 months of administration of sitagliptin. The key secondary outcome measure was the change from baseline in SDF-1 levels after treatment. Data for all participants were analysed. No significant difference was found between the groups as regards baseline clinical and laboratory characteristics as well as AHCL system settings (p>0.05). Serum SDF-1 levels were higher in all individuals with type 1 diabetes vs healthy control individuals (p<0.001). After 3 months, sitagliptin resulted in a significant decrease of SDF-1 levels from 3.58 ± 0.73 to 1.99 ± 0.76 ng/ml (p<0.001), together with improvement of UACR from 7.27 ± 2.41 to 1.32 ± 0.31 mg/mmol (p<0.001). In addition, sitagliptin reduced postprandial glucose, sensor glucose, coefficient of variation and total daily dose of insulin, while time in range 3.9-10.0 mmol/l (70-180 mg/dl) and insulin-to-carbohydrate ratio were significantly increased. Sitagliptin was safe and well-tolerated without severe hypoglycaemia or diabetic ketoacidosis. Sitagliptin as an add-on therapy to AHCL had a reno-protective effect for individuals with type 1 diabetes and diabetic nephropathy, in addition to the improvement of time in range while reducing glycaemic variability and without compromising safety. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. ClinicalTrials.gov NCT06115460.

Deciphering the role of lactate as aprognostic indicator in pediatric diabetic ketoacidosis.

Serum lactate levels have been recognized as arobust marker for predicting disease severity and survival in many critically ill children but consensus is lacking regarding its utility in diabetic ketoacidosis. This study aimed to investigate the relationship between initial lactate levels and disease severity in pediatric patients presenting with diabetic ketoacidosis. This single-center retrospective descriptive study involved pediatric patients with diabetic ketoacidosis in the pediatric emergency department between January 2022 and April 2023. Patients were diagnosed using the International Society for Pediatric and Adolescent Diabetes 2022 guidelines. Among the 112 patients included in the study, 41 (36.6%) were classified as mild, 42 (34.8%) as moderate and 32 (28.6%) as severe acidosis. Astatistically significant difference was observed between the time to resolution and clinical severity of diabetic ketoacidosis (p < 0.001). Elevated lactate levels of 2.5 mmol/L or above were detected in 37.5% (42/112) of our patients and asignificant increase in clinical severity was observed as lactate levels increased (p < 0.001). Correlation analysis revealed no significant relationship between lactate levels and time to resolution of diabetic ketoacidosis or length of intensive care unit stay. Multivariate analysis demonstrated asignificant association between lactate levels and severity of acidosis (p: 0.046). Although there is an association between the severity of acidosis and lactate levels in diabetic ketoacidosis, contrary to expectations, this relationship was not found to be associated with adverse outcomes. An important point not to be overlooked by pediatricians is that elevated lactate levels in diabetic ketoacidosis may not always herald poor outcomes.

Safety of Options to "Boost" (Enhancing Insulin Infusion Rates) and "Ease-Off" (Reducing Insulin Infusion Rates) in CamAPS FX Hybrid Closed-Loop System: A Real-World Analysis.

The usage and safety of the Boost and Ease-off features in the CamAPS FX hybrid closed-loop system were analyzed in a retrospective analysis of real-world data from 7,464 users over a 12-month period. Boost was used more frequently than Ease-off, but for a shorter duration per use. Mean starting glucose was above range for Boost (229 ± 51 mg/dL), and within range for Ease-off (114 ± 29 mg/dL). Time spent below 70 mg/dL was low during Boost periods [median (interquartile range; IQR) 0.0% (0.0, 0.5%)], and lower than during no Boost periods [2.1% (1.2, 3.4%)], while time spent above 180 mg/dL was lower during Ease-off periods (15 ± 14%) compared with no Ease-off periods (25 ± 12%). There were no episodes of severe hypoglycemia or diabetic ketoacidosis attributed to Boost or Ease-off use. Boost and Ease-off allow users to engage safely with CamAPS FX to manage their glucose levels during periods of more-than-usual and less-than-usual insulin needs.

Efficacy and Safety of Different Hybrid Closed Loop Systems for Automated Insulin Delivery in People With Type 1 Diabetes: A Systematic Review and Network Meta-Analysis.

To compare the efficacy and safety of different hybrid closed loop (HCL) systems in people with diabetes through a network meta-analysis. We searched MEDLINE, EMBASE, CENTRAL and PubMed for randomised clinical trials (RCTs) enrolling children, adolescents and/or adults with type 1 or type 2 diabetes, evaluating Minimed 670G, Minimed 780G, Control-IQ, CamAPS Fx, DBLG-1, DBLHU, and Omnipod 5 HCL systems against other types of insulin therapy, and reporting time in target range (TIR) as outcome. A total of 28 RCTs, all enrolling people with type 1 diabetes, were included. HCL systems significantly increased TIR compared with subcutaneous insulin therapy without continuous glucose monitoring (SIT). Minimed 780G achieved the highest TIR ahead of Control IQ (mean difference (MD) 5.1%, 95% confidence interval (95% CI) [0.68; 9.52], low certainty), Minimed 670G (MD 7.48%, 95% CI [4.27; 10.7], moderate certainty), CamAPS Fx (MD 8.94%, 95% CI [4.35; 13.54], low certainty), and DBLG1 (MD 10.69%, 95% CI [5.73; 15.65], low certainty). All HCL systems decreased time below target range, with DBLG1 (MD -3.69%, 95% CI [-5.2; -2.19], high certainty), Minimed 670G (MD -2.9%, 95% CI [-3.77; -2.04], moderate certainty) and Minimed 780G (MD -2.79%, 95% CI [-3.94; -1.64], high certainty) exhibiting the largest reductions compared to SIT. The risk of severe hypoglycaemia and diabetic ketoacidosis was similar to other types of insulin therapy. We show a hierarchy of efficacy among the different HCL systems in people with type 1 diabetes, thus providing support to clinical decision-making. PROSPERO CRD42023453717.

Continuous glucose monitoring for self-management of diabetes in people living with type 2 diabetes mellitus on basal insulin therapy: A microsimulation model and cost-effectiveness analysis from a US perspective with relevance to Medicaid.

Reducing the risks of complications is a primary goal of diabetes management, with effective glycemic control a key factor. Glucose monitoring using continuous glucose monitoring (CGM) technology is an important part of diabetes self-management, helping patients reach and maintain targeted glucose and glycated hemoglobin (HbA1c) levels. Although clinical guidelines recommended CGM use, coverage by Medicaid is limited, likely because of cost concerns. To assess the cost-effectiveness of FreeStyle Libre CGM systems, compared with capillary-based self-monitoring of blood glucose (SMBG), in US individuals with type 2 diabetes mellitus using basal insulin. A patient-level microsimulation model was used to compare CGM with SMBG for a population of 10,000 patients. A 10-year horizon was used, with an annual discount rate of 3.0% for costs and utilities. Model population characteristics were based on US national epidemiology data. Patient outcomes were based on published clinical trials and real-world studies. Annual costs, reflective of 2023 values, included CGM and SMBG acquisition costs and the costs of treating diabetic ketoacidosis, severe hypoglycemia, and diabetes complications. The effect of CGM was modeled as a persistent 1.1% reduction in HbA1c relative to SMBG based on US real-world evidence. Disutilities were based on published clinical trials and other relevant literature. The primary outcome was cost per quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed to test the validity of the model results when accounting for a plausible variation of inputs. In the base case analysis, CGM was dominant to SMBG, providing more QALYs (6.18 vs 5.97) at a lower cost ($70,137 vs $71,809) over the 10-year time horizon. A $10,456 increase in glucose monitoring costs was offset by a $12,127 reduction in treatment costs. Cost savings reflected avoidance of acute diabetic events (savings owing to reductions in severe hypoglycemia and diabetic ketoacidosis were $271 and $2,159, respectively) and a reduced cumulative incidence of diabetes complications, particularly renal failure (saving $5,292), myocardial infarction (saving $1,996), and congestive heart failure (saving $1,061). Scenario analyses were consistent with the base case results, and the incremental cost-effectiveness ratio for CGM vs SMBG ranged from dominant to cost-effective. In probabilistic analysis, CGM was 100% likely to be cost-effective at a willingness-to-pay threshold of $50,000/QALY. CGM is cost-effective compared with SMBG for US patients with type 2 diabetes mellitus receiving basal insulin therapy. This suggests that state Medicaid programs could benefit from broader coverage of CGM.

Clinical features, biomarkers and diabetic ketoacidosis at diagnosis of type 1 diabetes among children and adolescents in Sana’a, Yemen

IntroductionThere is little published information on type 1 diabetes (T1D) in children in Yemen. We aimed to identify the clinical characteristics, biomarkers and diabetic ketoacidosis (DKA) at diagnosis of T1D...

Diabetic ketoacidosis in youth with diabetes mellitus during the COVID-19 pandemic.

We sought to determine if the early months of the coronavirus disease 2019 (COVID-19) pandemic influenced pediatric diabetic ketoacidosis (DKA) hospitalization characteristics. This is a cross-sectional study of youth with laboratory-confirmed DKA admitted to a large tertiary children's hospital in the USA. Data were collected from admissions in March through July 2019 and March through July 2020, respectively. We evaluated the clinical characteristics of hospitalization, including demographic data and DKA severity. We used univariable ordinal logistic regression followed by multiple ordinal logistic regression to adjust for potential confounders. We included 137 children with diabetes admitted for DKA in the relevant period in 2019 and 173 patients admitted for DKA in the same period in 2020. Hemoglobin A1C (HbA1c) upon admission was higher in 2020 (median=12.2 %) than in 2019 (11.5 %, p=0.018). Children who were admitted with DKA in 2020 were less likely to be autoantibody positive than those in 2019 (83 vs. 91 %, p=0.028). In the univariable model, being admitted in 2020 was significantly associated with more severe DKA (p=0.038), as was HbA1c (p=0.001). After adjusting for HbA1c upon admission, admission year was no longer significantly associated with more severe DKA. In this study of pediatric diabetes of any type and duration of diabetes, youth admitted for DKA at the start of the COVID-19 pandemic, compared with those admitted during the year before, were more likely to have autoantibody-negative diabetes and had significantly higher HbA1c. Additionally, higher HbA1c seemed to mediate more severe DKA during the pandemic.