Risk Of Diabetic Ketoacidosis Research Articles

Effects of SGLT2 inhibitors on the cardiovascular outcomes in patients with cancer: a systematic review and meta-analysis

Abstract Introduction The incidence of cardiovascular diseases in cancer survivors has gradually increased due to well-documented drug-associated cardiotoxicity and the expanding population resulting from advances in cancer treatment. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) have demonstrated efficacy in reducing cardiovascular risk in patients with type 2 diabetes mellitus, independent of glycemic control. Previous bench and animal research, along with several cohort studies, suggest potential benefits of SGLT2 inhibitors on cardiovascular outcomes in patients with cancer, with or without anthracycline therapy. This systematic review and meta-analysis aim to explore the potential of SGLT2 inhibitors as a therapeutic intervention to reduce cardiovascular risks in cancer patients, especially those undergoing chemotherapy. Methods We systematically searched Cochrane, PubMed, and Embase from inception until February 29, 2024, without language restrictions. Observational cohort studies with a follow-up period of at least 1 year were included to analyze the effects of SGLT2 inhibitors on cardiovascular outcomes in type 2 diabetes patients with cancer. Inclusion and exclusion criteria were predefined. Using random-effects models, we calculated odds ratios (OR) and 95% confidence intervals (CI). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and explore the impact of SGLT2 inhibitors on mitigating cardiotoxicity. Primary outcomes of interest were mortality, heart failure hospitalization, sepsis, and diabetic ketoacidosis. Results Six studies involving 2959 patients in the SGLT2i group and 29169 patients in the non-SGLT2i group were included. Type 2 diabetes patients receiving SGLT2i exhibited significantly lower odds of mortality than those without SGLT2i (OR=0.34, 95% CI=[0.26-0.46], I²=77%). Subgroup analysis revealed a similar reduction in mortality among patients on SGLT2i treated with anthracyclines (OR=0.44, 95% CI=[0.23-0.82], I²=69%). Odds ratios for heart failure hospitalization and sepsis were also significantly lower in the SGLT2i group than the non-SGLT2i group (OR=0.46, 95% CI=[0.35-0.60], I²=0%, and OR=0.28, 95% CI=[0.20-0.40], I²=0%, respectively). The risk for diabetic ketoacidosis was not increased in the SGLT2i group (OR=0.66, 95% CI=[0.20-2.17], I²=0%). Conclusion SGLT2 inhibitors demonstrate a reduction in mortality, heart failure hospitalization, and sepsis in type 2 diabetes cancer patients treated with or without anthracyclines in cohort studies. Our findings support the need for further investigation through randomized controlled trials.Forest plots of mortality with subgroupForest plots of other primary outcomes

Efficacy and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors for the Primary Prevention of Cardiovascular, Renal Events and Safety Outcomes in Patients with Systemic Lupus Erythematosus and Comorbid Type 2 Diabetes: A Population-based Target Trial Emulation.

Patients with systemic lupus erythematosus (SLE) were excluded from sodium-glucose co-transporter 2 inhibitors (SGLT2i) clinical trials. It is unknown whether the cardiorenal benefits of SGLT2i extend to patients with SLE and comorbid type 2 diabetes (T2D). We performed an emulated clinical trial in an insurance-based cohort in the U.S., evaluating SGLT2i versus dipeptidyl peptidase 4 inhibitors (DPP4i) for primary prevention of cardiovascular, renal, and other clinical outcomes among patients with both SLE patients and comorbid T2D. SGLT2i initiators were matched to DPP4i initiators using propensity scores (PS) based on clinical and demographic factors. Hazard ratios (HR with 95% confidence intervals) were calculated using Cox models. Outcomes among 2,165 patients starting SGLT2i and 2,165 PS-matched patients starting DPP4i were compared. Over 753.1 (±479.2) mean days, SGLT2i recipients had significantly lower risks of incident acute kidney injury (HR 0.49, 95% CI 0.39-0.63), chronic kidney disease (HR 0.61, 0.50-0.76), end-stage renal disease (HR 0.40, 0.20-0.80), heart failure (HR 0.72, 0.56-0.92), and emergency department visits (HR 0.90, 0.82-0.99). Risks of all-cause mortality (HR 0.89, 0.65-1.21), lupus nephritis (HR 0.67, 0.38-1.15), myocardial infarction (HR 0.81, 0.54-1.23), stroke (HR 1.03, 0.74-1.44), and hospitalizations (HR 0.76, 0.51-1.12) did not differ. Genital infection risk (HR 1.31, 1.07-1.61) was increased, but urinary tract infection risk (HR 0.90, 0.79-1.03) did not differ. No significant difference was observed for diabetic ketoacidosis risk (HR 1.065, 0.53-2.14) and fractures (HR 0.95, 0.66-1.36). In this emulated clinical trial, SGLT2i vs. DPP4i use was associated with significantly reduced risks of several cardiorenal complications among patients with both SLE and T2D.

Sodium-Glucose Co-transporter-2 Inhibitors in Type 1 Diabetes Mellitus: The Framework for Recommendations for Their Potential Use.

The growing prevalence of overweight/obesity, the persistence of inadequate glycemic control among themajority of affected individuals, and thestill unacceptably high risk of cardiovascular morbidity and mortality among population with type 1 diabetes mellitus (T1D), impose an urgent need for theintroduction of non-insulin glucose-lowering agents in the therapeutic armamentarium. Given thattheir antihyperglycemic mechanism of action is independent of endogenous insulin secretion and thatthe observed cardio-renal benefits are unrelated to their glucose-lowering properties, one can speculate that the use of sodium-glucose co-transporter-2 inhibitors (SGLT2is) could provide benefits in T1D, similar to the ones observed among individuals with type 2 diabetes mellitus, chronic kidney disease (CKD), and heart failure. Available evidence from randomized controlled trials suggests that treatment with SGLT2is as adjunct to insulin in T1D results in modest reductions in glycated hemoglobin and body weight. Additionally, SGLT2is ameliorate albuminuria, and thus delay or prevent thedevelopment of CKD inT1D. However, use of SGLT2is is associated with an increased risk of diabetic ketoacidosis (DKA) in T1D. This commentary aims at providing a framework for practical recommendations regarding the potential use of SGLT2is in adults with T1D, based on the individual's risk level for DKA development, the presence of inadequate glycemic control and related cardio-renal complications.

Mitochondrial proteins as therapeutic targets in diabetic ketoacidosis: evidence from Mendelian randomization analysis.

Diabetic ketoacidosis (DKA) is a severe and potentially fatal acute complication in diabetic patients, commonly occurring in type 1 diabetes (T1D) but also seen in type 2 diabetes (T2D). The pathogenesis of DKA involves complex physiological processes that are not fully understood, especially the role of mitochondria. Mitochondria, known as the powerhouse of cells, plays a crucial role in oxidative phosphorylation and ATP production, which is vital in various metabolic diseases, including diabetes. However, the exact causal relationship between mitochondrial dysfunction and DKA remains unclear. This study employed Mendelian randomization (MR) analysis and protein-protein interaction (PPI) networks to systematically explore the causal relationships between mitochondrial DNA copy number (mtDNA-CN) and specific mitochondrial proteins with DKA. We used bidirectional MR analysis and genome-wide association study (GWAS) data from openGWAS database to investigate the causal effects of mtDNA-CN and 64 mitochondrial-related proteins on DKA and its subtypes (T1DKA, T2DKA, unspecified-DKA). The study revealed that increased mtDNA-CN significantly reduces the risk of DKA, whereas the effect of DKA on mtDNA-CN was not significant. Mitochondrial-related proteins such as MRPL32, MRPL33, COX5B, DNAJC19, and NDUFB8 showed a negative causal relationship with DKA, indicating their potential protective roles. Conversely, ATP5F1B and COX4I2 have a positive causal relationship with DKA, indicating that excessive ATP production in diabetic patients may be detrimental to health and increase the risk of severe complications such as DKA. The results emphasize the necessity of protecting mitochondrial function in order to reduce the risk of DKA. The study offers novel perspectives on the molecular pathways involved in DKA, emphasizing the critical functions of mt-DNA and distinct proteins. These evidences not only enhance our comprehension of the implications of mitochondrial dysfunction in diabetes-related complications but also identify potential therapeutic targets for individualized treatment approaches, thereby making a substantial contribution to clinical care and public health initiatives.

Insulin Pump Use and Diabetic Ketoacidosis Risk in Type 1 Diabetes: Secular Trends over Four Decades.

Introduction: Continuous subcutaneous insulin infusion (CSII) in type 1 diabetes has been regarded as a major diabetic ketoacidosis (DKA) risk factor. We aimed to determine secular trends in risk since CSII implementation in the 1980s. Research Design and Methods: We assessed the relationship between time-varying CSII use and DKA events from 1983 to 2017 and by each decade in the 1441 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study participants using crude and adjusted Cox proportional hazards models. Results: Time-varying CSII exposure was associated with significantly higher DKA risk in the 1980s (adjusted hazard ratio [HR] 5.81; 95% confidence interval [CI] 3.28-10.29; P < 0.001), but in the 2010s, this risk was not significantly elevated (adjusted HR 1.24; 95% CI 0.73-2.12; P = 0.43). Conclusions: DKA risk associated with CSII in type 1 diabetes has declined substantially since the 1980s such that the remaining risk in the past decade appears to be of low magnitude.

Acetazolamide Therapy and Kidney Function in Persons with Non-albuminuric Diabetes Mellitus Type 1

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower the risk of kidney failure in persons with type 2 diabetes. The presumed mechanism of action is through greater delivery of sodium to the distal tubule, activation of tubuloglomerular feedback which lowers glomerular filtration rate (GFR) and intra-glomerular pressure. SGLT2is are not approved for use in persons with type 1 diabetes due to the risk of diabetic ketoacidosis. Acetazolamide, a proximal tubule diuretic, delivers more sodium to the distal nephron, and may activate tubuloglomerular feedback in a similar way to SGLT2is without a higher risk of diabetic ketoacidosis. The kidney effects and safety of acetazolamide in persons with type 1 diabetes have not been well studied. Methods: We conducted a dose-escalation trial to determine the effects of 3 dosages of oral acetazolamide (62.5mg, 125mg, and 250mg, all twice-daily) in 12 persons with type 1 diabetes. Participants were treated for 2 weeks followed by a 2-week washout before exposure to the next dosage level. Blood and urine chemistries, as well as iohexol measured GFR, were assessed before and after each treatment interval. We aimed to identify a dose that maximized measured GFR reductions while minimizing adverse effects. Results: The mean age was 46±17 years, 100% were White, and 75% were female. The mean measured GFR was 89±18ml/min/1.73m2 at baseline. Acetazolamide reduced measured GFR by 15% (95% CI 9, 21), 14% (95% CI 7, 21), and 15% (95% CI 10, 21) after 2 weeks at the 62.5mg, 125mg, and 250mg twice-daily dosage levels respectively. The measured GFR reduction was fully reversed after each 2-week washout. Serum bicarbonate was reduced by 2.3, 4.2 and 4.4 mEq/L with escalating doses, and no episodes of hypokalemia (&lt; 3.5 mEq/L) were observed. Conclusions: Among persons with type 1 diabetes and preserved kidney function, acetazolamide caused an acute, reversible reduction in measured GFR without effects on glucose metabolism.

6541 Recurrent Euglycemic Diabetic Ketoacidosis And Myonecrosis In A Patient Previously Thought To Have Type 2 Diabetes Mellitus

Abstract Disclosure: K. Haridas: None. M.M. McConnell : None. Introduction: Euglycemic diabetic ketoacidosis (DKA) is a well-recognized complication with the use of sodium linked cotransport of glucose-2 (SGLT2) inhibitors. Diabetic myonecrosis is a rare complication of diabetes mellitus caused by spontaneous death of muscle due to microvascular ischemia. Clinical Case: A 48-year-old male diagnosed with Type 2 Diabetes Mellitus with HbA1c 11.3%, treated with Empagliflozin and basal-bolus insulin was admitted to the hospital with left thigh pain and anorexia. Physical examination was notable for BMI of 19kg/m2 and left lateral thigh induration. Laboratory evaluation revealed venous pH 7.1, bicarbonate 10mmol/L (20-30), anion gap 32mmol/L(8-12), glucose 168mg/dl (65-99), ESR 67mm/h (&amp;lt;=12), Creatinine Kinase 31 U/L (63-473), glucosuria (4+) and ketonuria (4+). He was diagnosed with euglycemic DKA due to SGLT2 inhibitor. He was also diagnosed with Type 1 Diabetes Mellitus (T1DM) based on undetectable C-peptide and GAD antibody titer 64.3IU/ml(&amp;lt;5). MRI of the left thigh revealed an area of diabetic myonecrosis, measuring 11cm. He was treated with continuous insulin infusion. On hospital day 3, after resolution of the anion gap metabolic acidosis, transition was made to basal-bolus insulin. On hospital day 5, recurrent euglycemic DKA was diagnosed with bicarbonate 15mmol/L, anion gap 18mmol/L, beta-hydroxybutyrate 49.6mg/dl (&amp;lt;=3mg/dl), glucose 185mg/dl, glucosuria (4+) and ketonuria (4+). Continuous insulin infusion was restarted. On hospital day 8, transition was made to subcutaneous insulin. Diabetic myonecrosis was initially managed conservatively with analgesics, aspirin, and physical therapy. Due to worsening leukocytosis on hospital day 13, Ceftriaxone was started and surgical debridement was performed, revealing a loculated abscess within necrotic muscle. Empagliflozin was discontinued at discharge. Discussion: The risk of euglycemic DKA with SGLT2i use is increased in patients with T1DM and decreased oral intake, and insults like trauma or surgery as seen in this patient. Although the half-life of empagliflozin is 12 to 14 hours, there have been case reports of persistent or recurrent euglycemic DKA for 7-12 days from the time of last dose. The continued glucosuria and ketonuria in this patient with serum glucose levels below the renal threshold confirmed the recurrence. Diabetic myonecrosis usually affects the muscles of the proximal lower extremities and is seen in patients with poorly controlled diabetes with microvascular complications, between one and two decades after diagnosis, as in this patient. Conclusion: A high index of suspicion for recurrent euglycemic DKA must be maintained in patients who have new or persistent high anion gap metabolic acidosis until 2 weeks from last dose of SGLT2 inhibitor. Diabetic myonecrosis, especially if complicated by abscess formation, may require surgical intervention. Presentation: 6/1/2024

7555 Gender-Related Differences in Outcomes of Patients With Diabetic Ketoacidosis: An Analysis of the National Readmission Database

Abstract Disclosure: E. Ahsan: None. C. Lesniak: None. M. Akula: None. K. Hu: None. K. Chalasani: None. R. Ong: None. S. Holland: None. M. Hossain: None. J. Cheng: None. J. Heaton: None. Introduction: Diabetic ketoacidosis (DKA), one of the most serious complications of diabetes, is a significant cause of morbidity and mortality. Hospitalizations for DKA have increased significantly over the past two decades. Despite this, there is a notable absence of data on gender-related variations in the clinical characteristics and outcomes of individuals hospitalized with DKA. Understanding these distinctions is crucial for optimizing disease prevention and care. Thus, the primary aim of this study was to explore whether gender influences the outcomes of DKA. Methodology: We analyzed the National Readmissions Database (NRD) from 2016 to 2020 by evaluating patients admitted with a primary diagnosis of DKA without coma. Patients were included if they were at least 18 years old and admitted between January and November. Patients meeting inclusion criteria were stratified by sex. The groups were assessed for 30-day readmissions, all causes of mortality, length of stay, and total cost. Descriptive statistics, Cox proportional hazards, and adjusted Wald tests were used to compare the groups. Results: Between 2016 and 2020, 642,431 patients met the inclusion criteria with a median age of 44, of which 46.5% were female and 53.5% were male. Early readmission occurred in 33,639.20 females and 31,101.92 males. Cox regression analysis showed a significant difference in readmission risk for female patients than males (HR 1.20, 95% CI 1.17-1.22, P = &amp;lt;0.001). The length of stay was higher in male patients than in female patients (adjusted Wald test, P =&amp;lt;0.001). Inpatient mortality was higher in females than in males (Cox regression analysis, P = 0.009). Total cost was higher in males compared to females (adjusted Wald test, P = &amp;lt;0.001). Conclusion: Regrettably, the majority of studies on diabetic ketoacidosis (DKA) have not given due attention to gender differences. Our study, however, reveals statistically significant variations in in-hospital mortality and 30-day readmission rates between men and women hospitalized with DKA, with women exhibiting higher rates than men. Additionally, the length of stay and total cost were found to be higher for men. To comprehend the underlying reasons for these distinctions, further investigations are warranted. Early introduction and intensification of insulin therapy may prove beneficial for this patient group in mitigating the risk of DKA and other complications associated with diabetes mellitus. Presentation: 6/2/2024

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.

Integrating randomized controlled trials and non-randomized studies of interventions to assess the effect of rare events: a Bayesian re-analysis of two meta-analyses

BackgroundThere is a growing trend to include non-randomised studies of interventions (NRSIs) in rare events meta-analyses of randomised controlled trials (RCTs) to complement the evidence from the latter. An important consideration when combining RCTs and NRSIs is how to address potential bias and down-weighting of NRSIs in the pooled estimates. The aim of this study is to explore the use of a power prior approach in a Bayesian framework for integrating RCTs and NRSIs to assess the effect of rare events.MethodsWe proposed a method of specifying the down-weighting factor based on judgments of the relative magnitude (no information, and low, moderate, serious and critical risk of bias) of the overall risk of bias for each NRSI using the ROBINS-I tool. The methods were illustrated using two meta-analyses, with particular interest in the risk of diabetic ketoacidosis (DKA) in patients using sodium/glucose cotransporter-2 (SGLT-2) inhibitors compared with active comparators, and the association between low-dose methotrexate exposure and melanoma.ResultsNo significant results were observed for these two analyses when the data from RCTs only were pooled (risk of DKA: OR = 0.82, 95% confidence interval (CI): 0.25–2.69; risk of melanoma: OR = 1.94, 95%CI: 0.72–5.27). When RCTs and NRSIs were directly combined without distinction in the same meta-analysis, both meta-analyses showed significant results (risk of DKA: OR = 1.50, 95%CI: 1.11–2.03; risk of melanoma: OR = 1.16, 95%CI: 1.08–1.24). Using Bayesian analysis to account for NRSI bias, there was a 90% probability of an increased risk of DKA in users receiving SGLT-2 inhibitors and an 91% probability of an increased risk of melanoma in patients using low-dose methotrexate.ConclusionsOur study showed that including NRSIs in a meta-analysis of RCTs for rare events could increase the certainty and comprehensiveness of the evidence. The estimates obtained from NRSIs are generally considered to be biased, and the possible influence of NRSIs on the certainty of the combined evidence needs to be carefully investigated.

Examining capillary ketone testing in hospitalised patients: indications and outcomes.

Elevated blood ketone levels (ketosis) in inpatients with diabetes can herald diabetic ketoacidosis (DKA). However, ketosis can also occur in individuals without diabetes in certain settings. It is unclear what proportion of inpatients with ketosis are in DKA and which patients are at the highest risk of DKA. This study determined that many ketone tests are performed in individuals at low risk of DKA, and a β-hydroxybutyrate <1.0 mmol/L had a low incidence of DKA and less need for escalation in their management.

A Machine Learning Model for Risk Stratification of Postdiagnosis Diabetic Ketoacidosis Hospitalization in Pediatric Type 1 Diabetes: Retrospective Study.

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in pediatric type 1 diabetes (T1D), occurring in approximately 20% of patients, with an economic cost of $5.1 billion/year in the United States. Despite multiple risk factors for postdiagnosis DKA, there is still a need for explainable, clinic-ready models that accurately predict DKA hospitalization in established patients with pediatric T1D. We aimed to develop an interpretable machine learning model to predict the risk of postdiagnosis DKA hospitalization in children with T1D using routinely collected time-series of electronic health record (EHR) data. We conducted a retrospective case-control study using EHR data from 1787 patients from among 3794 patients with T1D treated at a large tertiary care US pediatric health system from January 2010 to June 2018. We trained a state-of-the-art; explainable, gradient-boosted ensemble (XGBoost) of decision trees with 44 regularly collected EHR features to predict postdiagnosis DKA. We measured the model's predictive performance using the area under the receiver operating characteristic curve-weighted F1-score, weighted precision, and recall, in a 5-fold cross-validation setting. We analyzed Shapley values to interpret the learned model and gain insight into its predictions. Our model distinguished the cohort that develops DKA postdiagnosis from the one that does not (P<.001). It predicted postdiagnosis DKA risk with an area under the receiver operating characteristic curve of 0.80 (SD 0.04), a weighted F1-score of 0.78 (SD 0.04), and a weighted precision and recall of 0.83 (SD 0.03) and 0.76 (SD 0.05) respectively, using a relatively short history of data from routine clinic follow-ups post diagnosis. On analyzing Shapley values of the model output, we identified key risk factors predicting postdiagnosis DKA both at the cohort and individual levels. We observed sharp changes in postdiagnosis DKA risk with respect to 2 key features (diabetes age and glycated hemoglobin at 12 months), yielding time intervals and glycated hemoglobin cutoffs for potential intervention. By clustering model-generated Shapley values, we automatically stratified the cohort into 3 groups with 5%, 20%, and 48% risk of postdiagnosis DKA. We have built an explainable, predictive, machine learning model with potential for integration into clinical workflow. The model risk-stratifies patients with pediatric T1D and identifies patients with the highest postdiagnosis DKA risk using limited follow-up data starting from the time of diagnosis. The model identifies key time points and risk factors to direct clinical interventions at both the individual and cohort levels. Further research with data from multiple hospital systems can help us assess how well our model generalizes to other populations. The clinical importance of our work is that the model can predict patients most at risk for postdiagnosis DKA and identify preventive interventions based on mitigation of individualized risk factors.

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...

Management of diabetic ketoacidosis in children: Does early insulin glargine help improve outcomes?

Rebound hyperglycemia following the resolution of diabetic ketoacidosis (DKA) is common in pediatric patients with type 1 diabetes, increasing the risk of recurrent DKA and complicating the transition to subcutaneous insulin. Multiple studies suggest that early administration of long-acting insulin analogs during DKA management safely improves this transition. This study aimed to determine whether early insulin glargine administration in children with DKA prevents rebound hyperglycemia and recurrent ketosis without increasing the rate of hypoglycemia or hypokalemia. Patients aged <21 years presenting with DKA to Children's Mercy Kansas City between October 2012 and October 2016 were reviewed. They were categorized as Early (>4 h of overlap with intravenous [IV] insulin) and Late (<2 h of overlap) cohorts. We reviewed 546 DKA admissions (365 Early and 181 Late). Rebound hyperglycemia (>180 mg/dL) was lower in the Early group (66% vs. 85%, p ≤ 0.0001). Hypoglycemia (<70 mg/dL) during IV insulin administration was higher in the Early group than in the Late group (27% vs. 19%, p = 0.042). Hypoglycemia within 12 h of IV insulin discontinuation was lower in the Early group (16% vs. 26%, p = 0.012). Recurrent ketosis, hypokalemia, and cerebral edema were not different between the groups. Early glargine administration in pediatric DKA management is safe, decreases the rate of rebound hyperglycemia, and improves the transition to subcutaneous insulin. Hypoglycemia is less frequent following IV insulin discontinuation with early glargine, but the IV insulin rate may need to be reduced to minimize hypoglycemia during IV insulin infusion.

Association of sodium glucose co-transporter-2 inhibitors with risk of diabetic ketoacidosis among hospitalized patients: A multicentre cohort study

IntroductionSodium glucose co-transporter-2 inhibitors (SGLT-2i) are increasingly being used among hospitalized patients. Our objective was to assess the risk of diabetic ketoacidosis (DKA) among hospitalized patients receiving an SGLT-2i. Research design and methodsWe conducted a multicentre cohort study of patients hospitalized at 19 hospitals. We included patients over 18 years of age who received an SGLT-2i or a dipeptidyl peptidase-4 inhibitor (DPP-4i) in hospital. The primary outcome was the risk of DKA during their hospitalization. Results61,517 patients received a DPP-4i and 11,061 received an SGLT-2i. The risk of inpatient DKA was 0.07 % (N = 41 events) among adults who received a DPP-4i and 0.18 % (N = 20 events) among adults who received an SGLT-2i; adjusted odds ratio of 3.30 (95 % CI: 1.85–5.72). ConclusionsIn hospitalized patients, the absolute risk of DKA was 0.2 %, which corresponded to a three-fold higher relative risk.

A Review of Sotagliflozin: The First Dual SGLT-1/2 Inhibitor.

Sotagliflozin (trade name INFEPA) is a novel dual sodium-glucose cotransporter-1 and -2 (SGLT-1/2) inhibitor that was developed by Lexicon Pharmaceuticals. It has emerged as a promising therapy for managing heart failure and other cardiovascular complications associated with type 2 diabetes mellitus (T2DM). Its dual inhibition of SGLT-1 and SGLT-2 receptors uniquely decreases glucose absorption in the intestine in addition to decreasing renal glucose reabsorption, leading to improved glycemic control and cardio-reno protection. Clinical trials have demonstrated its efficacy in reducing cardiovascular death, heart failure hospitalizations, and urgent visits, particularly in T2DM patients with chronic kidney disease (CKD). The drug was approved in 2023 by the Food and Drug Administration for reducing cardiovascular death and heart failure in T2DM patients with CKD and those with heart failure, irrespective of diabetic status or ejection fraction. However, despite its considerable therapeutic potential, sotagliflozin does pose notable adverse effects, including diabetic ketoacidosis, genital infections, and diarrhea. As a result, it has faced regulatory challenges in certain regions, notably the United States. The Food and Drug Administration has so far withheld approval for sotagliflozin in the treatment of type 1 diabetes due to concerns about its safety profile, specifically the risk of diabetic ketoacidosis, although Lexicon Pharmaceuticals plans to submit another new drug application for this use in 2024. Further investigation and clinical trials are warranted to fully elucidate sotagliflozin's impact on diabetes and CKD.

Predictive factors of diabetic ketoacidosis in patients with newly onset type 1 diabetes: A single center study

BackgroundDiabetic ketoacidosis is a severe metabolic emergency often associated with the onset of Type 1 Diabetes Mellitus, with significant morbidity and mortality. Its incidence as the initial presentation of Type 1 Diabetes Mellitus varies widely by country. In Morocco, there is a lack of comprehensive research on the prevalence and risk factors of diabetic ketoacidosis in children with newly diagnosed Type 1 Diabetes Mellitus, highlighting the need for this study. ObjectivesThe aim of our study was to analyze the predictive factors of diabetic ketoacidosis at the onset of Type 1 Diabetes Mellitus in children and adolescents at a single medical center in Morocco to develop prevention and management strategies. MethodsA retrospective, single-center study including 200 patients aged between 1 and 18 years at Type 1 Diabetes Mellitus onset, between September 2019 and September 2023. The population was divided into two groups according to the presence or absence of diabetic ketoacidosis. Medical records provided data for analysis with SPSS v21, employing Chi-square and Student's t-tests, followed by logistic regression to identify predictors of diabetic ketoacidosis. ResultsMultivariate regression identified several factors that were significantly associated with diabetic ketoacidosis at presentation, including age below 5 years (OR: 3.98; p = 0.021 compared to 6–10 years and OR: 5.07; P = 0.003 compared to 11–18 years), rural living (OR: 2.95; p = 0.032), low family income (OR: 9.22; p < 0.001), delayed diagnosis (OR: 21.27; p < 0.001), longer symptom duration before diagnosis (OR: 1.02; p = 0.010), preceding infections (OR: 2.72; p = 0.019), and lower vitamin D levels (OR: 0.90; p = 0.011). ConclusionOur findings underscore the critical need for increased awareness, education, use of point-of-care glucose testing, and targeted interventions in rural areas, in order to reduce the incidence of diabetic ketoacidosis. We also highlight the potential role of vitamin D in increasing the risk of diabetic ketoacidosis at the onset of Type 1 Diabetes Mellitus. This study provides important information on the present state of pediatric diabetes care in our country, and suggests target points for future interventions and research.

914-P: Association of Sodium–Glucose Cotransporter 2 Inhibitors with Risk of Diabetic Ketoacidosis among Hospitalized Patients—A Multicentre Cohort Study

914-P: Association of Sodium–Glucose Cotransporter 2 Inhibitors with Risk of Diabetic Ketoacidosis among Hospitalized Patients—A Multicentre Cohort Study

406-P: Kidney Disease and Risk of Diabetic Ketoacidosis in Type 1 Diabetes

406-P: Kidney Disease and Risk of Diabetic Ketoacidosis in Type 1 Diabetes

Safety and effectiveness of SGLT2 inhibitors in a UK population with type 2 diabetes and aged over 70 years: an instrumental variable approach.

Older adults are under-represented in trials, meaning the benefits and risks of glucose-lowering agents in this age group are unclear. The aim of this study was to assess the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in people with type 2 diabetes aged over 70 years using causal analysis. Hospital-linked UK primary care data (Clinical Practice Research Datalink, 2013-2020) were used to compare adverse events and effectiveness in individuals initiating SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i). Analysis was age-stratified: <70 years (SGLT2i n=66,810, DPP4i n=76,172), ≥70 years (SGLT2i n=10,419, DPP4i n=33,434). Outcomes were assessed using the instrumental variable causal inference method and prescriber preference as the instrument. Risk of diabetic ketoacidosis was increased with SGLT2i in those aged ≥70 (incidence rate ratio compared with DPP4i: 3.82 [95% CI 1.12, 13.03]), but not in those aged <70 (1.12 [0.41, 3.04]). However, incidence rates with SGLT2i in those ≥70 was low (29.6 [29.5, 29.7]) per 10,000 person-years. SGLT2i were associated with similarly increased risk of genital infection in both age groups (incidence rate ratio in those <70: 2.27 [2.03, 2.53]; ≥70: 2.16 [1.77, 2.63]). There was no evidence of an increased risk of volume depletion, poor micturition control, urinary frequency, falls or amputation with SGLT2i in either age group. In those ≥70, HbA1c reduction was similar between SGLT2i and DPP4i (-0.3 mmol/mol [-1.6, 1.1], -0.02% [0.1, 0.1]), but in those <70, SGLT2i were more effective (-4 mmol/mol [4.8, -3.1], -0.4% [-0.4, -0.3]). Causal analysis suggests SGLT2i are effective in adults aged ≥70 years, but increase risk for genital infections and diabetic ketoacidosis. Our study extends RCT evidence to older adults with type 2 diabetes.