Feature selection and risk prediction for diabetic patients with ketoacidosis based on MIMIC-IV.

Background: Diabetic ketoacidosis (DKA) is a frequent acute complication of diabetes mellitus (DM). It develops quickly, produces severe symptoms, and greatly affects the lives and health of individuals with DM.This article utilizes machine learning methods to examine the baseline characteristics that significantly contribute to the development of DKA. Its goal is to identify and prevent DKA in a targeted and early manner. Methods: This study selected 2382 eligible diabetic patients from the MIMIC-IV dataset, including 1193 DM patients with ketoacidosis and 1186 DM patients without ketoacidosis. A total of 42 baseline characteristics were included in this research. The research process was as follows: Firstly, important features were selected through Pearson correlation analysis and random forest to identify the relevant physiological indicators associated with DKA. Next, logistic regression was used to individually predict DKA based on the 42 baseline characteristics, analyzing the impact of different physiological indicators on the experimental results. Finally, the prediction of ketoacidosis was performed by combining feature selection with machine learning models include logistic regression, XGBoost, decision tree, random forest, support vector machine, and k-nearest neighbors classifier. Results: Based on the importance analysis conducted using different feature selection methods, the top five features in terms of importance were identified as mean hematocrit (haematocrit_mean), mean hemoglobin (haemoglobin_mean), mean anion gap (aniongap_mean), age, and Charlson comorbidity index (charlson_comorbidity_index). These features were found to have significant relevance in predicting DKA. In the individual prediction using logistic regression, these five features have been proven to be effective, with F1 scores of 1.000 for hematocrit mean, 0.978 for haemoglobin_mean, 0.747 for age, 0.692 for aniongap_mean and 0.666 for charlson_comorbidity_index. These F1 scores indicate the effectiveness of each feature in predicting DKA, with the highest score achieved by mean hematocrit. In the prediction of DKA using machine learning models, including logistic regression, XGBoost, decision tree, and random forest demonstrated excellent results, achieving an F1 score of 1.000. Additionally, by applying feature selection techniques, noticeable improvements were observed in the experimental performance of the support vector machine and k-nearest neighbors classifier. Conclusion: The study found that hematocrit, hemoglobin, anion gap, age, and Charlson comorbidity index are closely associated with ketoacidosis. In clinical practice, these five baseline characteristics should be given with the special attention to achieve early detection and treatment, thus reducing the incidence of the disease.

Care, control and complications of hospitalised patients with type 1 diabetes in China: A nationwide-based registry study.

AIMS: To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S). MATERIALS AND METHODS: Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months. RESULTS: Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A1c (HbA1c) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years. CONCLUSIONS: In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally.

Incidence and determinants of diabetic ketoacidosis among people with diabetes in Woldiya comprehensive specialized hospital, Ethiopia: a retrospective cohort study.

INTRODUCTION: Diabetic ketoacidosis is an acute complication of diabetes mellitus that is characterised by hyperglycemia, acidosis, and ketonuria. Diabetes is the most challenging public health problem in the twenty-first century for both developed and developing countries. OBJECTIVE: To assess the incidence of Diabetic ketoacidosis and its determinants among adult people with diabetes at an Ethiopian Hospital. METHOD: An institution-based retrospective cohort study was conducted among 390 adult people with diabetes attending services at Wolida Comprehensive Specialized Hospital. The consecutive sampling method was used to select study participant charts. Data were collected using a checklist prepared from different literature. The data were entered into EPI data version 4.6.0.5 and exported to STATA version 14.0 for further analysis. The Wiebull model was the best fitted model that was selected using the log-likelihood ratio method and the Akakian information criterion. Hazard ratios with their 95% confidence interval and p-value were computed. RESULT: From the total 405 charts reviewed, 390 adult charts were included for analysis. A total of 121 DKA occurred from 5471 person-months of observation. The overall incidence rate of diabetic ketoacidosis was found to be 2.2 per 100 person-months (95% CI: 1.8- 2.6). Being urban dweller (AHR: 0.59, 95% CI: 0.36-0.99), having no family history of DM (AHR: 0.55, 95%CI: 0.31-0.97), presence of infection (AHR: 2.60, 95%CI = 1.06-6.39), having of any comorbidities (AHR: 4.31, 95% CI: 1.70-10.90), and having poor glycemic control (AHR: 7.45, 95% CI: 3.84-14.47) were significant determinants. CONCLUSION AND RECOMMENDATIONS: The overall incidence of diabetic ketoacidosis in study area was relatively high. Poor glycemic control, the presence of infection, and comorbidity were determinants of diabetic ketoacidosis. There is a need to have close follow-up of people with diabetes who have comorbidity, infection, and poor glycemic control.

Prevalence and prognosis of fulminant type 1 diabetes mellitus in The Middle East: a comparative analysis in a 5-year nationwide cohort.

PURPOSE: To analyze the prevalence and progression of fulminant type 1 diabetes (FT1D) in Qatar. METHODS: This retrospective study analyzed consecutive index- diabetic ketoacidosis (DKA) admissions (2015-2020) among patients with new-onset T1D (NT1D) in Qatar. RESULTS: Of the 242 patients, 2.5% fulfilled the FT1D diagnostic criteria. FT1D patients were younger (median-age 4-years vs.15-years in classic-T1D). Gender distribution in FT1D was equal, whereas the classic-T1D group showed a female predominance at 57.6% (n = 136). FT1D patients had a mean C-peptide of 0.11 ± 0.09 ng/ml, compared to 0.53 ± 0.45 ng/ml in classic-T1D. FT1D patients had a median length of stay (LOS) of 1 day (1-2.2) and a DKA duration of 11.25 h (11-15). The median (length of stay) LOS and DKA duration in classic-T1D patients were 2.5 days (1-3.9) and 15.4 h (11-23), respectively. The FT1D subset primarily consisted of moderate (83.3%) and severe 916.7%) DKA, whereas classic T1D had 25.4% mild, 60.6% moderate, and 14% severe DKA cases. FT1D was associated with a higher median white cell count (22.3 × 103/uL) at admission compared to classic T1D (10.6 × 103/uL). ICU admission was needed for 66.6% of FT1D patients, compared to 38.1% of classic-T1D patients. None of the patients in the FT1D group had mortality, while two died in the classic-T1D group. CONCLUSION: This is the first study establishing the existence of FT1D in ME, which presented distinctively from classic-T1D, exhibiting earlier age onset and higher critical care requirements. However, the clinical outcomes in patients with FT1D seem similar to classic T1D.

Burden of diabetic ketoacidosis among patients with diabetes mellitus in Ethiopia: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to assess the magnitude and determinants of diabetic ketoacidosis (DKA) among patients with diabetes mellitus (DM) in Ethiopia. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Age 15 and above all patients with diabetes with the diagnosis of DKA in Ethiopia DATA SOURCE: PubMed/MEDLINE, Cochrane Library, Science Direct, HINARI, Google Scholar and grey literatures were accessed to find relevant articles. Studies that have been conducted and reported in English language, articles with an available full-text, and observational studies were included. The task of searching sources was carried out from all stated electronic databases performed during 15 April-29 April 2023. PRIMARY AND SECONDARY OUTCOME MEASURES: Eligible studies were critically appraised by three independent reviewers for methodological quality in the review using standardised critical appraisal instruments from Joanna Briggs Institute (JBI) for observational studies. After the finally extracted studies were exported, systematic review and meta-analysis were conducted using Unified Management, Assessment and Review of Information (JBI SUMARI) (JBI, Adelaide, Australia) and STATA V.17 software. Sensitivity tests were done, and funnel plot inspections with Egger's test were used to check for publication bias. RESULT: From a total of 19 studies with 6498 study participants, the pooled prevalence of DKA among patients with DM in Ethiopia was 30.92% (95% CI 29.96 to 31.89) with a significant statistical heterogeneity (I2=99.2, p=<0.001). Sensitivity analysis suggested that three studies showed deviations from the estimated pooled prevalence. A funnel plot inspection and Egger's test indicated the absence of a publication bias. CONCLUSION: This systematic review and meta-analysis revealed that the prevalence of DKA among patients with DM in Ethiopia was 30.92%. Besides, different behavioural and clinical determinants of DKA among patients with DM were identified. However, further studies should be conducted, particularly on the possible determinants of DKA, and different stakeholders should be engaged to minimise its burden.

Clinical nomogram prediction model to assess the risk of prolonged ICU length of stay in patients with diabetic ketoacidosis: a retrospective analysis based on the MIMIC-IV database.

BACKGROUND: The duration of hospitalization, especially in the intensive care unit (ICU), for patients with diabetic ketoacidosis (DKA) is influenced by patient prognosis and treatment costs. Reducing ICU length of stay (LOS) in patients with DKA is crucial for optimising healthcare resources utilization. This study aimed to establish a nomogram prediction model to identify the risk factors influencing prolonged LOS in ICU-managed patients with DKA, which will serve as a basis for clinical treatment, healthcare safety, and quality management research. METHODS: In this single-centre retrospective cohort study, we performed a retrospective analysis using relevant data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Clinical data from 669 patients with DKA requiring ICU treatment were included. Variables were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) binary logistic regression model. Subsequently, the selected variables were subjected to a multifactorial logistic regression analysis to determine independent risk factors for prolonged ICU LOS in patients with DKA. A nomogram prediction model was constructed based on the identified predictors. The multivariate variables included in this nomogram prediction model were the Oxford acute severity of illness score (OASIS), Glasgow coma scale (GCS), acute kidney injury (AKI) stage, vasoactive agents, and myocardial infarction. RESULTS: The prediction model had a high predictive efficacy, with an area under the curve value of 0.870 (95% confidence interval [CI], 0.831-0.908) in the training cohort and 0.858 (95% CI, 0.799-0.916) in the validation cohort. A highly accurate predictive model was depicted in both cohorts using the Hosmer-Lemeshow (H-L) test and calibration plots. CONCLUSION: The nomogram prediction model proposed in this study has a high clinical application value for predicting prolonged ICU LOS in patients with DKA. This model can help clinicians identify patients with DKA at risk of prolonged ICU LOS, thereby enhancing prompt intervention and improving prognosis.

Outcomes associated with a variable rate insulin infusion diabetic ketoacidosis protocol.

AIMS: To relate adverse events with glucose correction rates in diabetic ketoacidosis (DKA) using variable rate intravenous insulin-infusions (VRIII). METHODS: Retrospective, observational study in adults with DKA who received insulin infusions between 2012 and 2017 at St Vincent's Hospital, Melbourne. Early correction of hyperglycaemia (<10 mmol/L) was evaluated for association with hypoglycaemia (<4.0 mmol/L), hypokalaemia (potassium <3.3 mmol/L) and clinical outcomes via regression analysis. RESULTS: The study involved 97 patients, with 93 % having type 1 diabetes. The mean age was 38 years, 47 % were women and 35 % were admitted to intensive care. Hypoglycaemia rates during 12 and 24 h of treatment were 6.2 % and 8.2 %, respectively with 58 % of patients recording their first BGL <10 mmol/L within 12 h and 88 % within 24 h. Ketone clearance time averaged at 15.6 h. Hyperglycaemia correction rates to <10 mmol/L were not different in those with/without hypoglycaemia at 12/24 h, in multivariate analysis including admission BGL. Hypokalaemia occurred in 40.2 % of patients and was associated with lower pH but not BGL correction rates. CONCLUSION: The VRIII protocol achieved early hyperglycaemia correction and ketoacidosis reversal with low hypoglycaemia risk. However, high hypokalaemia rates suggest the need for aggressive potassium replacement, especially in markedly acidotic patients.

Mortality Due to Hyperglycemic Crises in the US, 1999-2022.

This study analyzes trends in US mortality attributed to both diabetic ketoacidosis and hyperosmolar hyperglycemic state from 1999-2022.

Characterization of newly diagnosed type 1 diabetes in children and adolescents from 2017 to 2022 in China: a single-center analysis.

OBJECTIVE: This study investigated the characteristics of newly diagnosed type 1 diabetes mellitus (T1DM) related to autoimmunity and the frequency of diabetic ketoacidosis (DKA) in children and adolescents from 2017-2022 in China. RESEARCH DESIGN AND METHODS: Single-center regional data from the Department of Pediatric Endocrinology, Tongji Hospital, were used to compare 88 children and adolescents newly diagnosed with T1DM from 2020 to 2022 (i.e. during the COVID-19 pandemic in China) and 76 children and adolescents diagnosed with T1DM from 2017 to 2019. Auto-antibodies, including glutamic acid decarboxylase-65 and insulin auto-antibodies, were detected by enzyme-linked immunoassays. DKA was defined as a pH < 7.3 and/or a bicarbonate level < 15 mmol/L. RESULTS: The median age of the 164 children and adolescents newly diagnosed with T1DM from 2017 to 2022 was 7.0 years (interquartile range [IQR]: 3.8-10.0 years; 51.83% male). The mean annual incidence of T1DM was 2.98 per 1,000,000 child years. The estimated frequency of auto-antibody positivity was 51.22% (n = 84), and there was no difference between the 2020-2022 group and 2017-2019 group (55.68% [n = 49] vs. 46.5% [n = 35]; p = 0.219). The frequency of DKA among the entire cohort was 57.93% (n = 95), and peaked in 2020 at 78.9% (15/19 patients). The frequency of DKA was not significantly higher in the 2020-2022 group compared with the 2017-2019 group (60.23% [n = 53] vs. 55.26% [n = 42]; p = 0.521). We found no significant difference in the frequency of DKA between patients who were negative vs. positive for auto-antibodies in the 2020-2022 group (64.10% [n = 25] vs. 57.14% [n = 28], p > 0.05). The C-peptide level and HbA1c (%) were positively correlated with onset age (R1 = 0.389, p < 0.01; R2 = 0.371, p < 0.01), and the estimated mean C-peptide level was 0.26 ng/ml (IQR: 0.2-0.4 ng/ml) in patients with DKA and 0.370 ng/ml (IQR: 0.2-0.6 ng/ml) in patients without DKA (p = 0.044). CONCLUSIONS: This study showed the annual incidence of T1DM was 2.98 per 1,000,000 child years, gradually increased over the study period, and there was no significant increase in T1DM with auto-antibody positivity in children and adolescents newly diagnosed from 2020-2022 in China compared with the previous 3 years. Furthermore, the frequency of DKA was peaked in 2020, and were not significantly different between patients who were negative vs. positive for auto-antibodies.

Challenges in achieving adequate glycemic control among children with type 1 diabetes mellitus in a resource-limited setting: A cross-sectional study from Sudan.

OBJECTIVE: To assess glycemic control and associated factors in children with type 1 diabetes mellitus (T1DM) attending the pediatric diabetes clinic in Wad-Madani City, Sudan. METHODS: This cross-sectional observational study was conducted at a referral center in Sudan. The study population consisted of children aged 1-18 years who had been diagnosed with T1DM for more than 1 year and were under regular follow-up in the clinic. Data on their glycemic control and sociodemographic and clinical characteristics were captured. RESULTS: Out of 211 enrolled patients, 120 (56.9 %) were females. The mean age was 11.7 years (SD = 4.0), with the mean age at diagnosis of 6.7 years (SD = 4.0). Only 6.2 % achieved adequate glycemic control. Adolescents had particularly poor control (97.8 %). The mean glycosylated hemoglobin (HBA1c) level was 10.4 % (90 mmol/mol). Inferior glycemic control was associated with advancing age, older age at diagnosis, belonging to single-parent households, less frequent self-monitoring of blood glucose (SMBG), and having a greater number of siblings or household members. A third of patients (33.8 %) had had one or more diabetes ketoacidosis (DKA) episodes in the previous year. There was a high prevalence of lipodystrophy (34.1 %) and arthropathy (25.1 %). CONCLUSIONS: An exceptionally low proportion of children with T1DM achieved adequate glycemic control, with adolescents particularly struggling. SMBG frequency and family dynamics emerged as potential factors, highlighting the urgent need for tailored interventions and improved diabetes education in resource-limited settings.

Liver, renal, genitourinary and diabetic ketoacidosis risks among new users of empagliflozin versus dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes: Post-authorization safety study based on multinational cohorts.

AIM: To estimate risks of diabetic ketoacidosis (DKA), acute liver injury (ALI), acute kidney injury (AKI), chronic kidney disease (CKD), severe complications of urinary tract infection (UTI) and genital infection (GI) among patients with type 2 diabetes initiating empagliflozin versus those initiating a dipeptidyl peptidase-4 (DPP-4) inhibitor. MATERIALS AND METHODS: In this large multinational, observational, new-user cohort study in UK, Danish and US healthcare data sources, patients initiated empagliflozin or a DPP-4 inhibitor between August 2014 and August 2019, were aged ≥18 years, and had ≥12 months' continuous health plan enrolment. Incidence rates by exposure and incidence rate ratios, adjusted for propensity-score deciles, were calculated. RESULTS: In total, 64 599 empagliflozin initiators and 203 315 DPP-4 inhibitor initiators were included. There was an increased risk [pooled adjusted incidence rate ratios (95% confidence interval)] of DKA [2.19 (1.74-2.76)] and decreased risks of ALI [0.77 (0.50-1.19) in patients without predisposing conditions of liver disease; 0.70 (0.56-0.88) in all patients] and AKI [0.54 (0.41-0.73)]. In the UK data, there was an increased risk of GI [males: 4.04 (3.46-4.71); females: 3.24 (2.81-3.74)] and decreased risks of CKD [0.53 (0.43-0.65)] and severe complications of UTI [0.51 (0.37-0.72)]. The results were generally consistent in subgroup and sensitivity analyses. CONCLUSIONS: Compared with DDP-4 inhibitor use, empagliflozin use was associated with increased risks of DKA and GI and decreased risks of ALI, AKI, CKD and severe complications of UTI. These associations are consistent with previous studies and known class effects of sodium-glucose cotransporter 2 inhibitors, including renoprotective effects and beneficial effects on alanine aminotransferase levels.

Rates of diabetic ketoacidosis with empagliflozin use during hospitalization for acute heart failure.

There is concern that sodium-glucose cotransporter-2 inhibitors during hospitalization for acute heart failure (aHF) may precipitate diabetic ketoacidosis (DKA). A retrospective study of all hospitalization encounters for aHF defined by a primary HF International Classification of Diseases (ICD)-10 code in 15 Kaiser Permanente Southern California medical centers hospitalized between January 1, 2021 and August 31, 2023 was performed to describe rates of DKA with empagliflozin use. DKA was defined by the presence of either a DKA ICD-10 code or ketoacidosis lab criteria (bicarbonate <18 mmol/L and urine ketone 1+ or more or elevated serum beta-hydroxybutyrate within 12 h) during hospitalization. Among 21,630 hospital encounters (15,518 patients) for aHF, 1678 (8%) had empagliflozin use. There were 2 (0.1%) probable DKA cases in empagliflozin encounters and 15 (0.1%) in nonexposed encounters. These rates were similar when stratified by diabetes status and ejection fraction. Empagliflozin may be safe during aHF hospitalization.

Associations Between Postdischarge Care and Cognitive Impairment-Related Hospital Readmissions for Ketoacidosis and Severe Hypoglycemia in Adults With Diabetes.

OBJECTIVE: Patients with severe hypoglycemia (SH) or diabetic ketoacidosis (DKA) experience high hospital readmission after being discharged. Cognitive impairment (CI) may further increase the risk, especially in those experiencing an interruption of medical care after discharge. This study examined the effect modification role of postdischarge care (PDC) on CI-associated readmission risk among U.S. adults with diabetes initially admitted for DKA or SH. RESEARCH DESIGN AND METHODS: We used the Nationwide Readmissions Database (NRD) (2016-2018) to identify individuals hospitalized with a diagnosis of DKA or SH. Multivariate Cox regression was used to compare the all-cause readmission risk at 30 days between those with and without CI identified during the initial hospitalization. We assessed the CI-associated readmission risk in the patients with and without PDC, an effect modifier with the CI status. RESULTS: We identified 23,775 SH patients (53.3% women, mean age 65.9 ± 15.3 years) and 140,490 DKA patients (45.8% women, mean age 40.3 ± 15.4 years), and 2,675 (11.2%) and 1,261 (0.9%), respectively, had a CI diagnosis during their index hospitalization. For SH and DKA patients discharged without PDC, CI was associated with a higher readmission risk of 23% (adjusted hazard ratio [aHR] 1.23, 95% confidence interval 1.08-1.40) and 35% (aHR 1.35, 95% confidence interval 1.08-1.70), respectively. However, when patients were discharged with PDC, we found PDC was an effect modifier to mitigate CI-associated readmission risk for both SH and DKA patients (P < 0.05 for all). CONCLUSIONS: Our results suggest that PDC can potentially mitigate the excessive readmission risk associated with CI, emphasizing the importance of postdischarge continuity of care for medically complex patients with comorbid diabetes and CI.

The risk factors of diabetic ketosis and diabetic ketoacidosis among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors: a retrospective study.

BACKGROUND: There is limited evidence on the safety of sodium-glucose co-transporter-2 inhibitor (SGLT2i) use in the real world of China. We conducted this two-center, retrospective study to assess the incidence rate and risk factors of Dapagliflozin-associated DK/DKA among patients with type 2 diabetes mellitus (T2DM) in China. RESEARCH DESIGN AND METHODS: Patients with T2DM treated with Dapagliflozin in Shanghai General Hospital were included in this retrospective analysis. Univariate and multivariate logistic regression was performed, and odds ratio (OR) and 95% confidence interval (CI) were calculated to identify the influencing factors associated with the occurrence of DK/DKA. RESULTS: A total of 1985 T2DM patients received Dapagliflozin for the first time were included. The prevalence of DK and DKA was 2.47% and 0.35%, respectively. Multivariate logistic regression identified age <45 years [OR = 2.99, 95% CI (1.45-6.17)], concomitant use of Acarbose [OR = 2.18, 95% CI (1.06-3.38)], Metformin [OR = 1.84, 95% CI (1.01-3.38)], and Insulin [OR = 1.93, 95% CI (1.02-3.66)] as participating factors for DK/DKA. The 1:4 matched subset sensitivity analysis further confirmed the risk factors of Dapagliflozin-associated DK/DKA. CONCLUSIONS: Age less than 45 years, concomitant use of Acarbose and insulin were risk factors for Dapagliflozin-associated DK/DKA. Clinicians should watch out for high-risk features among patients with SGLT2i prescription.

Prevalence of sodium-glucose transporter 2 inhibitor-associated diabetic ketoacidosis in real-world data: A systematic review and meta-analysis.

BACKGROUND: The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of diabetic ketoacidosis (DKA). As more drugs of this class are approved and their indications are expanded, this serious adverse effect has been increasingly reported. OBJECTIVE: This review evaluated observational studies to inform the prevalence of SGLT2-inhibitor-associated DKA compared with other antihyperglycemic agents. METHODS: A systematic review was conducted in PubMed and EMBASE until 19 July 2022 (PROSPERO: CRD42022385425). We included published retrospective cohort active comparator/new user (ACNU) and prevalent new user studies assessing SGLT2-inhibitor-associated DKA prevalence in adult patients with type 2 diabetes mellitus (T2DM) against active comparators. We excluded studies which lacked 1:1 propensity score matching. The JBI Checklist for Cohort Studies guided the risk-of-bias assessments. Meta-analysis was conducted based on the inverse variance method in R software. RESULTS: Sixteen studies with a sample of 2,956,100 nonunique patients met the inclusion criteria. Most studies were conducted in North America (n = 9) and adopted the ACNU design (n = 15). Meta-analysis of 14 studies identified 33% higher DKA risk associated with SGLT2 inhibitors (HR = 1.33, 95% CI: 1.14-1.55, P < 0.01). Meta-regression analysis identified the study location (P = 0.02), analysis principle (P < 0.001), exclusion of chronic comorbidities (P = 0.007), and canagliflozin (P = 0.04) as significant moderator variables. CONCLUSIONS: Despite limitations related to heterogeneity, generalizability, and misclassification, the results of this study show that SGLT2 inhibitors increase the prevalence of DKA among adult T2DM patients in the real world. The findings supplement evidence from randomized controlled trials (RCTs) and call for continued vigilance.

Sodium-glucose cotransporter-2 inhibitors for hypergycemia in phosphoinositide 3-kinase pathway inhibition.

PURPOSE: Phosphoinositide 3-kinase (PI3K) inhibition is used for the treatment of certain cancers, but can cause profound hyperglycemia and insulin resistance, for which sodium-glucose cotransporter-2 (SGLT2) inhibitors have been proposed as a preferred therapy. The objective of this research is to assess the effectiveness and safety of SGLT2 inhibitors for hyperglycemia in PI3K inhibition. METHODS: We conducted a single-center retrospective review of adults initiating the PI3K inhibitor alpelisib. Exposure to different antidiabetic drugs and adverse events including diabetic ketoacidosis (DKA) were assessed through chart review. Plasma and point-of-care blood glucoses were extracted from the electronic medical record. Change in serum glucose and the rate of DKA on SGLT2 inhibitor versus other antidiabetic drugs were examined as co-primary outcomes. RESULTS: We identified 103 patients meeting eligibility criteria with median follow-up of 92 days after starting alpelisib. When SGLT2 inhibitors were used to treat hyperglycemia, they were associated with a decrease in mean random glucose by -46 mg/dL (95% CI - 77 to - 15) in adjusted linear modeling. Five cases of DKA were identified, two occurring in patients on alpelisib plus SGLT2 inhibitor. Estimated incidence of DKA was: alpelisib plus SGLT2 inhibitor, 48 DKA cases per 100 patient-years (95% CI 6, 171); alpelisib with non-SGLT2 inhibitor antidiabetic drugs, 15 (95% CI 2, 53); alpelisib only, 4 (95% CI 0.1, 22). CONCLUSIONS: SGLT2 inhibitors are effective treatments for hyperglycemia in the setting of PI3K inhibition.

Real-World Use of Control-IQ Technology Is Associated with a Lower Rate of Severe Hypoglycemia and Diabetic Ketoacidosis Than Historical Data: Results of the Control-IQ Observational (CLIO) Prospective Study.

Objective: Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) remain significant risks with intensive insulin therapy. While these adverse event (AE) rates are generally very low in advanced hybrid closed-loop (AHCL) clinical studies, prospectively collected real-world AE rates are lacking. Research Design and Methods: The Control-IQ Observational (CLIO) study was a single-arm, prospective, longitudinal, postmarket surveillance study of individuals with type 1 diabetes (T1D) age 6 years and older who began the use of t:slim X2 insulin pump with Control-IQ technology in the real-world outpatient setting. AEs were reported monthly over 12 months and were compared to historical data from the T1D Exchange. Patient-reported outcomes were assessed quarterly. All study visits were virtual. Results: Three thousand one hundred fifty-seven participants enrolled from August 2020 through March 2022. Two thousand nine hundred ninety-eight participants completed through 12 months. SH rates were significantly lower than historic rates for children (9.31 vs. 19.31 events/100 patient years, d = 0.29, P < 0.01) and adults (9.77 vs. 29.49 events/100 patient years, d = 0.53, P < 0.01). DKA rates were also significantly lower in both groups. Lower observed rates of AEs occurred independent of baseline hemoglobin A1c or prior insulin delivery method. Time in range 70-180 mg/dL was 70.1% (61.0-78.8) for adults, 61.2% (52.4-70.5) for age 6-13, 60.9% (50.1-71.8) for age 14-17, and 67.3% (57.4-76.9) overall. Reduction in diabetes burden was consistently reported. Conclusions: SH and DKA rates were lower for users of t:slim X2 with Control-IQ technology compared to historical data for both adults and children. Real-world use of this AHCL system proved safe and effective in this virtual study design. The study was registered at clinicaltrials.gov (NCT04503174).

Paediatric diabetes-related presentations to emergency departments in Victoria, Australia from 2008 to 2018.

OBJECTIVES: Despite significant treatment advances in paediatric diabetes management, ED presentations for potentially preventable (PP) complications such as diabetic ketoacidosis (DKA) remains a major issue. We aimed to examine the characteristics, rates and trends of diabetes-related ED presentations and subsequent admissions in youth aged 0-19 years from 2008 to 2018. METHODS: Data were obtained from the Victorian Emergency Minimum Dataset and the National Diabetes Register. A diabetes-related ED presentation is defined using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification diagnosis codes. 'Non-preventable' presentations were the number of youths with newly diagnosed diabetes, and the remaining are classified as PP diabetes-related presentations. Poisson regression model was used to examine the trends in incidence rate and prevalence. RESULTS: Four thousand eight hundred and seventy-two (59%) of 8220 presentations were PP, 4683 (57%) were for DKA whereas 6200 (82%) required hospital admission. Diabetes-related ED presentations decreased from 38.4 to 27.5 per 100 youth with diabetes per year between 2008 and 2018 (ß = -0.04; confidence interval [CI] -0.04 to -0.03; P < 0.001). Females, those aged 0-4 years and rural youth had higher rates of ED presentations than males, older age groups and metropolitan youth. DKA presentations decreased from 20.1 presentations per 100 youth with diabetes in 2008-2009 to 14.9 presentations per 100 youth with diabetes in 2017-2018. The rate of DKA presentations was 68% higher in rural areas compared to metropolitan areas (incidence rate ratio 1.68; CI 1.59-1.78; P < 0.001). CONCLUSIONS: Although the rates of diabetes-related ED presentations declined, PP diabetes-related presentations and subsequent hospitalisation remain high. Patient level research is required to understand the increased DKA presentations in rural youth.

Open-source Artificial Pancreas Systems Are Safe and Effective When Supported In-clinic: Outcomes in 248 Consecutive Type 1 Diabetes Clients.

OBJECTIVE: Our aim in this study was to determine the safety, glycemia, and quality of life (QoL) associated with in-clinic installation and management of supported open-source artificial pancreas systems (SOSAPS) in type 1 diabetes (T1D). METHODS: This investigation is a retrospective cohort study of consecutive SOSAPS users at a Canadian diabetes centre. SOSAPS were offered to all moderately tech-savvy T1D clients on sensor-augmented multiple daily injection or pump, able to pay for hardware, and willing to sign a consent and waiver document. SOSAPS were installed and maintained by clinic staff at no cost to clients. iPhone users were assigned to either Loop (n=108) or iPhone artificial pancreas systems (iAPS; n=114) and Android users to Android-type APS (n=24). Outcomes included severe hypoglycemia and diabetic ketoacidosis (DKA), time in range (TIR) 4.0 to 10.0 mmol/L, time below range (TBR) <4 mmol/L, glucose management indicator (GMI), mean sensor glucose (MSG), change in glycated hemoglobin (A1C), and QoL. RESULTS: Two hundred forty-eight subjects (131 males, 117 females), with a mean age of 36 years and diabetes duration of 21 years, experienced 3 episodes of severe hypoglycemia and no DKA over a follow-up of 17 months. TIR rose by 16%, from 64% to 80% (p<0.0001); TBR fell by 1.0%, from 3.5% to 2.5% (p=0.001); MSG fell from 9.0 to 8.1 mmol/L (p<0.001); GMI fell from 7.3% to 6.7% (p<0.001); and A1C fell from 7.2% to 6.7% (p<0.0001). QoL scores were healthy before and improved after SOSAPS. CONCLUSIONS: Clients with T1D using SOSAPS and supported with no-cost care to the client (software, technology, and physician/physician assistant) safely achieved improved TIR, GMI, A1C, and QoL.

Association of Diabetic Ketoacidosis in Childhood New-Onset Type 1 Diabetes With Day of Presentation in Germany.

OBJECTIVE: Whether the day of the week on which the child presents affects timely diagnosis and risk of diabetic ketoacidosis (DKA) in children with new-onset type 1 diabetes (T1D) is not known. RESEARCH DESIGN AND METHODS: We used data of 30,717 children with new-onset T1D during the last 10 years from the German Prospective Diabetes Registry. We determined the odds ratios of T1D diagnosis and DKA on a weekday, public holiday, and school vacation. RESULTS: Compared with workdays, the odds ratios of being diagnosed with T1D were lower on weekends (0.39 [95% CI, 0.38-0.41]), public holidays (0.57 [0.53-0.63]), and school vacations (0.83 [0.80-0.85]). The odds of DKA diagnosis were also reduced on weekends (0.55 [0.52-0.59]), public holidays (0.73 [0.63-0.84]), and school vacations (0.85 [0.80-0.90]). Results did not change during the coronavirus 2019 pandemic. CONCLUSIONS: New-onset T1D and DKA in children are more often diagnosed during weekdays than weekends and holidays.