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Frontiers in Pharmacology 2023This study aimed to investigate the association between the use of sodium-glucose transporter 2 inhibitors (SGLT-2i) and the risk of diabetic ketoacidosis (DKA), lower...
This study aimed to investigate the association between the use of sodium-glucose transporter 2 inhibitors (SGLT-2i) and the risk of diabetic ketoacidosis (DKA), lower limb amputation (LLA), urinary tract infections (UTI), genital tract infections (GTI), bone fracture, and hypoglycemia in cohort studies. A systematic search was conducted in the PubMed and Embase databases to identify cohort studies comparing the safety of SGLT-2i versus other glucose-lowering drugs (oGLD) in patients with type 2 diabetes mellitus (T2DM). The quality of the studies was assessed using the Newcastle-Ottawa Scale. Primary endpoints were DKA and LLA, while secondary endpoints included UTI, GTI, bone fracture, and hypoglycemia. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. A total of 9,911,454 patients from 40 cohort studies were included in the analysis. SGLT-2i use was associated with a higher risk of DKA (HR: 1.21, 95% CI: 1.07-1.38, = 0.003) and GTI (HR: 2.72, 95% CI: 2.48-2.98, < 0.01). However, it was not associated with an increased risk of LLA (HR: 1.06, 95% CI: 0.92-1.23, = 0.42), UTI (HR: 0.99, 95% CI: 0.89-1.10, = 0.83), or bone fracture (HR: 0.99, 95% CI: 0.94-1.04, = 0.66). Furthermore, SGLT-2i was associated with a reduced risk of hypoglycemia. Furthermore, compared to dipeptidyl peptidase 4 inhibitors, SGLT-2i as a class and individually was associated with an increased risk of DKA. Canagliflozin specifically increased the risk of LLA (HR: 1.19, 95% CI: 1.04-1.36, = 0.01). The subgroup analysis suggested that SGLT-2i increased the risk of LLA among patients with a history of cardiovascular disease. SGLT-2i versus oGLD was associated with a similar occurrence of LLA, UTI, and bone fracture. However, SGLT-2i was associated with a higher risk of DKA and GTI than oGLD. These findings provide valuable information on the safety profile of SGLT-2i in patients with T2DM and can help inform clinical decision-making.
PubMed: 37905204
DOI: 10.3389/fphar.2023.1275060 -
Pediatric Nephrology (Berlin, Germany) Jul 2023One-third of children with type 1 diabetes mellitus manifest with diabetic ketoacidosis (DKA). Most children presenting with DKA are in a volume-depleted state, leading... (Review)
Review
BACKGROUND
One-third of children with type 1 diabetes mellitus manifest with diabetic ketoacidosis (DKA). Most children presenting with DKA are in a volume-depleted state, leading to acute kidney injury (AKI). Besides volume depletion, hyperglycemia can induce tubular injury and kidney inflammation. Therefore, a thorough knowledge of incidence of AKI, risk factors, and outcomes in pediatric DKA is desirable to improve its management and outcomes.
OBJECTIVE
To synthesize currently available evidence on the incidence, risk factors, and outcomes of AKI in children with DKA.
DATA SOURCES
We searched three electronic databases (EMBASE, PubMed, and Web of Science) from inception to September 2022 for original studies reporting AKI in children with DKA. Search strategies for the individual databases were drafted using free text words and MeSH incorporating "acute kidney injury" and "diabetic ketoacidosis."
STUDY ELIGIBILITY CRITERIA
Cohort and cross-sectional studies reporting AKI in children with type 1 DM and DKA were included.
PARTICIPANTS AND INTERVENTIONS
Children (aged less than 18 years) with type 1 DM and DKA.
STUDY APPRAISAL AND SYNTHESIS METHODS
The critical appraisal tool of NHLBI for cohort studies was used to assess the quality of the studies. We estimated the pooled incidence of AKI with 95% CI in children with DKA using a random effects model. The primary outcome was the pooled incidence of AKI during the DKA episodes.
RESULTS
Twenty-one studies assessing 4087 children (4500 DKA episodes) reported AKI during DKA episodes. The pooled incidence of any stage of AKI during the DKA episode was 47% (95% CI: 40 to 55). Severe AKI was observed in 28% (21 to 35) of DKA episodes; however, only 4% (1 to 11%) of children with AKI received dialysis. Low serum bicarbonate, low corrected sodium, higher blood sugar, and high blood urea nitrogen at presentation have been reported to be associated with the development of AKI.
CONCLUSION
AKI developed in almost half of the DKA episodes, and every fourth DKA episode was associated with severe AKI. The recovery rate from DKA-associated AKI appears to be high; however, further studies are needed to assess the exact impact of AKI on long-term outcomes.
REGISTRATION
PROSPERO (CRD42022303200). A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Humans; Child; Diabetic Ketoacidosis; Incidence; Cross-Sectional Studies; Renal Dialysis; Diabetes Mellitus, Type 1; Acute Kidney Injury; Hyperglycemia; Kidney; Retrospective Studies
PubMed: 36705755
DOI: 10.1007/s00467-023-05878-1 -
Diabetes Research and Clinical Practice Jan 2024This systematic review aims to provide evidence on effectiveness of interventions used in emergency care of hypoglycaemia and diabetic ketoacidosis (DKA). (Review)
Review
AIM
This systematic review aims to provide evidence on effectiveness of interventions used in emergency care of hypoglycaemia and diabetic ketoacidosis (DKA).
METHODOLOGY
This is a systematic review of randomized controlled trials and analytical studies. We selected studies based on eligibility criteria. The databases Medline, Cochrane library and Embase were searched from their inception till November 2, 2022, using search strategy. We used the term such as "diabetes mellitus", "treatment", "hypoglycaemia", "diabetic ketoacidosis", "low blood sugar", "high blood sugar" and Mesh terms like "disease management", "hypoglycaemia", "diabetic ketoacidosis", and "diabetes mellitus" to form search strategy.
RESULTS
Hypoglycemia: Both 10 % dextrose (D10) and 50 % dextrose (D50) are effective options with similar hospital mortality D10 (4.7 %) and D50 (6.2 %). DKA: Low dose insulin is non-inferior to standard dose with time till resolution of DKA 16.5 (7.2) hours and 17.2 (7.7) hours (p value = 0.73) respectively. In children, subcutaneous insulin was associated with reduced ICU admissions and hospital readmissions (67.8 % to 27.9 %). Plasmalyte (PL) is noninferior to sodium chloride (SC), with ICU length of stay 49 h (IQR 23-72) and 55 h (IQR 41-80) respectively, hyperchloremia was associated with longer in-hospital length of stay and longer time to resolution of DKA. And potassium replacement at < 10 mmol/L was associated with higher mortality (n = 72).
CONCLUSION
We conclude either of the 10 % or 50 % dextrose is effective for management of hypoglycaemia. For DKA subcutaneous insulin and intravenous insulin, chloride levels ≤ 109 mEq/L, potassium above 10 mmol/l, IV fluids like Plasmalyte and normal saline are effective.
Topics: Child; Humans; Diabetic Ketoacidosis; Blood Glucose; Hypoglycemia; Insulin; Emergency Medical Services; Insulin, Regular, Human; Potassium; Diabetes Mellitus
PubMed: 38154537
DOI: 10.1016/j.diabres.2023.111078 -
Frontiers in Pharmacology 2023Sodium-glucose cotransporter-2 (SGLT2) inhibitors have proven to be effective in improving glycemic control in patients with type 2 diabetes mellitus (T2DM). However,...
Sodium-glucose cotransporter-2 (SGLT2) inhibitors have proven to be effective in improving glycemic control in patients with type 2 diabetes mellitus (T2DM). However, the risk of diabetic ketoacidosis (DKA) in patients remains unclear. The purpose of this study is to conduct this systematic review and network meta-analysis for the risk of DKA of SGLT2 inhibitors in patients with T2DM. We searched for randomized controlled trials (RCTs) concerning SGLT2 inhibitors in patients with T2DM in PubMed, EMBASE (Ovid SP), Cochrane Central Register of Controlled Trials (Ovid SP), and ClinicalTrials.gov from inception to January 2022. The primary outcomes were the risk of DKA. We assessed the sparse network with a fixed-effect model and consistency model in a frequentist framework with a graph-theoretical method by the netmeta package in R. We assessed the evidence quality of evidence of outcomes according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). In total, 36 studies involving 52,264 patients were included. The network showed that there was no significant difference observed among SGLT2 inhibitors, other active antidiabetic drugs, and placebo in the risk of DKA. There was no significant difference in the DKA risk between different doses of SGLT2 inhibitors. The certainty of the evidence ranged from very low to moderate. The probabilities of rankings and P-score showed that compared to placebo, SGLT2 inhibitors might increase the risk of DKA (P-score = 0.5298). Canagliflozin might have a higher DKA risk than other SGLT2 inhibitors (P-score = 0.7388). Neither SGLT2 inhibitors nor other active antidiabetic drugs were associated with an increased risk of DKA compared to placebo, and the risk of DKA with SGLT2 inhibitors was not found to be dose-dependent. In addition, the use of canagliflozin was less advisable than other SGLT2 inhibitors according to the rankings and P-score. https://www.crd.york.ac.uk/prospero/, identifier PROSPERO, CRD42021297081.
PubMed: 37397500
DOI: 10.3389/fphar.2023.1145587 -
Critical Care Explorations Feb 2023In children with diabetic ketoacidosis (DKA), insulin infusions are the mainstay of treatment; however, optimal dosing remains unclear. Our objective was to compare the... (Review)
Review
UNLABELLED
In children with diabetic ketoacidosis (DKA), insulin infusions are the mainstay of treatment; however, optimal dosing remains unclear. Our objective was to compare the efficacy and safety of different insulin infusion doses for the treatment of pediatric DKA.
DATA SOURCES
We searched MEDLINE, EMBASE, PubMed, and Cochrane from inception to April 1, 2022.
STUDY SELECTION
We included randomized controlled trials (RCTs) of children with DKA comparing intravenous insulin infusion administered at 0.05 units/kg/hr (low dose) versus 0.1 units/kg/hr (standard dose).
DATA EXTRACTION
We extracted data independently and in duplicate and pooled using a random effects model. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development and Evaluation approach.
DATA SYNTHESIS
We included four RCTs ( = 190 participants). In children with DKA, low-dose compared with standard-dose insulin infusion probably has no effect on time to resolution of hyperglycemia (mean difference [MD], 0.22 hr fewer; 95% CI, 1.19 hr fewer to 0.75 hr more; moderate certainty), or time to resolution of acidosis (MD, 0.61 hr more; 95% CI, 1.81 hr fewer to 3.02 hr more; moderate certainty). Low-dose insulin infusion probably decreases the incidence of hypokalemia (relative risk [RR], 0.65; 95% CI, 0.47-0.89; moderate certainty) and hypoglycemia (RR, 0.37; 95% CI, 0.15-0.80; moderate certainty), but may have no effect on rate of change of blood glucose (MD, 0.42 mmol/L/hr slower; 95% CI, 1 mmol/L/hr slower to 0.18 mmol/L/hr faster; low certainty).
CONCLUSIONS
In children with DKA, the use of low-dose insulin infusion is probably as efficacious as standard-dose insulin, and probably reduces treatment-related adverse events. Imprecision limited the certainty in the outcomes of interest, and the generalizability of the results is limited by all studies being performed in a single country.
PubMed: 36844374
DOI: 10.1097/CCE.0000000000000857 -
Journal of Medical Virology Jun 2023Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents may increase risk for a variety of post-acute sequelae including... (Meta-Analysis)
Meta-Analysis
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents may increase risk for a variety of post-acute sequelae including new-onset type 1 diabetes mellitus (T1DM). Therefore, this meta-analysis aims to estimate the risk of developing new-onset type 1 diabetes in children and adolescents as post-acute sequelae of SARS-CoV-2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to March 20, 2023. A systematic review and subsequent meta-analyses were performed to calculate the pooled effect size, expressed as risk ratio (RR) with corresponding 95% confidence interval (CI) of each outcome based on a one-stage approach and the random-effects estimate of the pooled effect sizes of each outcome were generated with the use of the DerSimonian-Laird method. Eight reports from seven studies involving 11 220 530 participants (2 140 897 patients with a history of diagnosed SARS-CoV-2 infection and 9 079 633 participants in the respective control groups) were included. The included studies reported data from four U.S. medical claims databases covering more than 503 million patients (IQVIA, HealthVerity, TriNetX, and Cerner Real-World Data), and three national health registries for all children and adolescents in Norway, Scotland, and Denmark. It was shown that the risk of new-onset T1DM following SARS-CoV-2 infection in children and adolescents was 42% (95% CI 13%-77%, p = 0.002) higher compared with non-COVID-19 control groups. The risk of developing new-onset T1DM following SARS-CoV-2 infection was significantly higher (67%, 95% CI 32 %-112%, p = 0.0001) in children and adolescents between 0 and 11 years, but not in those between 12 and 17 years (RR = 1.10, 95% CI 0.54-2.23, p = 0.79). We also found that the higher risk for developing new-onset T1DM following SARS-CoV-2 infection only exists in studies from the United States (RR = 1.70, 95% CI 1.37-2.11, p = 0.00001) but not Europe (RR = 1.02, 95% CI 0.67-1.55, p = 0.93). Furthermore, we found that SARS-CoV-2 infection was associated with an elevation in the risk of diabetic ketoacidosis (DKA) in children and adolescents compared with non-COVID-19 control groups (RR = 2.56, 95% CI 1.07-6.11, p = 0.03). Our findings mainly obtained from US medical claims databases, suggest that SARS-CoV-2 infection is associated with higher risk of developing new-onset T1DM and diabetic ketoacidosis in children and adolescents. These findings highlight the need for targeted measures to raise public health practitioners and physician awareness to provide intervention strategies to reduce the risk of developing T1DM in children and adolescents who have had COVID-19.
Topics: Child; Humans; Adolescent; COVID-19; Diabetes Mellitus, Type 1; SARS-CoV-2; Diabetic Ketoacidosis; Post-Acute COVID-19 Syndrome; Cohort Studies
PubMed: 37264687
DOI: 10.1002/jmv.28833 -
Acta Psychiatrica Scandinavica May 2022Clozapine is substantially underutilized in most countries and clinician factors including lack of knowledge and concerns about adverse drug effects (ADEs) contribute... (Review)
Review
OBJECTIVE
Clozapine is substantially underutilized in most countries and clinician factors including lack of knowledge and concerns about adverse drug effects (ADEs) contribute strongly to treatment reluctance. The aim of this systematic review was to provide clinicians with a comprehensive information source regarding clozapine ADEs.
METHODS
PubMed and Embase databases were searched for English language reviews concerned with clozapine ADEs; publications identified by the automated search were manually searched for additional relevant citations. Following exclusion of redundant and irrelevant reports, pertinent information was summarized in evidence tables corresponding to each of six major ADE domains; two authors reviewed all citations for each ADE domain and summarized their content by consensus in the corresponding evidence table. This study was conducted in accordance with PRISMA principles.
RESULTS
Primary and secondary searches identified a total of 305 unique reports, of which 152 were included in the qualitative synthesis. Most clozapine ADEs emerge within 3 months, and almost all appear within 6 months, after initiation. Notable exceptions are weight gain, diabetic ketoacidosis (DKA), severe clozapine-induced gastrointestinal hypomotility (CIGH), clozapine-induced cardiomyopathy (CICM), seizures, and clozapine-induced neutropenia (CIN). Most clozapine ADEs subside gradually or respond to dose reduction; those that prompt discontinuation generally do not preclude rechallenge. Rechallenge is generally inadvisable for clozapine-induced myocarditis (CIM), CICM, and clozapine-induced agranulocytosis (CIA). Clozapine plasma levels >600-1000 μg/L appear more likely to cause certain ADEs (e.g., seizures) and, although there is no clear toxicity threshold, risk/benefit ratios are generally unfavorable above 1000 μg/L.
CONCLUSION
Clozapine ADEs rarely require discontinuation.
Topics: Antipsychotic Agents; Cardiomyopathies; Clozapine; Drug-Related Side Effects and Adverse Reactions; Humans; Myocarditis; Neutropenia; Seizures
PubMed: 35178700
DOI: 10.1111/acps.13406 -
Cureus Oct 2022The most common acute hyperglycemic emergency is diabetic ketoacidosis (DKA). DKA is one of the leading causes of Type 1 diabetes (T1D) related deaths in people aged 30... (Review)
Review
The most common acute hyperglycemic emergency is diabetic ketoacidosis (DKA). DKA is one of the leading causes of Type 1 diabetes (T1D) related deaths in people aged 30 and under. In this meta-analysis, the Overall use of IV insulin in patients with mild/moderate vs. severe diabetic ketoacidosis was compared in randomized controlled trial articles from January 2011 to December 2021 using EMBASE, Medline, and CENTRAL. Only 8 of 3258 studies met the inclusion criteria. This review shows that intravenous insulin can significantly decrease plasma glucose and potassium levels in mild/moderate cases and severe cases. However, it can decrease the resolution time of acidosis more quickly in mild/moderate cases than in severe cases. In the current meta-analysis, the use of IV insulin is secure and efficient. There was no discernible difference in the effectiveness of IV insulin between mild/moderate and severe DKA.
PubMed: 36439560
DOI: 10.7759/cureus.30721 -
Journal of Clinical Pathology Mar 2023To examine the value of vitreous beta-hydroxybutyrate and serum acetone in the investigation of sudden unexpected death.
AIM
To examine the value of vitreous beta-hydroxybutyrate and serum acetone in the investigation of sudden unexpected death.
METHODS
Coroners' autopsy reports from a provincial UK city, with a population of approximately 900 000, over a 24-month period with significant ketoacidosis were studied. Demographic features, medical history, anatomical and histological findings, and biochemical parameters, including renal function, vitreous glucose, serum and vitreous alcohol, were analysed.
RESULTS
Forty-two cases (28 males and 14 females) were identified; 55% had a history of alcohol and/or substance misuse, and mental health problems, particularly depression and anxiety, and 16% were diabetic. In all, 50% of subjects had alcoholic ketoacidosis (AKA), 19% had diabetic ketoacidosis (DKA) and 12% had a history of both diabetes and alcohol abuse. In 19% of cases, an exact cause of ketoacidosis was established. In AKA, the subjects typically had low vitreous glucose and low or undetected blood alcohol levels. All of the subjects with raised vitreous glucose levels had DKA.
CONCLUSION
Ketoacidosis is relatively common and should be considered as a cause of sudden death, especially in alcoholic patients and patients with diabetes with no clear cause of death at autopsy.
Topics: Female; Humans; Male; Alcoholism; Autopsy; Diabetic Ketoacidosis; Glucose; Ketosis
PubMed: 34980639
DOI: 10.1136/jclinpath-2021-207681 -
Frontiers in Endocrinology 2023The safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain... (Comparative Study)
Comparative Study Meta-Analysis
Comparative safety of different recommended doses of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.
OBJECTIVE
The safety results of different recommended doses of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) for patients with type 2 diabetes mellitus (T2DM) remain uncertain. This study aims to comprehensively estimate and rank the relative safety outcomes with different doses of SGLT-2i for T2DM.
METHODS
PubMed, Embase, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese National Knowledge Infrastructure, WanFang database, and SinoMed database were searched from the inception to 31 May 2023. We included double-blind randomized controlled trials (RCTs) comparing SGLT-2i with placebo or another antihyperglycemic as oral monotherapy in the adults with a diagnosis of T2DM.
RESULTS
Twenty-five RCTs with 12,990 patients randomly assigned to 10 pharmacological interventions and placebo were included. Regarding genital infections (GI), all SGLT-2i, except for ertugliflozin and ipragliflozin, were associated with a higher risk of GI compared to placebo. Empagliflozin 10mg/d (88.2%, odds ratio [OR] 7.90, 95% credible interval [CrI] 3.39 to 22.08) may be the riskiest, followed by empagliflozin 25mg/d (83.4%, OR 7.22, 95%CrI 3.11 to 20.04)) and canagliflozin 300mg/d (70.8%, OR 5.33, 95%CrI 2.25 to 13.83) based on probability rankings. Additionally, dapagliflozin 10mg/d ranked highest for urinary tract infections (UTI, OR 2.11, 95%CrI 1.20 to 3.79, 87.2%), renal impairment (80.7%), and nasopharyngitis (81.6%) when compared to placebo and other treatments. No increased risk of harm was observed with different doses of SGLT-2i regarding hypoglycemia, acute kidney injury, diabetic ketoacidosis, or fracture. Further subgroup analysis by gender revealed no significantly increased risk of UTI. Dapagliflozin 10mg/d (91.9%) and canagliflozin 300mg/d (88.8%) ranked first in the female and male subgroups, respectively, according to the probability rankings for GI.
CONCLUSION
Current evidence indicated that SGLT-2i did not significantly increase the risk of harm when comparing different doses, except for dapagliflozin 10mg/d, which showed an increased risk of UTI and may be associated with a higher risk of renal impairment and nasopharyngitis. Additionally, compared with placebo and metformin, the risk of GI was notably elevated for empagliflozin 10mg/d, canagliflozin 300mg/d, and dapagliflozin 10mg/d. However, it is important to note that further well-designed RCTs with larger sample sizes are necessary to verify and optimize the current body of evidence.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023396023.
Topics: Female; Humans; Male; Canagliflozin; Diabetes Mellitus, Type 2; Glucose; Nasopharyngitis; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38027214
DOI: 10.3389/fendo.2023.1256548