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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 -
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 -
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 -
British Journal of Anaesthesia Jul 2019Perioperative diabetic ketoacidosis (DKA) with near-normal blood glucose concentrations, termed euglycaemic ketoacidosis (EDKA), is an adverse effect associated with...
BACKGROUND
Perioperative diabetic ketoacidosis (DKA) with near-normal blood glucose concentrations, termed euglycaemic ketoacidosis (EDKA), is an adverse effect associated with sodium-glucose co-transporter-2 inhibitors (SGLT2i). Guidelines are still evolving concerning the perioperative management of patients on SGLT2i. We performed a systematic review of published reports of DKA from SGLT2i in the surgical setting to understand better the clinical presentation and characteristics of SGLT2i-associated DKA.
METHODS
We searched PubMed, Embase, and ProQuest for reports of perioperative DKA involving SGLT2i up to January 2019.
RESULTS
Forty-two reports of EDKA and five cases of hyperglycaemic diabetic ketoacidosis (HDKA) were identified from 33 publications. Canagliflozin was implicated in 26 cases. Presentation time varied from a few hours up to 6 weeks after operation. Precipitating factors may include diabetes medication changes, diet modifications, and intercurrent illnesses. There were 13 cases (12 EDKA and one HDKA) of bariatric surgery, 10 of them noted very-low-calorie diet regimes as a precipitating factor. No precise association between interruption of SGLT2i and the occurrence of DKA could be identified. Seven patients required mechanical ventilation, and acute kidney injury was noted in five. Five cases needed imaging to rule out anastomotic leak and pulmonary embolism, all of them revealed negative findings. Outcome data were available in 32 cases, all of them recovered completely.
CONCLUSIONS
EDKA is likely to be under-recognised because of its atypical presentation and may delay the diagnosis. Understanding this clinical entity, vigilance towards monitoring plasma/capillary ketones helps in early identification and assists in the management.
Topics: Diabetic Ketoacidosis; Humans; Intraoperative Complications; Postoperative Complications; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 31060732
DOI: 10.1016/j.bja.2019.03.028 -
Diabetic Medicine : a Journal of the... Jan 2018The aim of this systematic review was to examine the associations of individual-level as well as area-level socio-economic status and area-level deprivation with... (Review)
Review
Inequalities in glycaemic control, hypoglycaemia and diabetic ketoacidosis according to socio-economic status and area-level deprivation in Type 1 diabetes mellitus: a systematic review.
AIM
The aim of this systematic review was to examine the associations of individual-level as well as area-level socio-economic status and area-level deprivation with glycaemic control, hypoglycaemia and diabetic ketoacidosis in people with Type 1 diabetes mellitus.
METHODS
Ovid MEDLINE was searched to identify relevant cohort, case-control or cross-sectional studies published between January 2000 and June 2015. Search results were screened by title, abstract and keywords to identify eligible publications. Decisions on inclusion or exclusion of full texts were made independently by two reviewers. The Newcastle-Ottawa Scale was used to estimate the methodological quality of included studies. Quality assessment and extracted data of included studies were synthesized narratively and reported according to the PRISMA statement.
RESULTS
Literature search in Ovid MEDLINE identified 1345 eligible studies. Twenty studies matched our inclusion and exclusion criteria. Two articles were additionally identified through hand search. According to the Newcastle-Ottawa Scale, most of the studies were of average quality. Results on associations of socio-economic status and area-level deprivation with glycaemic control and hypoglycaemia were contradictory between studies. By contrast, lower socio-economic status and higher area-level deprivation were associated with a higher risk for diabetic ketoacidosis in all except one study.
CONCLUSIONS
Lower socio-economic status and higher area-level deprivation are associated with a higher risk of experiencing diabetic ketoacidosis in people with Type 1 diabetes mellitus. Access to care for socially deprived people needs to be expanded to overcome impairing effects on the course of the condition and to reduce healthcare disparities.
Topics: Blood Glucose; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glycated Hemoglobin; Health Status Disparities; Healthcare Disparities; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Social Class
PubMed: 28945942
DOI: 10.1111/dme.13519 -
BMC Endocrine Disorders May 2019Simultaneous development of thyroid storm and diabetic ketoacidosis (DKA) is a rare condition. The review aims to summarise its clinical presentation, investigation...
BACKGROUND
Simultaneous development of thyroid storm and diabetic ketoacidosis (DKA) is a rare condition. The review aims to summarise its clinical presentation, investigation findings and treatment options.
METHODS
Databases and reference lists of the selected articles were searched for case reports in English which describe concurrent presentation of thyroid storm and diabetic ketoacidosis. CARE guidelines were used for the quality assessment of the selected articles.
RESULTS
Twenty-six cases from twenty-one articles were selected out of 198 search results. Western Pacific, and American regions contributed to 77% of the cases. Females were most affected (88%). Features of Graves' disease like hyperthermia and tachycardia, gastrointestinal and neuro-psychiatric disturbances were the common clinical presentations. In most of the cases, previous diagnosis of diabetes mellitus preceded that of Graves' disease (46%). Among patients having their drug compliance reported, all had poor compliance to their routine anti-thyroid (9/9) and anti-diabetic (2/2) agents. Moreover, in all cases where HbA (7/7) and T4 (16/16) were measured, the results were elevated and where TSH (17/17) was measured, the results were low. The recommended treatment for DKA and thyroid storm was used in most cases and methimazole was the thionamide of choice in the latest four cases reported. All cases survived except four (15%).
CONCLUSIONS
Concurrent presentation of thyroid storm and diabetic ketoacidosis is rare but life-threatening. Therefore, efforts should be made to maximise patient compliance to anti-thyroid and anti-diabetic agents in treating such patients.
Topics: Diabetic Ketoacidosis; Humans; Meta-Analysis as Topic; Prognosis; Thyroid Crisis
PubMed: 31101104
DOI: 10.1186/s12902-019-0374-3