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Clinical and Experimental Pediatrics Jun 2024Two rehydration protocols currently exist to treat diabetic ketoacidosis (DKA) in pediatric patients aged <21 years: the traditional "one-bag" system and the more recent...
Two rehydration protocols currently exist to treat diabetic ketoacidosis (DKA) in pediatric patients aged <21 years: the traditional "one-bag" system and the more recent "two-bag" system. This study aimed to evaluate the safety and efficacy of the newer two-bag system versus the well-established one-bag system. The CiNAHL, Cochrane Library, Embase, PubMed, Scopus, and Web of Science databases were comprehensively searched from inception to June 2023 by 2 independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis framework. Eligible studies were those that reported participants <21 years of age who presented to the emergency room with a clinical diagnosis of DKA. This review was prospectively registered on PROSPERO (CRD42023427551). From the initial screening of 42 studies, 8 unique studies encompassing 583 patients met the eligibility criteria. The analysis yielded no significant intergroup differences in hypoglycemia (odds ratio, 0.61; 95% confidence interval [CI], 0.20-1.87; I2=3%) or mean glucose correction rate (mean difference [MD], 0.04 mg/dL/hr; 95% CI, -13.10 to 13.17; I2=64%). The incidence of cerebral edema was as low (0.17%) across groups, with only one case reported in the one-bag group. Notably, the mean time to DKA resolution (MD, -3.24 h; 95% CI, -5.57 to -0.91; I2=0%) and mean response time for intravenous fluid changes (MD, -32.75 min; 95% CI, -43.21 to -22.29; I2=59%) was lower for the two-bag system. This meta-analysis presents preliminary evidence suggesting that the two-bag system may confer advantages over the one-bag system for selected patients. However, further studies with greater patient stratification based on DKA severity, fluid composition, and protocol are needed to draw definitive conclusions and elucidate the extent of these advantages.
PubMed: 38938043
DOI: 10.3345/cep.2023.01536 -
Frontiers in Endocrinology 2024The optimal resuscitative fluid for patients with diabetic ketoacidosis (DKA) remains controversial. Therefore, our objective was to assess the effect of balanced... (Meta-Analysis)
Meta-Analysis Comparative Study
PURPOSE
The optimal resuscitative fluid for patients with diabetic ketoacidosis (DKA) remains controversial. Therefore, our objective was to assess the effect of balanced crystalloids in contrast to normal saline on clinical outcomes among patients with DKA.
METHODS
We searched electronic databases for randomized controlled trials comparing balanced crystalloids versus normal saline in patients with DKA, the search period was from inception through October 20, 2023. The outcomes were the time to resolution of DKA, major adverse kidney events, post-resuscitation chloride, and incidence of hypokalemia.
RESULTS
Our meta-analysis encompassed 11 trials, incorporating a total of 753 patients with DKA. There was no significant difference between balanced crystalloids and normal saline group for the time to resolution of DKA (MD -1.49, 95%CI -4.29 to 1.31, P=0.30, I = 65%), major adverse kidney events (RR 0.88, 95%CI 0.58 to 1.34, P=0.56, I = 0%), and incidence of hypokalemia (RR 0.80, 95%CI 0.43 to 1.46, P=0.46, I = 56%). However, there was a significant reduction in the post-resuscitation chloride (MD -3.16, 95%CI -5.82 to -0.49, P=0.02, I = 73%) among patients received balanced crystalloids.
CONCLUSION
Among patients with DKA, the use of balanced crystalloids as compared to normal saline has no effect on the time to resolution of DKA, major adverse kidney events, and incidence of hypokalemia. However, the use of balanced crystalloids could reduce the post-resuscitation chloride.
SYSTEMATIC REVIEW REGISTRATION
https://osf.io, identifier c8f3d.
Topics: Humans; Diabetic Ketoacidosis; Crystalloid Solutions; Randomized Controlled Trials as Topic; Fluid Therapy; Saline Solution; Hypokalemia
PubMed: 38836222
DOI: 10.3389/fendo.2024.1367916 -
Diabetology & Metabolic Syndrome May 2024Cancer patients with diabetes are at increased risk for cardiovascular diseases due to common risk factors and well-documented drug-associated cardiotoxicity....
BACKGROUND
Cancer patients with diabetes are at increased risk for cardiovascular diseases due to common risk factors and well-documented drug-associated cardiotoxicity. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown cardiovascular benefits in patients with diabetes, but their effects on cancer patients remain unclear. This study aimed to evaluate the cardiovascular outcomes associated with SGLT2 inhibitor therapy in patients with concomitant diabetes and cancer.
METHODS
We conducted a systematic review and meta-analysis of cohort studies comparing cardiovascular outcomes between cancer patients with diabetes receiving SGLT2 inhibitors and those not receiving SGLT2 inhibitors. PubMed, Embase, and the Cochrane Library were searched from inception to February 29, 2024. The primary outcome was all-cause mortality, and the secondary outcomes were heart failure hospitalization, and adverse events. Random-effect models were used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and explore the effect of SGLT2 inhibitors on mitigating cardiotoxicity.
RESULTS
Nine cohort studies involving 82,654 patients were included. SGLT2 inhibitor use was associated with a significantly lower risk of all-cause mortality (RR 0.46, 95% CI 0.31-0.68, P < 0.0001; I = 98%) and heart failure hospitalization (RR 0.49, 95% CI 0.30-0.81, P = 0.006; I = 21%) compared to non-use. The mortality benefit remained significant in patients receiving anthracycline chemotherapy (RR 0.50, 95% CI 0.28-0.89, P = 0.02; I = 71%). SGLT2 inhibitor use was also associated with a lower risk of sepsis (RR 0.32, 95% CI 0.23-0.44, P < 0.00001; I = 0%) and no increased risk of diabetic ketoacidosis (RR 0.66, 95% CI 0.20-2.16, P = 0.49; I = 0%).
CONCLUSIONS
SGLT2 inhibitor therapy is associated with lower risks of all-cause mortality and heart failure hospitalization in patients with concomitant diabetes and cancer. These findings suggest that SGLT2 inhibitors may offer cardiovascular benefits in this high-risk population. Randomized controlled trials are needed to validate these findings and evaluate the safety and efficacy of SGLT2 inhibitors in specific cancer types and treatment regimens.
PubMed: 38773486
DOI: 10.1186/s13098-024-01354-4 -
Paediatric Drugs May 2024In adults, sodium-glucose cotransporter type 2 inhibitors have revolutionised the treatment of type 2 diabetes mellitus, heart failure, and chronic kidney disease.
INTRODUCTION
In adults, sodium-glucose cotransporter type 2 inhibitors have revolutionised the treatment of type 2 diabetes mellitus, heart failure, and chronic kidney disease.
OBJECTIVE
We aimed to review information on compassionate use, clinical pharmacology, efficacy, and safety of dapagliflozin and empagliflozin in children.
METHODS
We conducted a systematic review of published clinical trials, case reports, and observational studies in Medline, Excerpta Medica, and Web of Science databases from inception to September 2023. For the two randomised controlled trials on type 2 diabetes mellitus (T2DM), we implemented a meta-analysis on the primary outcome (mean difference in glycosylated haemoglobin [HbA1c] between intervention and placebo groups). Review Manager (RevMan), version 5.4.1, was used for this purpose.
RESULTS
Thirty-five articles (nine case reports, ten case series, one prospective non-controlled trial, four controlled randomised trials, two surveys, six pharmacokinetic studies, and three pharmacovigilance studies) were selected, in which 415 children were exposed to either dapagliflozin or empagliflozin: 189 diabetic patients (mean age 14.7 ± 2.9 years), 32 children with glycogen storage disease type Ib (GSD Ib), glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency, or severe congenital neutropenia type 4 (8.5 ± 5.1 years), 47 children with kidney disease or heart failure (11.2 ± 6.1 years), 84 patients in pharmacokinetic studies (15.1 ± 2.3 years), and 63 patients in toxicological series. The effect of dapagliflozin and empagliflozin in T2DM was demonstrated by HbA1c reduction in two randomised trials among a total of 177 adolescents, with a mean HbA1c difference of -0.82% (95% confidence interval -1.34 to -0.29) as compared to placebo (no heterogeneity, I = 0%). Dosage ranged between 5 and 20 mg (mean 11.4 ± 3.7) once daily for dapagliflozin and between 5 and 25 mg (mean 15.4 ± 7.4) once daily for empagliflozin. Among the paediatric cases of GSD Ib, empagliflozin 0.1-1.3 mg/kg/day improved neutropenia, infections, and gastrointestinal health. Dapagliflozin (mean dosage 6.9 ± 5.2 mg once daily) was well-tolerated in children with chronic kidney disease and heart failure. Side effects were generally mild, the most frequent being hypoglycaemia in children with GSD Ib (33% of patients) or T2DM (14% of patients) on concomitant hypoglycaemic drugs. Diabetic ketoacidosis is rare in children.
CONCLUSION
Early evidence suggests that dapagliflozin and empagliflozin are well tolerated in children. A clinical pharmacology rationale currently exists only for adolescents with diabetes mellitus.
PROSPERO REGISTRATION NUMBER
CRD42023438162.
Topics: Benzhydryl Compounds; Humans; Glucosides; Child; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Adolescent
PubMed: 38635113
DOI: 10.1007/s40272-024-00623-z -
Cureus Apr 2024As cancer continues to be the leading cause of death worldwide, additional therapeutic options other than traditional platinum-based chemotherapy have become available... (Review)
Review
As cancer continues to be the leading cause of death worldwide, additional therapeutic options other than traditional platinum-based chemotherapy have become available that target tumor cells in innovative ways. Immunotherapies (e.g., immune checkpoint inhibitors (ICI)) ramp up the immune system to target cancer cells, providing patients with more personalized and tumor cell-specific treatment options. This new age oncological treatment option has been found to provide a more meaningful and stronger alternative to traditional chemotherapy, resulting in longer periods of remission and milder side effects. However, because ICI heightens the immune system, resultant autoimmune conditions can occur. One of the most recently shown adverse effects of ICI are extreme hyperglycemia (i.e., type 1 diabetes) and diabetic ketoacidosis (DKA). To determine the incidence of immunotherapy-induced diabetes, a systematic literature review was performed using CINHAL, EBSCO, MEDLINE, and Web of Science. A total of 403 articles were initially screened, with a final 28 case reports included. The results show that checkpoint inhibitors were found to be most commonly associated with new-onset diabetes as opposed to traditional chemotherapy. Additionally, 41% of patients developed autoimmune diabetes and DKA after being placed on a single therapy of pembrolizumab (targets PD-1: programmed cell death protein 1). However, the pathological process underlying the development of endocrinopathies after treatment with ICI continues to be under investigation.
PubMed: 38606021
DOI: 10.7759/cureus.57894 -
Journal of Evidence-based Medicine Jun 2024To determine the comparative effectiveness of fluid schemes for children with diabetic ketoacidosis (DKA).
AIM
To determine the comparative effectiveness of fluid schemes for children with diabetic ketoacidosis (DKA).
METHODS
We conducted a systematic review with an attempt to conduct network meta-analysis (NMA). We searched MEDLINE, EMBASE, CENTRAL, Epistemonikos, Virtual Health Library, and gray literature from inception to July 31, 2022. We included randomized controlled trials (RCTs) in children with DKA evaluating any intravenous fluid schemes. We planned to conduct NMA to compare all fluid schemes if heterogeneity was deemed acceptable.
RESULTS
Twelve RCTs were included. Studies were heterogeneous in the population (patients and DKA episodes), interventions with different fluids (saline, Ringer's lactate (RL), and polyelectrolyte solution-PlasmaLyte), tonicity, volume, and administration systems. We identified 47 outcomes that measured clinical manifestations and metabolic control, including single and composite outcomes and substantial heterogeneity preventing statistical combination. No evidence was found of differences in neurological deterioration (main outcome), but differences were found among interventions in some comparisons to normalize acid-base status (∼2 h less with low vs. high volume); time to receive subcutaneous insulin (∼1 h less with low vs. high fluid rate); length of stay (∼6 h less with RL vs. saline); and resolution of the DKA (∼3 h less with two-bag vs. one-bag scheme). However, available evidence is scarce and poor.
CONCLUSIONS
There is not enough evidence to determine the best fluid therapy in terms of fluid type, tonicity, volume, or administration time for DKA treatment. There is an urgent need for more RCTs, and the development of a core outcome set on DKA in children.
Topics: Humans; Diabetic Ketoacidosis; Fluid Therapy; Child; Randomized Controlled Trials as Topic
PubMed: 38572835
DOI: 10.1111/jebm.12603 -
Endocrine Mar 2024SGLT-2i are increasingly recognized for their benefits in patients with cardiometabolic risk factors. Additionally, emerging evidence suggests potential applications in...
OBJECTIVE
SGLT-2i are increasingly recognized for their benefits in patients with cardiometabolic risk factors. Additionally, emerging evidence suggests potential applications in acute illnesses, including COVID-19. This systematic review aims to evaluate the effects of SGLT-2i in patients facing acute illness, particularly focusing on SARS-CoV-2 infection.
METHODS
Following PRISMA guidelines, a systematic search of PubMed, Scopus, medRxiv, Research Square, and Google Scholar identified 22 studies meeting inclusion criteria, including randomized controlled trials and observational studies. Data extraction and quality assessment were conducted independently.
RESULTS
Out of the 22 studies included in the review, six reported reduced mortality in DM-2 patients taking SGLT-2i, while two found a decreased risk of hospitalization. Moreover, one study demonstrated a lower in-hospital mortality rate in DM-2 patients under combined therapy of metformin plus SGLT-2i. However, three studies showed a neutral effect on the risk of hospitalization. No increased risk of developing COVID-19 was associated with SGLT-2i use in DM-2 patients. Prior use of SGLT-2i was not associated with ICU admission and need for MV. The risk of acute kidney injury showed variability, with inconsistent evidence regarding diabetic ketoacidosis.
CONCLUSION
Our systematic review reveals mixed findings on the efficacy of SGLT-2i use in COVID-19 patients with cardiometabolic risk factors. While some studies suggest potential benefits in reducing mortality and hospitalizations, others report inconclusive results. Further research is needed to clarify optimal usage and mitigate associated risks, emphasizing caution in clinical interpretation.
PubMed: 38448675
DOI: 10.1007/s12020-024-03758-8 -
Diabetes Research and Clinical Practice Mar 2024Studies suggested a higher prevalence of Attention-deficit/hyperactivity disorder (ADHD) in individuals with Type 1 Diabetes Mellitus (T1D). However, it is unclear how... (Meta-Analysis)
Meta-Analysis Review
AIMS
Studies suggested a higher prevalence of Attention-deficit/hyperactivity disorder (ADHD) in individuals with Type 1 Diabetes Mellitus (T1D). However, it is unclear how ADHD impacts glycemia and diabetes-related complications. This systematic review and meta-analysis aimed to investigate the effect of ADHD and ADHD medications on HbA1c and acute complications in T1D.
METHODS
A literature search was conducted in PubMed, EMBASE, CINAHL, Scopus, PsycINFO, CENTRAL, and Web of Science collections up to November 22, 2023. Seventeen studies were selected for the systematic review by independent reviewers, with twelve included in the meta-analysis.
RESULTS
Mean HbA1c levels were significantly higher in T1D individuals with ADHD compared to those without ADHD (MD = 0.60; 95 % CI: 0.41, 0.79; I = 90.1 %; p-value < 0.001). The rates of suboptimal HbA1c levels, hospitalization, diabetic ketoacidosis, and hypoglycemia were all substantially higher in T1D individuals with ADHD than those without ADHD. No difference was found in mean HbA1c between those who received ADHD treatment and those who did not (mean difference = -0.52; 95 % confidence interval: -1.16, 0.13; I = 78.6 %; p-value = 0.12).
CONCLUSIONS
ADHD is associated with higher HbA1c and increased acute diabetes-related complications. More research is needed to assess the effects of ADHD treatments on T1D management.
Topics: Humans; Diabetes Mellitus, Type 1; Attention Deficit Disorder with Hyperactivity; Glycated Hemoglobin; Hypoglycemia; Diabetic Ketoacidosis
PubMed: 38360095
DOI: 10.1016/j.diabres.2024.111566 -
BMJ Open Feb 2024This systematic review and meta-analysis aimed to assess the magnitude and determinants of diabetic ketoacidosis (DKA) among patients with diabetes mellitus (DM) in... (Meta-Analysis)
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 (I=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.
Topics: Humans; Adolescent; Diabetic Ketoacidosis; Ethiopia; Prevalence; Databases, Factual; Australia; Diabetes Mellitus
PubMed: 38341216
DOI: 10.1136/bmjopen-2023-077151 -
Age and Ageing Jan 2024Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear.
METHODS
We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model.
RESULTS
We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference -0.13, 95%CI: -0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: -0.69 to 0.95), cardiac death (RR 0.80, 95%CI: -0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59-0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis.
CONCLUSIONS
In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.
Topics: Humans; Aged; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Glycated Hemoglobin; Diabetic Ketoacidosis; Sodium-Glucose Transporter 2; Frail Elderly; Heart Failure; Death; Glucose; Sodium
PubMed: 38287703
DOI: 10.1093/ageing/afad254