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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 -
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 -
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 -
European Journal of Endocrinology Sep 2019To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs).
OBJECTIVE
To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs).
DESIGN AND METHODS
We report the case of a lung cancer patient with diabetic ketoacidosis (DKA) and autoimmune thyroiditis during pembrolizumab treatment. We provide a systematic review of all published cases (PubMed/Web of Science/Cochrane, through November 2018) of autoimmune diabetes mellitus related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-, programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy.
RESULTS
Our literature search identified 90 patient cases (our case excluded). Most patients were treated with anti-PD-1 or anti-PD-L1 as monotherapy (79%) or in combination with CTLA-4 blockade (15%). On average, diabetes mellitus was diagnosed after 4.5 cycles; earlier for combination ICI at 2.7 cycles. Early-onset diabetes mellitus (after one or two cycles) was observed during all treatment regimens. Diabetic ketoacidosis was present in 71%, while elevated lipase levels were detected in 52% (13/25). Islet autoantibodies were positive in 53% of patients with a predominance of glutamic acid decarboxylase antibodies. Susceptible HLA genotypes were present in 65% (mostly DR4). Thyroid dysfunction was the most frequent other endocrine AE at 24% incidence in this patient population.
CONCLUSION
ICI-related diabetes mellitus is a rare but often life-threatening metabolic urgency of which health-care professionals and patients should be aware. Close monitoring of blood glucose and prompt endocrine investigation in case of hyperglycemia is advisable. Predisposing factors such as HLA genotype might explain why some individuals are at risk.
Topics: Antineoplastic Agents, Immunological; Carcinoma, Non-Small-Cell Lung; Diabetes Mellitus, Type 1; Humans; Immunologic Factors; Lung Neoplasms; Male; Middle Aged
PubMed: 31330498
DOI: 10.1530/EJE-19-0291 -
Diabetologia Apr 2022The aim of this work was to assess the effectiveness of continuous glucose monitoring (CGM) vs self-monitoring of blood glucose (SMBG) in maintaining glycaemic control... (Meta-Analysis)
Meta-Analysis Review
Effectiveness of continuous glucose monitoring in maintaining glycaemic control among people with type 1 diabetes mellitus: a systematic review of randomised controlled trials and meta-analysis.
AIMS/HYPOTHESIS
The aim of this work was to assess the effectiveness of continuous glucose monitoring (CGM) vs self-monitoring of blood glucose (SMBG) in maintaining glycaemic control among people with type 1 diabetes mellitus.
METHODS
Cochrane Library, PubMed, Embase, CINAHL, Scopus, trial registries and grey literature were searched from 9 June 2011 until 22 December 2020 for RCTs comparing CGM intervention against SMBG control among the non-pregnant individuals with type 1 diabetes mellitus of all ages and both sexes on multiple daily injections or continuous subcutaneous insulin infusion with HbA levels, severe hypoglycaemia and diabetic ketoacidosis (DKA) as outcomes. Studies also included any individual or caregiver-led CGM systems. Studies involving GlucoWatch were excluded. Risk of bias was appraised with Cochrane risk of bias tool. Meta-analysis and meta-regression were performed using Review Manager software and R software, respectively. Heterogeneity was evaluated using χ and I statistics. Overall effects and certainty of evidence were evaluated using Z statistic and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) software.
RESULTS
Twenty-two studies, involving 2188 individuals with type 1 diabetes, were identified. Most studies had low risk of bias. Meta-analysis of 21 studies involving 2149 individuals revealed that CGM significantly decreased HbA levels compared with SMBG (mean difference -2.46 mmol/mol [-0.23%] [95% CI -3.83, -1.08], Z = 3.50, p=0.0005), with larger effects experienced among higher baseline HbA >64 mmol/mol (>8%) individuals (mean difference -4.67 mmol/mol [-0.43%] [95% CI -6.04, -3.30], Z = 6.69, p<0.00001). However, CGM had no influence on the number of severe hypoglycaemia (p=0.13) and DKA events (p=0.88). Certainty of evidence was moderate.
CONCLUSIONS/INTERPRETATION
CGM is superior to SMBG in improving glycaemic control among individuals with type 1 diabetes in the community, especially in those with uncontrolled glycaemia. Individuals with type 1 diabetes with HbA >64 mmol/mol (>8%) are most likely to benefit from CGM. Current findings could not confer a concrete conclusion on the effectiveness of CGM on DKA outcome as DKA incidences were rare. Current evidence is also limited to outpatient settings. Future research should evaluate the accuracy of CGM and the effectiveness of CGM across different age groups and insulin regimens as these remain unclear in this paper.
PROSPERO REGISTRATION
Registration no. CRD42020207042.
FUNDING
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Glycemic Control; Humans; Hypoglycemia; Insulin; Male
PubMed: 35141761
DOI: 10.1007/s00125-021-05648-4 -
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 -
Cardiovascular Diabetology Mar 2022We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients with diabetic kidney disease (DKD).
METHODS
We searched electronic databases for major randomized placebo-controlled clinical trials published up to September 30, 2021 and reporting on cardiovascular and kidney outcomes of SGLT2i in patients with DKD. DKD was defined as chronic kidney disease in individuals with type 2 diabetes. Random-effects meta-analysis models were used to estimate pooled hazard ratios (HR) and 95% confidence intervals (CI) for clinical outcomes including major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, and cardiovascular death), kidney composite outcomes (a combination of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes), hospitalizations for heart failure (HHF), deaths and safety events (mycotic infections, diabetic ketoacidosis [DKA], volume depletion, amputations, fractures, urinary tract infections [UTI], acute kidney injury [AKI], and hyperkalemia).
RESULTS
A total of 26,106 participants with DKD from 8 large-scale trials were included (median age: 65.2 years, 29.7-41.8% women, 53.2-93.2% White, median follow-up: 2.5 years). SGLT2i were associated with reduced risks of MACE (HR 0.83, 95% CI 0.75-0.93), kidney composite outcomes (HR 0.66, 95% CI 0.58-0.75), HHF (HR 0.62, 95% CI 0.55-0.71), cardiovascular death (HR 0.84, 95% CI 0.74-0.96), MI (HR 0.78, 95% CI 0.67-0.92), stroke (HR 0.76, 95% CI 0.59-0.97), and all-cause death (HR 0.86, 95% CI 0.77-0.96), with no significant heterogeneity detected. Similar results were observed among participants with reduced estimated glomerular filtration rate (eGFR: < 60 mL/min/1.73m). The relative risks (95% CI) for adverse events were 3.89 (1.42-10.62) and 2.50 (1.32-4.72) for mycotic infections in men and women respectively, 3.54 (0.82-15.39) for DKA, and 1.29 (1.13-1.48) for volume depletion.
CONCLUSIONS
Among adults with DKD, SGLT2i were associated with reduced risks of MACE, kidney outcomes, HHF, and death. With a few exceptions of more clear safety signals, we found overall limited data on the associations between SGLT2i and safety outcomes. More research is needed on the safety profile of SGLT2i in this population.
Topics: Adult; Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diabetic Nephropathies; Female; Heart Failure; Humans; Kidney; Male; Myocardial Infarction; Sodium-Glucose Transporter 2 Inhibitors; Stroke
PubMed: 35321742
DOI: 10.1186/s12933-022-01476-x -
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 -
BMJ Open Feb 2019To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies.
DESIGN
We conducted a systematic review and meta-analysis of randomised controlled trials (RCT). Six large databases were searched from inception to May 2018. Random effects models were used to estimate pooled relative risks (RRs).
INTERVENTION
SGLT2 inhibitors, compared with placebo or active comparators.
PRIMARY OUTCOMES
Acute kidney injury (AKI), diabetic ketoacidosis (DKA), urinary tract infections (UTI), bone fractures and lower limb amputations.
RESULTS
We screened 2418 citations of which 109 were included. Most studies included one of four SGLT2 inhibitors, dapagliflozin, canagliflozin, empagliflozin and ipragliflozin. When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I=0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I=0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I=0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I=1.3%). Three studies reported on amputation, with one finding a significant increase risk. No increased risk for either outcome was found when compared with active controls. Subgroup analysis did show an increased risk of UTI with dapagliflozin only (RR 1.21; 95% CI 1.02 to 1.43, I=0.0%), but no other analysis supported an increased risk of AKI, DKA, UTI or fracture.
CONCLUSIONS
Current evidence from RCTs does not suggest an increased risk of harm with SGLT2 inhibitors as a class over placebo or active comparators with respect to AKI, DKA, UTI or fracture. However, wide CIs for many comparisons suggest limited precision, and therefore clinically important adverse events cannot be ruled out. Dapagliflozin, appears to independently increase the risk of UTI, although the mechanism for this intraclass variation in risk is unclear.
PROSPERO REGISTRATION NUMBER
CRD42016038715.
Topics: Acute Kidney Injury; Amputation, Surgical; Benzhydryl Compounds; Canagliflozin; Diabetic Ketoacidosis; Fractures, Bone; Glucosides; Humans; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes; Urinary Tract Infections
PubMed: 30813108
DOI: 10.1136/bmjopen-2018-022577 -
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