-
Diabetology & Metabolic Syndrome Oct 2021One possible reason for increased mortality due to SARS-CoV-2 in patients with diabetes is from the complication of diabetic ketoacidosis (DKA).
BACKGROUND
One possible reason for increased mortality due to SARS-CoV-2 in patients with diabetes is from the complication of diabetic ketoacidosis (DKA).
OBJECTIVES
To re-evaluate the association of SARS-CoV-2 and development of DKA and analyse the demographic and biochemical parameters and the clinical outcomes in COVID-19 patients with DKA.
DESIGN
A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed.
METHODS
Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature) were searched from 1 December 2019 to 30 June 2021 in the English language using the following keywords alone or in combination: COVID-19 OR SARS-CoV-2 AND diabetic ketoacidosis OR DKA OR ketosis OR ketonemia OR hyperglycaemic emergency OR hyperglycaemic crisis. We included studies in adults and children of all ages in all healthcare settings. Binary logistic regression model was used to explore the effect of various demographic and biochemical parameters variables on patient's final treatment outcome (survival or death).
RESULTS
Of the 484 papers that were identified, 68 articles were included in the systematic review and meta-analysis (54 case report, 10 case series, and 4 cohort studies). Studies involving 639 DKA patients with confirmed SARS-CoV-2 [46 (7.2%) were children and 334 (52.3%) were adults] were analyzed. The median or mean patient age ranged from < 1 years to 66 years across studies. Most of the patients (n = 309, 48.3%) had pre-existing type 2 diabetes mellitus. The majority of the patients were male (n = 373, 58.4%) and belonged to Hispanic (n = 156, 24.4%) and black (n = 98, 15.3%) ethnicity. The median random blood glucose level, HbA1c, pH, bicarbonate, and anion gap in all included patients at presentation were 507 mg/dl [IQR 399-638 mg/dl], 11.4% [IQR 9.9-13.5%], 7.16 [IQR 7.00-7.22], 10 mmol/l [IQR 6.9-13 mmol/l], and 24.5 mEq/l [18-29.2 mEq/l]; respectively. Mortality rate was [63/243, 25.9%], with a majority of death in patients of Hispanic ethnicity (n = 17, 27%; p = 0.001). The odd ratios of death were significantly high in patients with pre-existing diabetes mellitus type 2 [OR 5.24, 95% CI 2.07-15.19; p = 0.001], old age (≥ 60 years) [OR 3.29, 95% CI 1.38-7.91; p = 0.007], and male gender [OR 2.61, 95% CI 1.37-5.17; p = 0.004] compared to those who survived.
CONCLUSION
DKA is not uncommon in SARS-CoV-2 patients with diabetes mellitus and results in a mortality rate of 25.9%. Mortality key determinants in DKA patients with SARS-CoV-2 infection are individuals with pre-existing diabetes mellitus type 2, older age [≥ 60 years old], male gender, BMI ≥ 30, blood glucose level > 1000 mg/dl, and anion gap ≥ 30 mEq/l.
PubMed: 34702335
DOI: 10.1186/s13098-021-00740-6 -
Clinical Microbiology and Infection :... Jun 2023Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mucormycosis, a rare fungal infection, has shown an increase in the number of reported cases during the COVID-19 pandemic.
OBJECTIVES
To provide a comprehensive insight into the characteristics of COVID-19-associated mucormycosis, through a systematic review and meta-analysis.
METHODS OF DATA SYNTHESIS
Demographic information and clinical features were documented for each patient. Logistic regression analysis was used to predict the risk of mortality.
DATA SOURCES
PubMed, Scopus, Web of Science, Cochrane, CINAHL, Ovid MEDLINE, and FungiSCOPE.
STUDY ELIGIBILITY CRITERIA
Studies reporting individual-level information in patients with adult COVID-19-associated mucormycosis (CAM) between 1 January 2020 and 28 December 2022.
PARTICIPANTS
Adults who developed mucormycosis during or after COVID-19.
INTERVENTIONS
Patients with and without individual clinical variables were compared.
ASSESSMENT OF RISK OF BIAS
Quality assessment was performed based on the National Institutes of Health quality assessment tool for case series studies.
RESULTS
Nine hundred fifty-eight individual cases reported from 45 countries were eligible. 88.1% (844/958) were reported from low- or middle-income countries. Corticosteroid use for COVID-19 (78.5%, 619/789) and diabetes (77.9%, 738/948) were common. Diabetic ketoacidosis (p < 0.001), history of malignancy (p < 0.001), underlying pulmonary (p 0.017), or renal disease (p < 0.001), obesity (p < 0.001), hypertension (p 0.040), age (>65 years) (p 0.001), Aspergillus coinfection (p 0.037), and tocilizumab use during COVID-19 (p 0.018) increased the mortality. CAM occurred on an average of 22 days after COVID-19 and 8 days after hospitalization. Diagnosis of mucormycosis in patients with Aspergillus coinfection and pulmonary mucormycosis was made on average 15.4 days (range, 0-35 days) and 14.0 days (range, 0-53 days) after hospitalization, respectively. Cutaneous mucormycosis accounted for <1% of the cases. The overall mortality rate was 38.9% (303/780).
CONCLUSION
Mortality of CAM was high, and most reports were from low- or middle-income countries. We detected novel risk factors for CAM, such as older age, specific comorbidities, Aspergillus coinfection, and tocilizumab use, in addition to the previously identified factors.
Topics: Adult; Humans; Aged; Mucormycosis; Coinfection; Pandemics; COVID-19; Hospitalization
PubMed: 36921716
DOI: 10.1016/j.cmi.2023.03.008 -
Kidney & Blood Pressure Research 2020The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the...
BACKGROUND
The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the causes and management of aMA from a clinician's perspective.
SUMMARY
We performed a systematic search on PubMed, applying the following search terms: "acute metabolic acidosis," "lactic acidosis," "metformin" AND "acidosis," "unbalanced solutions" AND "acidosis," "bicarbonate" AND "acidosis" AND "outcome," "acute metabolic acidosis" AND "management," and "acute metabolic acidosis" AND "renal replacement therapy (RRT)/dialysis." The literature search did not consider diabetic ketoacidosis at all. Lactic acidosis evolves from various conditions, either with or without systemic hypoxia. The incidence of metformin-associated aMA is actually quite low. Unbalanced electrolyte preparations can induce hyperchloremic aMA. The latter potentially worsens kidney-related outcome parameters. Nevertheless, prospective and controlled data are missing at the moment. Recently, bicarbonate has been shown to improve clinically relevant endpoints in the critically ill, even if higher pH values (>7.3) are targeted. New therapeutics for aMA control are under development, since bicarbonate treatment can induce serious side effects. Key Messages: aMA is a frequent and potentially life-threatening complication of various conditions. Lactic acidosis might occur even in the absence of systemic hypoxia. The incidence of metformin-associated aMA is comparably low. Unbalanced electrolyte solutions induce hyperchloremic aMA, which most likely worsens the renal prognosis of critically ill patients. Bicarbonate, although potentially deleterious due to increased carbon dioxide production with subsequent intracellular acidosis, improves kidney-related endpoints in the critically ill.
Topics: Acidosis; Acidosis, Lactic; Acute Disease; Animals; Bicarbonates; Disease Management; Electrolytes; Humans; Hypoglycemic Agents; Metformin
PubMed: 32663831
DOI: 10.1159/000507813 -
Journal of Clinical & Translational... Dec 2023It has been suggested that there may be an association between type 1 diabetes (T1DM) and suicide, with one study reporting a rate 11 times that of the general... (Review)
Review
BACKGROUND
It has been suggested that there may be an association between type 1 diabetes (T1DM) and suicide, with one study reporting a rate 11 times that of the general population The aim of this paper was to investigate the association between Diabetic ketoacidosis (DKA: a life-threatening acute complication of T1DM) and suicidal behaviours in people with T1DM.
METHODS
We performed a search of the following databases: PubMed, PsychInfo, and Embase for papers which explored the association between suicidal behaviours and self-harm with DKA in T1DM. We excluded case reports and review papers.
RESULTS
Only three papers explored the relationship between DKA and self-harm. One study found an association between DKA and self-harm in a national cohort of people with type 1 diabetes and schizophrenia. The second found a significant increase in psychiatric admissions for self-harm following an episode of DKA. The third study reported that patients with diabetes and a history of self-harm were at elevated risk of a range of diabetes complications including DKA. These findings indicate an association between DKA and self-harm and support the guidelines in recommending a psychosocial assessment where DKA cannot be explained.
CONCLUSIONS
This review suggests that DKA is associated with suicidal or self-injurious behaviours. The small number of studies and the seriousness of this issue highlight the importance of further research on this topic, to improve the evidence base for the identification and treatment of risk of suicidal behaviours in people with T1DM.
PubMed: 37840692
DOI: 10.1016/j.jcte.2023.100325 -
The Cochrane Database of Systematic... Jan 2016Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of uncontrolled diabetes that mainly occurs in individuals with autoimmune type 1 diabetes, but it... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of uncontrolled diabetes that mainly occurs in individuals with autoimmune type 1 diabetes, but it is not uncommon in some people with type 2 diabetes. The treatment of DKA is traditionally accomplished by the administration of intravenous infusion of regular insulin that is initiated in the emergency department and continued in an intensive care unit or a high-dependency unit environment. It is unclear whether people with DKA should be treated with other treatment modalities such as subcutaneous rapid-acting insulin analogues.
OBJECTIVES
To assess the effects of subcutaneous rapid-acting insulin analogues for the treatment of diabetic ketoacidosis.
SEARCH METHODS
We identified eligible trials by searching MEDLINE, PubMed, EMBASE, LILACS, CINAHL, and the Cochrane Library. We searched the trials registers WHO ICTRP Search Portal and ClinicalTrials.gov. The date of last search for all databases was 27 October 2015. We also examined reference lists of included randomised controlled trials (RCTs) and systematic reviews, and contacted trial authors.
SELECTION CRITERIA
We included trials if they were RCTs comparing subcutaneous rapid-acting insulin analogues versus standard intravenous infusion in participants with DKA of any age or sex with type 1 or type 2 diabetes, and in pregnant women.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, assessed studies for risk of bias, and evaluated overall study quality utilising the GRADE instrument. We assessed the statistical heterogeneity of included studies by visually inspecting forest plots and quantifying the diversity using the I² statistic. We synthesised data using random-effects model meta-analysis or descriptive analysis, as appropriate.
MAIN RESULTS
Five trials randomised 201 participants (110 participants to subcutaneous rapid-acting insulin analogues and 91 to intravenous regular insulin). The criteria for DKA were consistent with the American Diabetes Association criteria for mild or moderate DKA. The underlying cause of DKA was mostly poor compliance with diabetes therapy. Most trials did not report on type of diabetes. Younger diabetic participants and children were underrepresented in our included trials (one trial only). Four trials evaluated the effects of the rapid-acting insulin analogue lispro, and one the effects of the rapid-acting insulin analogue aspart. The mean follow-up period as measured by mean hospital stay ranged between two and seven days. Overall, risk of bias of the evaluated trials was unclear in many domains and high for performance bias for the outcome measure time to resolution of DKA.No deaths were reported in the included trials (186 participants; 3 trials; moderate- (insulin lispro) to low-quality evidence (insulin aspart)). There was very low-quality evidence to evaluate the effects of subcutaneous insulin lispro versus intravenous regular insulin on the time to resolution of DKA: mean difference (MD) 0.2 h (95% CI -1.7 to 2.1); P = 0.81; 90 participants; 2 trials. In one trial involving children with DKA, the time to reach a glucose level of 250 mg/dL was similar between insulin lispro and intravenous regular insulin. There was very low-quality evidence to evaluate the effects of subcutaneous insulin aspart versus intravenous regular insulin on the time to resolution of DKA: MD -1 h (95% CI -3.2 to 1.2); P = 0.36; 30 participants; 1 trial. There was low-quality evidence to evaluate the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin on hypoglycaemic episodes: 6 of 80 insulin lispro-treated participants compared with 9 of 76 regular insulin-treated participants reported hypoglycaemic events; risk ratio (RR) 0.59 (95% CI 0.23 to 1.52); P = 0.28; 156 participants; 4 trials. For insulin aspart compared with regular insulin, RR for hypoglycaemic episodes was 1.00 (95% CI 0.07 to 14.55); P = 1.0; 30 participants; 1 trial; low-quality evidence. Socioeconomic effects as measured by length of mean hospital stay for insulin lispro compared with regular insulin showed a MD of -0.4 days (95% CI -1 to 0.2); P = 0.22; 90 participants; 2 trials; low-quality evidence and for insulin aspart compared with regular insulin 1.1 days (95% CI -3.3 to 1.1); P = 0.32; low-quality evidence. Data on morbidity were limited, but no specific events were reported for the comparison of insulin lispro with regular insulin. No trial reported on adverse events other than hypoglycaemic episodes, and no trial investigated patient satisfaction.
AUTHORS' CONCLUSIONS
Our review, which provided mainly data on adults, suggests on the basis of mostly low- to very low-quality evidence that there are neither advantages nor disadvantages when comparing the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin for treating mild or moderate DKA.
Topics: Adult; Child; Diabetic Ketoacidosis; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Short-Acting; Randomized Controlled Trials as Topic; Young Adult
PubMed: 26798030
DOI: 10.1002/14651858.CD011281.pub2 -
Diabetologia Dec 2022Cardiovascular outcome trials (CVOTs) have demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, serious adverse drug reactions have... (Meta-Analysis)
Meta-Analysis Review
AIMS/HYPOTHESIS
Cardiovascular outcome trials (CVOTs) have demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, serious adverse drug reactions have been reported. The risk/benefit ratio of SGLT2i remains unquantified. We aimed to provide an estimation of their risk/benefit ratio in individuals with type 2 diabetes.
METHODS
We conducted a systematic review (MEDLINE, up to 14 September 2021) and meta-analysis. We included randomised CVOTs assessing SGLT2i in individuals with type 2 diabetes with or without other diseases. We used the Cochrane 'Risk of bias' assessment tool. The primary outcomes were overall mortality, major adverse cardiovascular events (MACE), hospitalisation for heart failure (HHF), end-stage renal disease (ESRD), amputation, diabetic ketoacidosis (DKA) and reported genital infections. For each outcome, we estimated the incidence rate ratio (IRR) with a 95% CI; we then computed the number of events expected spontaneously and with SGLT2i.
RESULTS
A total of 46,969 participants from five double-blind, placebo-controlled international trials (weighted mean follow-up 3.5 years) were included. The prevalence of previous CVD ranged from 40.6% to 99.2%. The definition of reported genital infections ranged from 'genital mycotic infection' to 'genital infections that led to discontinuation of the trial regimen or were considered to be serious adverse events'. The number of included studies for each outcomes was five. The use of SGLT2i decreased the risk of all-cause death (IRR 0.86 [95% CI 0.78, 0.95]), MACE (IRR 0.91 [95% CI 0.86, 0.96]), HHF (IRR 0.69 [95% CI 0.62, 0.76]) and ESRD (IRR 0.67 [95% CI 0.53, 0.84]), and increased the risk of DKA (IRR 2.59 [95% CI 1.57, 4.27]) and genital infection (IRR 3.50 [95% CI 3.09, 3.95]) but not of amputation (IRR 1.23 [95% CI 1.00, 1.51]). For 1000 individuals treated over 3.5 years, SGLT2i are expected, on average, to decrease the number of deaths from 70 to 61, to prevent nine MACE, 11 HHF and two cases of ESRD, while inducing two DKA occurrences and 36 genital infections; 778 individuals are expected to avoid all the following outcomes: MACE, HHF, ESRD, amputation, DKA and genital infection.
CONCLUSIONS/INTERPRETATION
Our study is limited to aggregate data. In a population of individuals with type 2 diabetes and a high CVD risk, the cardiovascular and renal benefits of SGLT2i remain substantial despite the risk of DKA and even the hypothetical risk of amputation.
TRIAL REGISTRATION
OSF Registries: https://doi.org/10.17605/OSF.IO/J3R7Y FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Heart Failure; Risk Assessment; Kidney Failure, Chronic; Cardiovascular Diseases; Randomized Controlled Trials as Topic
PubMed: 35925319
DOI: 10.1007/s00125-022-05773-8 -
Diabetes, Obesity & Metabolism Jul 2023To assess the efficacy of bexagliflozin in reducing glycated haemoglobin (HbA1c) and the occurrence of side effects in patients with type 2 diabetes (T2DM). (Meta-Analysis)
Meta-Analysis Review
AIM
To assess the efficacy of bexagliflozin in reducing glycated haemoglobin (HbA1c) and the occurrence of side effects in patients with type 2 diabetes (T2DM).
METHODS
We searched the PubMed, Embase, Cochrane and ClinicalTrials.gov databases for placebo-controlled, randomized clinical trials published up until 15 February 2023. The primary outcome was change in HbA1c. We computed weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs).
RESULTS
A total of six studies and 3111 patients were included, of whom 1951 were prescribed bexagliflozin. Compared with placebo, bexagliflozin significantly reduced HbA1c levels (WMD -0.53%; 95% CI -0.75, -0.31), fasting plasma glucose levels (WMD -1.45 mmol/L; 95% CI -2.32, -0.57), systolic blood pressure (WMD -4.66 mmHg; 95% CI -6.41, -2.92), diastolic blood pressure (WMD -2.12 mmHg; 95% CI -3.94, -0.30), body weight overall (WMD -1.61 kg; 95% CI -2.14, -1.07), and body weight in patients with a body mass index >25 kg/m (WMD -2.05 kg; 95% CI -2.78, -1.31). The proportion of patients who achieved HbA1c < 7% was higher in patients who received bexagliflozin as compared with placebo (OR 1.94; 95% CI 1.36-2.78). There were no significant differences between groups regarding side effects such as hypoglycaemia, genital mycotic infection, urinary tract infection, diarrhoea, headache, nausea, polyuria, diabetic ketoacidosis, or all-cause mortality.
CONCLUSIONS
In this meta-analysis, the use of bexagliflozin was associated with improved clinical and laboratory measures in patients with T2DM compared with placebo, with a similar profile of side effects. These findings support the efficacy of bexagliflozin in the treatment of T2DM.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Glycated Hemoglobin; Sodium-Glucose Transporter 2 Inhibitors; Body Weight; Blood Glucose
PubMed: 36929659
DOI: 10.1111/dom.15051 -
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 -
JAMA Network Open Jun 2023There are reports of increasing incidence of pediatric diabetes since the onset of the COVID-19 pandemic. Given the limitations of individual studies that examine this... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
There are reports of increasing incidence of pediatric diabetes since the onset of the COVID-19 pandemic. Given the limitations of individual studies that examine this association, it is important to synthesize estimates of changes in incidence rates.
OBJECTIVE
To compare the incidence rates of pediatric diabetes during and before the COVID-19 pandemic.
DATA SOURCES
In this systematic review and meta-analysis, electronic databases, including Medline, Embase, the Cochrane database, Scopus, and Web of Science, and the gray literature were searched between January 1, 2020, and March 28, 2023, using subject headings and text word terms related to COVID-19, diabetes, and diabetic ketoacidosis (DKA).
STUDY SELECTION
Studies were independently assessed by 2 reviewers and included if they reported differences in incident diabetes cases during vs before the pandemic in youths younger than 19 years, had a minimum observation period of 12 months during and 12 months before the pandemic, and were published in English.
DATA EXTRACTION AND SYNTHESIS
From records that underwent full-text review, 2 reviewers independently abstracted data and assessed the risk of bias. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Eligible studies were included in the meta-analysis and analyzed with a common and random-effects analysis. Studies not included in the meta-analysis were summarized descriptively.
MAIN OUTCOMES AND MEASURES
The primary outcome was change in the incidence rate of pediatric diabetes during vs before the COVID-19 pandemic. The secondary outcome was change in the incidence rate of DKA among youths with new-onset diabetes during the pandemic.
RESULTS
Forty-two studies including 102 984 incident diabetes cases were included in the systematic review. The meta-analysis of type 1 diabetes incidence rates included 17 studies of 38 149 youths and showed a higher incidence rate during the first year of the pandemic compared with the prepandemic period (incidence rate ratio [IRR], 1.14; 95% CI, 1.08-1.21). There was an increased incidence of diabetes during months 13 to 24 of the pandemic compared with the prepandemic period (IRR, 1.27; 95% CI, 1.18-1.37). Ten studies (23.8%) reported incident type 2 diabetes cases in both periods. These studies did not report incidence rates, so results were not pooled. Fifteen studies (35.7%) reported DKA incidence and found a higher rate during the pandemic compared with before the pandemic (IRR, 1.26; 95% CI, 1.17-1.36).
CONCLUSIONS AND RELEVANCE
This study found that incidence rates of type 1 diabetes and DKA at diabetes onset in children and adolescents were higher after the start of the COVID-19 pandemic than before the pandemic. Increased resources and support may be needed for the growing number of children and adolescents with diabetes. Future studies are needed to assess whether this trend persists and may help elucidate possible underlying mechanisms to explain temporal changes.
Topics: Child; Humans; Incidence; Diabetes Mellitus, Type 1; Pandemics; Diabetes Mellitus, Type 2; COVID-19; Diabetic Ketoacidosis
PubMed: 37389869
DOI: 10.1001/jamanetworkopen.2023.21281 -
Psychopharmacology Oct 2016Patients exposed to second-generation antipsychotics (SGAs) have approximately 10 times increased risk of diabetic ketoacidosis (DKA) compared with the general... (Review)
Review
RATIONALE
Patients exposed to second-generation antipsychotics (SGAs) have approximately 10 times increased risk of diabetic ketoacidosis (DKA) compared with the general population. However, as DKA is a rare complication of type 2 diabetes mellitus, and susceptible patients exposed to antipsychotics may rapidly develop DKA independently of treatment duration and weight gain, this is rather suggestive of type 1 diabetes mellitus (T1DM) or latent autoimmune diabetes in adults.
OBJECTIVES
We performed a systematic review of current studies regarding antipsychotic-associated DKA with type 1 etiology and analyzed Danish adverse drug event (ADE) reports (previously unpublished cases).
METHODS
PubMed, Embase, and the Cochrane Library were searched for all relevant studies, and the Danish Medicines Agency retrieved ADE reports using the Danish ADE database (up to date as of June 28, 2016). Diagnosis of antipsychotic-associated DKA with type 1 etiology was either considered confirmed or possible depending on authors' conclusions in the studies and/or clinical aspects. In addition, clinico-demographic risk factors were extracted.
RESULTS
A total of 655 records and 11 ADE reports were identified, and after screening for eligibility, we included 21 case reports/series and two ADE reports (n = 24). No relevant clinical studies were included. Although fatal cases were identified, these were excluded because of diagnostic uncertainties (n = 15). DKA occurred in 15 males (62.5 %) and nine females (37.5 %), with a mean age ± standard deviation of 34.8 ± 12.4 years. Median time to DKA was 5 months (interquartile range: 1.4-11 months). Associated antipsychotics were olanzapine (n = 9, 36 %), aripiprazole (n = 6, 24 %), risperidone (n = 6, 24 %), clozapine (n = 3, 12 %), and quetiapine (n = 1, 4 %). Nine patients (37.5 %) were confirmedly diagnosed with T1DM following DKA resolution, whereas 15 patients (62.5 %) had possible T1DM. In 22 patients (91.7 %), ongoing insulin treatment was required for glycemic control.
CONCLUSIONS
Increased awareness of the potential risk of antipsychotic-associated DKA and subsequent T1DM diagnosis, with insulin requirements for glycemic control, is warranted. The underlying mechanisms are poorly understood but most probably multifactorial. Certainly, further studies are warranted. Clinicians must utilize appropriate monitoring in susceptible patients and consider the possibility of continuing antipsychotic treatment with appropriate diabetic care.
Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Clozapine; Denmark; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Olanzapine; Risk Factors; Risperidone; Young Adult
PubMed: 27592232
DOI: 10.1007/s00213-016-4411-x