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Diabetes Care Jun 2023Checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM) is a distinct form of autoimmune diabetes that is a rare complication of immune checkpoint inhibitor... (Review)
Review
BACKGROUND
Checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM) is a distinct form of autoimmune diabetes that is a rare complication of immune checkpoint inhibitor therapy. Data regarding CIADM are limited.
PURPOSE
To systematically review available evidence to identify presentation characteristics and risk factors for early or severe presentations of adult patients with CIADM.
DATA SOURCES
MEDLINE and PubMed databases were reviewed.
STUDY SELECTION
English full text articles from 2014 to April 2022 were identified with a predefined search strategy. Patients meeting diagnostic criteria for CIADM with evidence of hyperglycemia (blood glucose level >11 mmol/L or HbA1c ≥6.5%) and insulin deficiency (C-peptide <0.4 nmol/L and/or diabetic ketoacidosis [DKA]) were included for analysis.
DATA EXTRACTION
With the search strategy we identified 1,206 articles. From 146 articles, 278 patients were labeled with "CIADM," with 192 patients meeting our diagnostic criteria and included in analysis.
DATA SYNTHESIS
Mean ± SD age was 63.4 ± 12.4 years. All but one patient (99.5%) had prior exposure to either anti-PD1 or anti-PD-L1 therapy. Of the 91 patients tested (47.3%), 59.3% had susceptibility haplotypes for type 1 diabetes (T1D). Median time to CIADM onset was 12 weeks (interquartile range 6-24). DKA occurred in 69.7%, and initial C-peptide was low in 91.6%. T1D autoantibodies were present in 40.4% (73 of 179) and were significantly associated with DKA (P = 0.0009) and earlier time to CIADM onset (P = 0.02).
LIMITATIONS
Reporting of follow-up data, lipase, and HLA haplotyping was limited.
CONCLUSIONS
CIADM commonly presents in DKA. While T1D autoantibodies are only positive in 40.4%, they associate with earlier, more severe presentations.
Topics: Adult; Humans; Middle Aged; Aged; Diabetes Mellitus, Type 1; C-Peptide; Risk Factors; Insulin, Regular, Human; Autoantibodies; Diabetic Ketoacidosis
PubMed: 37220262
DOI: 10.2337/dc22-2202 -
Diabetes Research and Clinical Practice Nov 2023Type 1 diabetes mellitus (T1DM) is a chronic childhood disease with potentially persistent CNS disruptions. In this study, we aimed to systematically review diffusion... (Review)
Review
AIMS
Type 1 diabetes mellitus (T1DM) is a chronic childhood disease with potentially persistent CNS disruptions. In this study, we aimed to systematically review diffusion tensor imaging studies in patients with T1DM to understand the microstructural effects of this entity on individuals' brains METHODS: We performed a systematic search and reviewed the studies to include the DTI studies in individuals with T1DM. The data for the relevant studies were extracted and a qualitative synthesis was performed.
RESULTS
A total of 19 studies were included, most of which showed reduced FA widespread in optic radiation, corona radiate, and corpus callosum, as well as other frontal, parietal, and temporal regions in the adult population, while most of the studies in the juvenile patients showed non-significant differences or a non-persistent pattern of changes. Also, reduced AD and MD in individuals with T1DM compared to controls and non-significant differences in RD were noted in the majority of studies. Microstructural alterations were associated with clinical profile, including age, hyperglycemia, diabetic ketoacidosis and cognitive performance.
CONCLUSION
T1DM is associated with microstructural brain alterations including reduced FA, MD, and AD in widespread brain regions, especially in association with glycemic fluctuations and in adult age.
Topics: Adult; Humans; Child; Diffusion Tensor Imaging; Diabetes Mellitus, Type 1; White Matter; Brain
PubMed: 37004976
DOI: 10.1016/j.diabres.2023.110645 -
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 -
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 -
Journal of Anesthesia Jun 2023Although the recommended preoperative cessation period for sodium-glucose cotransporter 2 inhibitors (SGLT2is) changed in 2020 (from 24 h to 3-4 days preoperatively)... (Review)
Review
Although the recommended preoperative cessation period for sodium-glucose cotransporter 2 inhibitors (SGLT2is) changed in 2020 (from 24 h to 3-4 days preoperatively) to reduce the risk of SGLT2i-associated perioperative ketoacidosis (SAPKA), the validity of the new recommendation has not been verified. Using case reports, we assessed the new recommendation effectiveness and extrapolated precipitating factors for SAPKA. We searched electronic databases up to June 1, 2022 to assess SAPKA (blood pH < 7.3 and blood or urine ketone positivity within 30 days postoperatively in patients taking SGLT2i). We included 76 publications with 99 cases. The preoperative SGLT2i cessation duration was reported for 59 patients (59.6%). In all cases with available cessation periods, the SGLT2is were interrupted < 3 days preoperatively. No SAPKA cases with > 2-day preoperative cessation periods were found. Many case reports lack important information for estimating precipitating factors, including preoperative SGLT2i cessation period, body mass index, baseline hemoglobin A1c level, details of perioperative fluid management, and type of anesthesia. Our study suggested that preoperative SGLT2i cessation for at least 3 days could prevent SAPKA. Large prospective epidemiologic studies are needed to identify risk factors for SAPKA.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Sodium-Glucose Transporter 2 Inhibitors; Prospective Studies; Ketosis; Glucose; Sodium
PubMed: 36849747
DOI: 10.1007/s00540-023-03174-8 -
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 Endocrinology 2023Progression to type 1 diabetes (T1D) is defined in stages and clinical disease is preceded by a period of silent autoimmunity. Improved prediction of the risk and rate...
AIM
Progression to type 1 diabetes (T1D) is defined in stages and clinical disease is preceded by a period of silent autoimmunity. Improved prediction of the risk and rate of progression to T1D is needed to reduce the prevalence of diabetic ketoacidosis at presentation as well as for staging participants for clinical trials. This systematic review evaluates novel circulating biomarkers associated with future progression to T1D.
METHODS
PubMed, Ovid, and EBSCO databases were used to identify a comprehensive list of articles. The eligibility criteria included observational studies that evaluated the usefulness of circulating markers in predicting T1D progression in at-risk subjects <20 years old.
RESULTS
Twenty-six studies were identified, seventeen were cohort studies and ten were case control studies. From the 26 studies, 5 found evidence for protein and lipid dysregulation, 11 identified molecular markers while 12 reported on changes in immune parameters during progression to T1D. An increased risk of T1D progression was associated with the presence of altered gene expression, immune markers including regulatory T cell dysfunction and higher short-lived effector CD8 T cells in progressors.
DISCUSSION
Several circulating biomarkers are dysregulated before T1D diagnosis and may be useful in predicting either the risk or rate of progression to T1D. Further studies are required to validate these biomarkers and assess their predictive accuracy before translation into broader use.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier (CRD42020166830).
Topics: Humans; Young Adult; Adult; Diabetes Mellitus, Type 1; CD8-Positive T-Lymphocytes; Disease Progression; Autoimmunity; Biomarkers
PubMed: 36817583
DOI: 10.3389/fendo.2023.1117076 -
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 -
Frontiers in Endocrinology 2022Combined diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) secondary to immune checkpoint inhibitors (ICIs) is extremely rarely reported among ICIs-... (Review)
Review
Combined diabetic ketoacidosis and hyperosmolar hyperglycemic state in type 1 diabetes mellitus induced by immune checkpoint inhibitors: Underrecognized and underreported emergency in ICIs-DM.
BACKGROUND
Combined diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) secondary to immune checkpoint inhibitors (ICIs) is extremely rarely reported among ICIs- diabetes mellitus (DM) cases and is always ignored by physicians. This study aimed to conduct a systematic review to recognize better the rare adverse event of combined DKA-HHS associated with immune checkpoints.
METHODS
A electronic search in Pubmed/Cochrane/Web of Science, complemented by manual searches in article references, was conducted to identify clinical features of ICIs-combined DKA-HHS.
RESULTS
we identified 106 patients with ICIs- type 1 diabetes mellitus (T1DM) from 82 publications: 9 patients presented a coexistence of metabolic acidosis, severe hyperglycemia, and/or DKA; All patients were not diagnosed as combined DKA-HHS. Compared with ICIs-DKA patients, combined DKA-HHS cases were prone to higher hyperglycemia (1020 ± 102.5 vs 686.7 ± 252.6mg/dL). Moreover, acute kidney injury (87.5% vs 28.6%) and prior chemotherapy (66.7% vs 31.6%) showed higher occurrences with the onset of ICIs-HHS or combined DKA-HHS.B.
CONCLUSIONS
Combined DKA-HHS portends a poor diagnosis in patients with coexistence features of DKA and HHS, which healthcare professionals and patients should be aware of due to differences in treatment. Our observational retrospective case series shows that patients with more risk factors were more likely to develop combined DKA-HHS. We are the first to report this group of patients' clinical characteristics and outcomes.
Topics: Humans; Diabetic Ketoacidosis; Hyperglycemic Hyperosmolar Nonketotic Coma; Diabetes Mellitus, Type 1; Immune Checkpoint Inhibitors; Retrospective Studies; Hyperglycemia
PubMed: 36686495
DOI: 10.3389/fendo.2022.1084441 -
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