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Journal of Oncology Pharmacy Practice :... May 2024Immunotherapy has a crucial role in the current treatment of multiple malignancies. Albeit described as rare, new onset autoimmune diabetes is a potentially...
INTRODUCTION
Immunotherapy has a crucial role in the current treatment of multiple malignancies. Albeit described as rare, new onset autoimmune diabetes is a potentially life-threatening complication of programmed cell death-1 (PD-1) inhibitors, such as pembrolizumab, and its predisposing factors and pathological mechanism are yet to be clarified.
CASE REPORT
We present a case of a 72-year-old man with a high-grade bladder carcinoma undergoing pembrolizumab treatment. He had no personal or family history of diabetes mellitus but was diagnosed with primary hypothyroidism four months after starting pembrolizumab. Two years after starting pembrolizumab, he presented in the emergency department due to abdominal pain, anorexia, polydipsia, polyuria and vomiting over the preceding five days and he met criteria for severe diabetic ketoacidosis (DKA). Three days prior to his admission, he had received prednisolone therapy for suspected hypersensitivity related to a contrast-enhanced imaging that he performed.
MANAGEMENT & OUTCOME
Prompt treatment for DKA was started, with transition to insulin basal-bolus therapy after DKA resolution, with progressive glycaemic stabilization. Further investigation revealed low C-peptide levels (0.07 ng/dL, with a fasting blood glucose of 288 mg/dL), HbA1c 9.2% and positive anti-IA2 antibodies, which allowed the diagnosis of new-onset autoimmune diabetes. Pembrolizumab was transiently suspended, and the patient resumed treatment after glycaemic profile optimization under multiple daily insulin administrations two months later.
DISCUSSION
This case highlights the importance of clinical suspicion and glycaemic monitoring as an integral part of treatment protocols in patients on pembrolizumab and other immune checkpoint inhibitors. Additional research and investigation into the underlying mechanisms of this condition are necessary to identify potential screening tests for individuals at higher risk of developing DM and to guide the implementation of management and preventive strategies for ketoacidosis complication.
PubMed: 38766907
DOI: 10.1177/10781552241255699 -
Diabetes, Metabolic Syndrome and... 2023This study aimed to characterize adult patients admitted with diabetic ketoacidosis (DKA) in northern Jordan.
PURPOSE
This study aimed to characterize adult patients admitted with diabetic ketoacidosis (DKA) in northern Jordan.
METHODS
The study examined medical records of patients diagnosed with DKA from January 2015 to April 2018. Variables analyzed included diabetes type, precipitating illness, admission month, hospital length of stay, and biochemical markers.
RESULTS
Out of 232 admissions with DKA, 70% were diagnosed with type 2 diabetes, and 56% were females. 12% of admissions had a new diagnosis of diabetes, of which 51% had type 2 diabetes. Sepsis (48%), Non-adherence (26%), and diabetic foot infections (18%) were the most encountered precipitating factors for DKA in T1DM. As for T2DM, sepsis (52%), acute coronary syndrome (12%), and pancreatitis (8%) were the most precipitating factors for DKA. High urea levels, high creatinine levels, low phosphorous levels, low hemoglobin levels, and high platelet counts were associated with a longer hospital stay for type 1 diabetes. For type 2 diabetes, low pH on admission, old age, and high Hb A1c within 6 months of admission were factors associated with a prolonged hospital stay. The study found a significant peak of admissions for DKA in both type 1 and type 2 patients in the winter and spring months (Pearson P-value= 0.0013).
CONCLUSION
The results of the present study highlight the seasonal variation in the frequency of DKA hospitalizations. It also highlights sepsis as the most frequent precipitating factor of DKA in both type 1 and type 2 DM patients.
PubMed: 37810572
DOI: 10.2147/DMSO.S413405 -
American Journal of Perinatology Jun 2024The study's primary objective was to evaluate adverse outcomes among reproductive-age hospitalizations with diabetic ketoacidosis (DKA), comparing those that are...
OBJECTIVE
The study's primary objective was to evaluate adverse outcomes among reproductive-age hospitalizations with diabetic ketoacidosis (DKA), comparing those that are pregnancy-related versus nonpregnancy-related and evaluating temporal trends.
STUDY DESIGN
We conducted a retrospective cross-sectional study using the National Inpatient Sample to identify hospitalizations with DKA among reproductive-age women (15-49 years) in the United States (2016-2020). DKA in pregnancy hospitalizations was compared with DKA in nonpregnant hospitalizations. Adverse outcomes evaluated included mechanical ventilation, coma, seizures, renal failure, prolonged hospital stay, and in-hospital death. Multivariable Poisson regression models with robust error variance were used to estimate adjusted relative risk (aRR) and 95% confidence interval (CI). Annual percent change (APC) was used to calculate the change in DKA rate over time.
RESULTS
Among 35,210,711 hospitalizations of reproductive-age women, 447,600 (1.2%) were hospitalized with DKA, and among them, 13,390 (3%) hospitalizations were pregnancy-related. The rate of nonpregnancy-related DKA hospitalizations increased over time (APC = 3.8%, 95% CI = 1.5-6.1). After multivariable adjustment, compared with pregnancy-related hospitalizations with DKA, the rates of mechanical ventilation (aRR = 1.56, 95% CI = 1.18-2.06), seizures (aRR = 2.26, 95% CI = 1.72-2.97), renal failure (aRR = 2.26, 95% CI = 2.05-2.50), coma (aRR = 2.53, 95% CI = 1.68-3.83), and in-hospital death (aRR = 2.38, 95% CI = 1.06-5.36) were higher among nonpregnancy-related hospitalizations with DKA.
CONCLUSION
A nationally representative sample of hospitalizations indicates that over the 5-year period, the rate of nonpregnancy-related DKA hospitalizations increased among reproductive age women, and a higher risk of adverse outcomes was observed when compared with pregnancy-related DKA hospitalizations.
KEY POINTS
· Over 5 years, the rate of pregnancy-related DKA hospitalizations was stable.. · Over 5 years, the rate of nonpregnancy-related DKA hospitalizations increased.. · There is a higher risk of adverse outcomes with DKA outside of pregnancy..
PubMed: 38806155
DOI: 10.1055/a-2334-8692 -
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 -
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 -
Forensic Science, Medicine, and... Mar 2024Acute necrotizing esophagitis (ANE), acute necrotising duodenitis (AND), and Wishnesky's lesions (WLs) are three peculiar upper gastrointestinal pathologies that can be...
Acute necrotizing esophagitis (ANE), acute necrotising duodenitis (AND), and Wishnesky's lesions (WLs) are three peculiar upper gastrointestinal pathologies that can be seen in death from diabetic ketoacidosis (DKA). Amongst these three, AND has only been recently described. Morphologically, ANE and AND present as generalized black discoloration of the intestinal tract, and florid necrosis and inflammation. Whereas WLs are discrete black lesions in the stomach with necrosis and muted inflammation. We report a case of isolated AND with an unusual morphology not previously reported. A man in his 60s was found dead at home who died from pneumonia complicated by DKA. The gastrointestinal tract showed isolated patchy and discrete AND in which macroscopically resembled WLs, but microscopy resembled ANE with florid necrosis and acute inflammation. This case, together with the literature, documented AND can be macroscopically diffuse or discrete resembling ANE or WLs respectively but microscopically resemble ANE. Furthermore, the potential of these lesions being found in isolation in DKA raises the possibility of both general and local mechanisms playing a role on their morphology and presentation.
PubMed: 38446333
DOI: 10.1007/s12024-024-00800-z -
Medicina 2024Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that are increasingly used in cancer treatments. As experience in the use of immunotherapy increases, more... (Review)
Review
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that are increasingly used in cancer treatments. As experience in the use of immunotherapy increases, more is known about its safety profile and immune-mediated adverse effects. Among them is diabetic ketoacidosis (DKA), a rare but serious fatal complication of treatment. In this paper we describe the cases of three patients who presented with episodes of DKA during treatment with ICIs, two of which manifested with fulminant forms, leading to an acute course with initially normal glycosylated hemoglobin values. In addition, we conducted a review of the literature on DKA associated with ICIs in order to highlight the importance of noticing these potentially fatal complications and promptly establishing appropriate therapy.
Topics: Humans; Diabetic Ketoacidosis; Antibodies, Monoclonal; Immunotherapy; Drug-Related Side Effects and Adverse Reactions; Diabetes Mellitus
PubMed: 38271940
DOI: No ID Found -
Proceedings (Baylor University. Medical... 2024
PubMed: 38628337
DOI: 10.1080/08998280.2024.2324652 -
Annals of Medicine Dec 2023The increasing prevalence of diabetic ketoacidosis (DKA) related admissions poses a significant burden on the healthcare systems globally. However, data regarding the...
BACKGROUND
The increasing prevalence of diabetic ketoacidosis (DKA) related admissions poses a significant burden on the healthcare systems globally. However, data regarding the predictors of healthcare resource utilization in DKA is limited and inconsistent. This study aimed to identify key predictors of hospital length of stay (LOS), readmission and recurrent DKA episodes.
METHODS
We undertook a retrospective cross-sectional analysis of all DKA admissions from 2015 to 2021 across four hospitals in Qatar. The primary outcomes were the length of stay (LOS), 90-day readmission and 6-month and 1-year DKA recurrence.
RESULTS
We included 922 patients with a median age of 35 years (25-45). 62% were males with type-1 diabetes-mellitus (T1DM) and type-2 DM (T2DM), present in 52% and 48% of patients. The median LOS was 2.6 days (IQR 1.1-4.8), and the median DKA resolution time was 18 h (10.5-29). Male-gender, new-onset DM, higher Charlson Comorbidity Index (CCI), lower haemoglobin, sodium and potassium, higher urea, longer DKA duration and MICU admission predicted a longer LOS in a multivariate regression analysis. None of the factors were significantly associated with 90-day readmission. Patients with pre-existing T1DM were more likely to have a six-month DKA recurrence than pre-existing T2DM. Patients with a 6-month DKA recurrence, female gender and T1DM had higher odds of 12-month recurrence, whereas a consult with a diabetes educator at the index admission was associated with decreased odds of recurrence.
CONCLUSIONS/INTERPRETATION
This is the most extensive study from the Middle-East region reporting on LOS, readmissions and the recurrence of DKA. Results from this study with a diverse population may be valuable for physicians and healthcare systems to decrease the diabetes-related healthcare burden in DKA patients.
Topics: Humans; Male; Female; Adult; Middle Aged; Length of Stay; Diabetic Ketoacidosis; Patient Readmission; Diabetes Mellitus, Type 1; Retrospective Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2
PubMed: 36745515
DOI: 10.1080/07853890.2023.2175031