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The Journal of International Medical... Nov 2023To provide an overview of reported cases of new-onset type 1 diabetes mellitus (T1D) following COVID-19 infection.
AIMS
To provide an overview of reported cases of new-onset type 1 diabetes mellitus (T1D) following COVID-19 infection.
METHODS
PubMed and Scopus library databases were screened for relevant case reports published between January 2020 and June 2022. Study design, geographic region or language were not restricted.
RESULTS
Twenty studies were identified and involved 37 patients (20 [54%] male, 17 [46%] female). Median age was 11.5 years (range 8 months-33 years) and 31 (84%) patients were aged ≤17 years. Most patients (33, 89%) presented with diabetic ketoacidosis (DKA). In total, 23 (62%) patients presented at the time of positive COVID-19 testing and 14 (38%) had symptoms consistent with COVID-19 infection or a previous positive test (1-56 days). Diabetes symptomatology was provided in 22 cases and (19, 86%) reported polyuria, polydipsia, polyphagia, fatigue, or weight loss or a combination of the aforementioned in the preceding weeks (3 days-12 weeks). Of the 28 patients that had data on acute and long-term treatment, all recovered well and most were managed with basal bolus insulin regimens. Quality assessment showed that most reports were either 'good' or 'moderate quality'.
CONCLUSIONS
Although uncommon, new-onset T1D is a condition healthcare professionals may expect to see following a COVID-19 infection.
Topics: Female; Humans; Infant; Male; COVID-19; COVID-19 Testing; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Polyuria; Case Reports as Topic
PubMed: 37940619
DOI: 10.1177/03000605231210403 -
Heart Failure Reviews Jan 2024Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection... (Meta-Analysis)
Meta-Analysis Review
Sodium-glucose cotransoporter-2 inhibitors (SGLT-2Is) improve prognosis in heart failure (HF) patients both with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). However, these drugs can have some side effects. To estimate the relative risk of side effects in HF patients treated with SGLT-2Is irrespective from left ventricular EF and setting (chronic and non-chronic HF). Five randomized controlled trials (RCTs) enrolling patients with HFrEF, 4 RCTs enrolling non-chronic HF, and 3 RCTs enrolling HFpEF were included. Among side effects, urinary infection, genital infection, acute kidney injury, diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations were considered in the analysis. Overall, 24,055 patients were included in the analysis: 9020 (38%) patients with HFrEF, 12,562 (52%) with HFpEF, and 2473 (10%) with non-chronic HF. There were no differences between SGLT-2Is and placebo in the risk to develop diabetic ketoacidosis, hypoglycemia, hyperkalemia, hypokalemia, bone fractures, and amputations. HFrEF patients treated with SGLT-2Is had a significant reduction of acute kidney injury (RR = 0.54 (95% CI 0.33-0.87), p = 0.011), whereas no differences have been reported in the HFpEF group (RR = 0.94 (95% CI 0.83-1.07), p = 0.348) and non-chronic HF setting (RR = 0.79 (95% CI 0.55-1.15), p = 0.214). A higher risk to develop genital infection (overall 2.57 (95% CI 1.82-3.63), p < 0.001) was found among patients treated with SGLT-2Is irrespective from EF (HFrEF: RR = 1.96 (95% CI 1.17-3.29), p = 0.011; HFpEF: RR = 3.04 (95% CI 1.88-4.90), p < 0.001). The risk to develop urinary infections was increased among SGLT-2I users in the overall population (RR = 1.13 (95% CI 1.00-1.28), p = 0.046) and in the HFpEF setting (RR = 1.19 (95% CI 1.02-1.38), p = 0.029), whereas no differences have been reported in HFrEF (RR = 1.05 (95% CI 0.81-1.36), p = 0.725) and in non-chronic HF setting (RR = 1.04 (95% CI 0.75-1.46), p = 0.806). SGLT-2Is increase the risk of urinary and genital infections in HF patients. In HFpEF patients, the treatment increases the risk of urinary infections compared to placebo, whereas SGLT-2Is reduce the risk of acute kidney disease in patients with HFrEF.
Topics: Humans; Stroke Volume; Diabetic Ketoacidosis; Hyperkalemia; Hypokalemia; Heart Failure; Hypoglycemia; Acute Kidney Injury; Fractures, Bone; Glucose
PubMed: 37917192
DOI: 10.1007/s10741-023-10363-w -
Journal of Diabetes and Its... Dec 2023Patients undergoing insulin-based therapy for type 1 diabetes often experience poor glycemic control characterized by significant fluctuations. This study was undertaken... (Meta-Analysis)
Meta-Analysis
The effect of sodium-glucose cotransporter 2 inhibitors as an adjunct to insulin in patients with type 1 diabetes assessed by continuous glucose monitoring: A systematic review and meta-analysis.
AIMS
Patients undergoing insulin-based therapy for type 1 diabetes often experience poor glycemic control characterized by significant fluctuations. This study was undertaken to analyze the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2Is), as an adjunct to insulin, on time in range (TIR) and glycemic variability in patients with type 1 diabetes, using continuous glucose monitoring (CGM). In addition, we examined which type of SGLT2I yielded a superior effect compared to others.
METHODS
We conducted a comprehensive search of PubMed, EMBASE, the Cochrane Library, Web of Science, and clinical trial registry websites, retrieving all eligible randomized clinical trials (RCTs) published up until February 2023. We analyzed the mean TIR, mean amplitude of glucose excursions (MAGE), mean daily glucose (MDG), diabetic ketoacidosis (DKA), standard deviation (SD), total insulin dose, and severe hypoglycemia to evaluate the efficacy and safety of SGLT2Is. A random-effects model was also employed.
RESULTS
This study encompassed 15 RCTs. The meta-analysis revealed that the use of SGLT2Is as an adjuvant therapy to insulin led to a significant increase in TIR (MD = 10.78, 95%CI = 9.33-12.23, I = 42 %, P < 0.00001) and a decrease in SD (MD = -0.38, 95%CI = -0.50 to -0.26, I = 0 %, P < 0.00001), MAGE (MD = -0.92, 95%CI = -1.17 to -0.67, I = 19 %, P < 0.00001), MDG(MD = -1.01, 95%CI = -1.32 to -0.70, I = 48 %, P < 0.00001), and total insulin dose (MD = -5.81, 95%CI = -7.81 to -3.82, I = 32 %, P < 0.00001). No significant increase was observed in the rate of severe hypoglycemia (RR = 1.04, 95 % CI = 0.76-1.43, P = 0.80). However, SGLT2I therapy was associated with increased DKA occurrence (RR = 2.79, 95 % CI = 1.42-5.48; P = 0.003, I = 16 %). In addition, the subgroup analyses based on the type of SGLT2Is revealed that dapagliflozin might exhibit greater efficacy compared to other SGLT2Is across most outcomes.
CONCLUSIONS
SGLT2Is exhibited a positive effect on improving blood glucose level fluctuations. Subgroup analysis showed that dapagliflozin appeared to have more advantages. However, giving due consideration to preventing adverse effects, particularly DKA, is paramount.
REGISTRATION
Prospero CRD42023408276.
Topics: Humans; Diabetes Mellitus, Type 1; Insulin; Hypoglycemic Agents; Sodium-Glucose Transporter 2 Inhibitors; Insulin, Regular, Human; Diabetic Ketoacidosis; Hypoglycemia; Glucose; Sodium; Randomized Controlled Trials as Topic
PubMed: 37907042
DOI: 10.1016/j.jdiacomp.2023.108632 -
Frontiers in Pharmacology 2023This study aimed to investigate the association between the use of sodium-glucose transporter 2 inhibitors (SGLT-2i) and the risk of diabetic ketoacidosis (DKA), lower...
This study aimed to investigate the association between the use of sodium-glucose transporter 2 inhibitors (SGLT-2i) and the risk of diabetic ketoacidosis (DKA), lower limb amputation (LLA), urinary tract infections (UTI), genital tract infections (GTI), bone fracture, and hypoglycemia in cohort studies. A systematic search was conducted in the PubMed and Embase databases to identify cohort studies comparing the safety of SGLT-2i versus other glucose-lowering drugs (oGLD) in patients with type 2 diabetes mellitus (T2DM). The quality of the studies was assessed using the Newcastle-Ottawa Scale. Primary endpoints were DKA and LLA, while secondary endpoints included UTI, GTI, bone fracture, and hypoglycemia. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated. A total of 9,911,454 patients from 40 cohort studies were included in the analysis. SGLT-2i use was associated with a higher risk of DKA (HR: 1.21, 95% CI: 1.07-1.38, = 0.003) and GTI (HR: 2.72, 95% CI: 2.48-2.98, < 0.01). However, it was not associated with an increased risk of LLA (HR: 1.06, 95% CI: 0.92-1.23, = 0.42), UTI (HR: 0.99, 95% CI: 0.89-1.10, = 0.83), or bone fracture (HR: 0.99, 95% CI: 0.94-1.04, = 0.66). Furthermore, SGLT-2i was associated with a reduced risk of hypoglycemia. Furthermore, compared to dipeptidyl peptidase 4 inhibitors, SGLT-2i as a class and individually was associated with an increased risk of DKA. Canagliflozin specifically increased the risk of LLA (HR: 1.19, 95% CI: 1.04-1.36, = 0.01). The subgroup analysis suggested that SGLT-2i increased the risk of LLA among patients with a history of cardiovascular disease. SGLT-2i versus oGLD was associated with a similar occurrence of LLA, UTI, and bone fracture. However, SGLT-2i was associated with a higher risk of DKA and GTI than oGLD. These findings provide valuable information on the safety profile of SGLT-2i in patients with T2DM and can help inform clinical decision-making.
PubMed: 37905204
DOI: 10.3389/fphar.2023.1275060 -
Diabetes/metabolism Research and Reviews Mar 2024Ketosis-prone type 2 diabetes was defined by the World Health Organization in 2019. According to the literature, the diagnosis is based on the presence of ketosis, islet... (Meta-Analysis)
Meta-Analysis
AIMS
Ketosis-prone type 2 diabetes was defined by the World Health Organization in 2019. According to the literature, the diagnosis is based on the presence of ketosis, islet autoantibody negativity and preserved insulin secretion. Our meta-analysis assessed the prevalence and clinical characteristics of ketosis-prone type 2 diabetes among patients hospitalised with diabetic ketoacidosis (DKA) or ketosis.
METHODS
The systematic search was performed in five main databases as of 15 October 2021 without restrictions. We calculated the pooled prevalence of ketosis-prone type 2 diabetes (exposed group) within the diabetic population under examination, patients with ketoacidosis or ketosis, to identify the clinical characteristics, and we compared it to type 1 diabetes (the comparator group). The random effects model provided pooled estimates as prevalence, odds ratio and mean difference (MD) with 95% confidence intervals.
RESULTS
Eleven articles were eligible for meta-analysis, thus incorporating 2010 patients of various ethnic backgrounds. Among patients presenting with DKA or ketosis at the onset of diabetes, 35% (95% CI: 24%-49%) had ketosis-prone type 2 diabetes. These patients were older (MD = 11.55 years; 95% CI: 5.5-17.6) and had a significantly higher body mass index (BMI) (MD = 5.48 kg/m ; 95% CI: 3.25-7.72) than those with type 1 diabetes.
CONCLUSIONS
Ketosis-prone type 2 diabetes accounts for one third of DKA or ketosis at the onset of diabetes in adults. These patients are characterised by islet autoantibody negativity and preserved insulin secretion. They are older and have a higher BMI compared with type 1 diabetes. C-peptide and diabetes-related autoantibody measurement is essential to identify this subgroup among patients with ketosis at the onset of diabetes.
Topics: Adult; Humans; Diabetic Ketoacidosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Ketosis; Autoantibodies
PubMed: 37888894
DOI: 10.1002/dmrr.3743 -
Journal of the American Pharmacists... 2024The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The U.S. Food and Drug Administration (FDA) revised the labels of sodium-glucose transporter 2 (SGLT2) inhibitors in December 2015 to inform users regarding the risk of diabetic ketoacidosis (DKA). As more drugs of this class are approved and their indications are expanded, this serious adverse effect has been increasingly reported.
OBJECTIVE
This review evaluated observational studies to inform the prevalence of SGLT2-inhibitor-associated DKA compared with other antihyperglycemic agents.
METHODS
A systematic review was conducted in PubMed and EMBASE until 19 July 2022 (PROSPERO: CRD42022385425). We included published retrospective cohort active comparator/new user (ACNU) and prevalent new user studies assessing SGLT2-inhibitor-associated DKA prevalence in adult patients with type 2 diabetes mellitus (T2DM) against active comparators. We excluded studies which lacked 1:1 propensity score matching. The JBI Checklist for Cohort Studies guided the risk-of-bias assessments. Meta-analysis was conducted based on the inverse variance method in R software.
RESULTS
Sixteen studies with a sample of 2,956,100 nonunique patients met the inclusion criteria. Most studies were conducted in North America (n = 9) and adopted the ACNU design (n = 15). Meta-analysis of 14 studies identified 33% higher DKA risk associated with SGLT2 inhibitors (HR = 1.33, 95% CI: 1.14-1.55, P < 0.01). Meta-regression analysis identified the study location (P = 0.02), analysis principle (P < 0.001), exclusion of chronic comorbidities (P = 0.007), and canagliflozin (P = 0.04) as significant moderator variables.
CONCLUSIONS
Despite limitations related to heterogeneity, generalizability, and misclassification, the results of this study show that SGLT2 inhibitors increase the prevalence of DKA among adult T2DM patients in the real world. The findings supplement evidence from randomized controlled trials (RCTs) and call for continued vigilance.
Topics: Adult; Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetic Ketoacidosis; Prevalence; Sodium-Glucose Transporter 2; Nimustine; Diabetes Mellitus, Type 2; Hypoglycemic Agents
PubMed: 37844733
DOI: 10.1016/j.japh.2023.10.010 -
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 -
International Urology and Nephrology Apr 2024Owing to the pharmacological mechanism, sodium-glucose cotransporter 2 inhibitors (SGLT2is) may be less effective in patients with reduced renal functions, but no... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Owing to the pharmacological mechanism, sodium-glucose cotransporter 2 inhibitors (SGLT2is) may be less effective in patients with reduced renal functions, but no systematic review or meta-analysis addressed chronic kidney disease (CKD) patients specifically. We aimed to assess the efficacy and safety of SGLT2is in CKD patients.
METHODS
We conducted a systematic review and meta-analysis of randomized controlled trials. Mean difference (MD) were pooled for the decline of glomerular filtration rate (eGFR) and change in urine albumin-to-creatinine ratio (uACR). Hazard ratio (HR) and rate ratio (RR) were pooled for composite of renal outcomes and adverse effects.
RESULTS
Thirty articles were identified. Overall MD in rate of eGFR decline was 0.02 (P = 0.05), with a borderline significant difference favoring SGLT2is, while the change in uACR from baseline was - 141.34 mg/g and hazard ratio of composite renal outcomes was 0.64 significantly favoring SGLT2is. Subgroup analyses showed that the long-term renal function, participants with baseline macroalbuminuria, and stage 4 CKD patients had significantly slower eGFR decline rate in SGLT2is compared to the placebo group. Risks of genital mycotic infection and ketoacidosis were significantly higher among the SGLT2is group than placebo.
CONCLUSION
For CKD patients, no matter diabetic or non-diabetic, our study showed potential renoprotective effects favoring SGLT2is in overall and long-term phase, and in patients with macroalbuminuria or stage 4 CKD. However, only slight increased risk of adverse effects among the SGLT2is group is observed. Therefore, we concluded that in CKD patients, prescribing SGLT2is was safe and had renal benefits.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Renal Insufficiency, Chronic; Glucose; Sodium
PubMed: 37752340
DOI: 10.1007/s11255-023-03789-6 -
Frontiers in Endocrinology 2023Immune checkpoint inhibitor (ICI)- and phosphatidylinositol-3-kinase inhibitor (PI3Ki)-related diabetes mellitus are common side effects of anti-tumor drug use that...
Immune checkpoint inhibitor (ICI)- and phosphatidylinositol-3-kinase inhibitor (PI3Ki)-related diabetes mellitus are common side effects of anti-tumor drug use that present mainly as hyperglycemia. Here, we present two case reports of diabetes mellitus caused by the use of tremelimumab and apalutamide, respectively, in cancer treatment, and a comprehensive, comparative review of the literature on these forms of diabetes. Case 1 presented with diabetic ketoacidosis and was diagnosed with ICI-related diabetes mellitus and treated with insulin. Case 2 was diagnosed with PI3Ki-related diabetes mellitus, and her blood glucose level returned to normal with the use of metformin and dapagliflozin. We systematically searched the PubMed database for articles on ICI- and PI3Ki-related diabetes mellitus and characterized the differences in clinical features and treatment between these two forms of diabetes.
Topics: Female; Humans; Antineoplastic Agents; Diabetes Mellitus; Diabetic Ketoacidosis; Hyperglycemia; Immune Checkpoint Inhibitors; Phosphatidylinositols
PubMed: 37732122
DOI: 10.3389/fendo.2023.1236946 -
World Journal of Clinical Cases Aug 2023Diabetic ketoacidosis (DKA) manifests as hyperglycemia, metabolic acidosis, and ketosis. However, euglycemic DKA (eu-DKA) conceals severe DKA with glucose levels below...
BACKGROUND
Diabetic ketoacidosis (DKA) manifests as hyperglycemia, metabolic acidosis, and ketosis. However, euglycemic DKA (eu-DKA) conceals severe DKA with glucose levels below 200 mg/dL. Sodium-glucose cotransporter-2 (SGLT2) inhibitors can induce eu-DKA in diabetic patients. Notably, coronavirus disease 2019 (COVID-19) -infected individuals with diabetes using SGLT2 inhibitors face an augmented risk of eu-DKA due to the direct toxic impact of the virus on pancreatic islets. This study aims to comprehensively investigate the association between SGLT2 inhibitors and eu-DKA in COVID-19 patients through meticulous case report analysis. Additionally, we endeavor to examine the outcomes and treatment approaches for COVID-19-infected diabetics receiving SGLT2 inhibitors, providing indispensable insights for healthcare professionals managing this specific patient population.
AIM
To investigate the connection between SGLT2 inhibitors and euglycemic DKA in COVID-19 patients through a meticulous analysis of case reports.
METHODS
We conducted an exhaustive search across prominent electronic databases, including PubMed, SCOPUS, Web of Science, and Google Scholar. This search encompassed the period from December 2019 to May 2022, incorporating published studies and pre-prints. The search terms employed encompassed "SGLT2 inhibitors", "euglycemic DKA", "COVID-19", and related variations. By incorporating these diverse sources, our objective was to ensure a thorough exploration of the existing literature on this subject, thereby augmenting the validity and robustness of our findings.
RESULTS
Our search yielded a total of seven case reports and one case series, collectively comprising a cohort of twelve patients. These reports detailed instances of eu-DKA in individuals with COVID-19. Crucially, all twelve patients were utilizing SGLT2 as their primary anti-diabetic medication. Upon admission, all oral medications were promptly discontinued, and the patients were initiated on intravenous insulin therapy to effectively manage the DKA. Encouragingly, eleven patients demonstrated a favorable outcome, while regrettably, one patient succumbed to the condition. Subsequently, SGLT2 were discontinued for all patients upon their discharge from the hospital. These findings provide valuable insights into the clinical management and outcomes of eu-DKA cases associated with COVID-19 and SGLT2, underscoring the critical importance of prompt intervention and vigilant medication adjustments.
CONCLUSION
Our study sheds light on the possibility of diabetic patients developing both drug-related and unrelated DKA, as well as encountering adverse outcomes in the context of COVID-19, despite maintaining satisfactory glycemic control. The relationship between glycemic control and clinical outcomes in COVID-19 remains ambiguous. Consequently, this systematic review proposes that COVID-19-infected diabetic patients using SGLT2 should contemplate alternative treatment protocols until their recovery from the disease.
PubMed: 37727728
DOI: 10.12998/wjcc.v11.i24.5700