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JAMA Network Open Dec 2022Patients with COVID-19 have a high prevalence of diabetes, and diabetes and blood glucose control are determinants of intensive care unit admission and mortality. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Patients with COVID-19 have a high prevalence of diabetes, and diabetes and blood glucose control are determinants of intensive care unit admission and mortality.
OBJECTIVE
To evaluate the association between COVID-19-related adverse outcomes and 8 antihyperglycemic drugs in patients with diabetes who were subsequently diagnosed and hospitalized with COVID-19.
DATA SOURCES
Data were retrieved and collected in PubMed, Embase, Cochrane Central Register, Web of Science, and ClinicalTrials.gov from database inception to September 5, 2022.
STUDY SELECTION
For this systematic review and network meta-analysis, randomized clinical trials and observational studies conducted among patients with diabetes while receiving glucose-lowering therapies for at least 14 days before the confirmation of COVID-19 infection were included after blinded review by 2 independent reviewers and consultations of disagreement by a third independent reviewer. Of 1802 studies initially identified, 31 observational studies met the criteria for further analysis.
DATA EXTRACTION AND SYNTHESIS
This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Bayesian network meta-analyses were performed with random effects.
MAIN OUTCOMES AND MEASURES
A composite adverse outcome, including the need for intensive care unit admission, invasive and noninvasive mechanical ventilation, or in-hospital death.
RESULTS
Thirty-one distinct observational studies (3 689 010 patients with diabetes hospitalized for COVID-19) were included. The sodium-glucose cotransporter-2 inhibitors (SGLT-2is) were associated with relatively lower risks of adverse outcomes compared with insulin (log of odds ratio [logOR], 0.91; 95% credible interval [CrI], 0.57-1.26), dipeptidyl peptidase-4 inhibitors (logOR, 0.61; 95% CrI, 0.28-0.93), secretagogues (logOR, 0.37; 95% CrI, 0.02-0.72), and glucosidase inhibitors (logOR, 0.50; 95% CrI, 0.00-1.01). Based on the surface under the cumulative ranking curves value, SGLT-2is were associated with the lowest probability for adverse outcomes (6%), followed by glucagon-like peptide-1 receptor agonists (25%) and metformin (28%). A sensitivity analysis revealed that the study was reliable.
CONCLUSIONS AND RELEVANCE
These findings suggest that the use of an SGLT-2i before COVID-19 infection is associated with lower COVID-19-related adverse outcomes. In addition to SGLT-2is, glucagon-like peptide-1 receptor agonists and metformin were also associated with relatively low risk of adverse outcomes.
Topics: Humans; Network Meta-Analysis; Glucose; COVID-19; Bayes Theorem; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Hospital Mortality; Sodium-Glucose Transporter 2 Inhibitors; Observational Studies as Topic
PubMed: 36472874
DOI: 10.1001/jamanetworkopen.2022.44652 -
Journal of Diabetes and Its... Jan 2023People with diabetes tend to face a higher risk of stroke. Randomized controlled trials (RCTs) have demonstrated the different outcomes of new glucose-lowering drugs... (Meta-Analysis)
Meta-Analysis Review
AIMS
People with diabetes tend to face a higher risk of stroke. Randomized controlled trials (RCTs) have demonstrated the different outcomes of new glucose-lowering drugs marketed in recent years on cardiovascular outcome events. The effects of glucagon-like peptide-1 (GLP-1) agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors on stroke risk were evaluated in published RCTs.
METHODS
A search of Embase, Cochrane Library, and PubMed databases identified studies with stroke as an outcome event up to 3 December 2021. Risk ratios for stroke outcomes were analyzed using a fixed-effects model. I was used to assess the heterogeneity of the study.
RESULTS
19 RCTs with 155,027 participants with type 2 diabetes were identified. Pooled analysis showed that compared to placebo, GLP-1 agonists reduced non-fatal stroke by 15 % (RR = 0.85, 95%CI 0.77-0.94, P = 0.002, I = 0 %) and total stroke (RR = 0.84, 95%CI 0.77-0.93, P = 0.000, I = 0 %) by 16 %. SGLT-2 inhibitors and DPP-4 inhibitors were not significantly associated with lower stroke risk.
CONCLUSIONS
This meta-analysis indicates that GLP-1 agonists have potential benefits for stroke. However, further studies are needed if GLP-1 agonists are to be used to reduce the risk of stroke in patients with type 2 diabetes. More research is also needed to investigate the effects of new glucose-lowering drugs on different stroke subtypes.
SYSTEMATIC REVIEW REGISTRATION
This protocol was registered on the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/PROSPERO/; registration number: CRD42022326382).
Topics: Humans; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Glucose; Hypoglycemic Agents; Stroke; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 36462459
DOI: 10.1016/j.jdiacomp.2022.108362 -
Molecular Neurodegeneration Nov 2022The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely... (Review)
Review
The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely resolved, they have been recognized for their signaling engagements and trafficking abilities, navigating a number of molecules between endosome, Golgi compartments, and the cell surface. Strikingly, recent studies connected all the VPS10p-D receptors to Alzheimer's disease (AD) development. In addition, they have been also associated with diseases comorbid with AD such as diabetes mellitus and major depressive disorder. This systematic review elaborates on genetic, functional, and mechanistic insights into how dysfunction in VPS10p-D receptors may contribute to AD etiology, AD onset diversity, and AD comorbidities. Starting with their functions in controlling cellular trafficking of amyloid precursor protein and the metabolism of the amyloid beta peptide, we present and exemplify how these receptors, despite being structurally similar, regulate various and distinct cellular events involved in AD. This includes a plethora of signaling crosstalks that impact on neuronal survival, neuronal wiring, neuronal polarity, and synaptic plasticity. Signaling activities of the VPS10p-D receptors are especially linked, but not limited to, the regulation of neuronal fitness and apoptosis via their physical interaction with pro- and mature neurotrophins and their receptors. By compiling the functional versatility of VPS10p-D receptors and their interactions with AD-related pathways, we aim to further propel the AD research towards VPS10p-D receptor family, knowledge that may lead to new diagnostic markers and therapeutic strategies for AD patients.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Depressive Disorder, Major; Protein Transport; Nerve Growth Factors
PubMed: 36397124
DOI: 10.1186/s13024-022-00576-2 -
Chemosphere Jan 2023Harmful algae blooms (HABs), caused by severe eutrophication and extreme weather, have spread all over the world, posing adverse effects on eco-environment and human... (Review)
Review
Harmful algae blooms (HABs), caused by severe eutrophication and extreme weather, have spread all over the world, posing adverse effects on eco-environment and human health. Microcystis aeruginosa is the dominant harmful cyanobacterial species when HABs occur, and the toxic metabolites produced by it, microcystins, are even fatal to humans. Photocatalytic technology has received wide attention from researchers for its clean and energy-efficient features, while the basic mechanisms and modification methods of photocatalysts have also been widely reported. In recent years, photocatalytic technology has shown great promise in the inhibition of HABs. In this article, we systematically reviewed the progress in photocatalytic performance and algae removal efficiency, discuss the damage mechanisms of photocatalysts for algae removal, including physical damage and various oxidative stresses, and also explore the degradation rates and possible pathways of microcystins. It can be concluded that during the photocatalytic process, the cytoarchitectural integrity of algae cells was damaged, a variety of important protein and enzyme systems were disrupted, and the antioxidant systems collapsed due to the continuous attack of ROS, which adversely affected the normal physiological activities and growth, resulting in the inactivation of algae cells. Moreover, photocatalysts have a degrading effect on microcystins, thus reducing the adverse effects of HAB. Finally, a brief summary of future research priorities regarding the photocatalytic degradation of algae cells is presented. This study helps to enhance the understanding of the destruction mechanism of Microcystis aeruginosa during the photocatalytic process, and provides a reference for the photodegradation of HAB in water bodies.
Topics: Humans; Microcystis; Microcystins; Harmful Algal Bloom; Antioxidants; Oxidative Stress
PubMed: 36379431
DOI: 10.1016/j.chemosphere.2022.137239 -
Biomolecules Oct 2022Alzheimer's disease (AD) is considered a chronic and debilitating neurological illness that is increasingly impacting older-age populations. Some proteins, including... (Review)
Review
Alzheimer's disease (AD) is considered a chronic and debilitating neurological illness that is increasingly impacting older-age populations. Some proteins, including clusterin ( or ) transporter, can be linked to AD, causing oxidative stress. Therefore, its activity can affect various functions involving complement system inactivation, lipid transport, chaperone activity, neuronal transmission, and cellular survival pathways. This transporter is known to bind to the amyloid beta (Aβ) peptide, which is the major pathogenic factor of AD. On the other hand, this transporter is also active at the blood-brain barrier (BBB), a barrier that prevents harmful substances from entering and exiting the brain. Therefore, in this review, we discuss and emphasize the role of the transporter and -linked molecular mechanisms at the BBB interface in the pathogenesis of AD.
Topics: Humans; Clusterin; Alzheimer Disease; Amyloid beta-Peptides; Blood-Brain Barrier; Membrane Transport Proteins; Lipids
PubMed: 36291661
DOI: 10.3390/biom12101452 -
BMC Endocrine Disorders Oct 2022Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular adverse events of sulfonylureas and drugs with a low risk for hypoglycaemia in adults with type 2 diabetes.
METHODS
Systematic review and meta-analysis of randomised controlled trials.
DATA SOURCES
MEDLINE (PubMed, OVID), Embase, Cochrane Central Register of Controlled Trials, CINAHL, WOS and Lilacs.
STUDY SELECTION
Randomised controlled head-to-head trials that compared sulfonylureas with active control with low hypoglycaemic potential in adults (≥ 18 years old) with type 2 diabetes published up to August 2015. The drug classes involved in the analysis were metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists.
OUTCOMES
The primary endpoint was all-cause mortality. The secondary endpoints were MACE, cardiovascular events and severe hypoglycaemia.
SYNTHESIS OF RESULTS
Two reviewers checked study eligibility, independently extracted data and assessed quality with disagreements resolved through discussion. We assessed the risk of bias of the included studies using the Cochrane risk of bias tool for randomized trials v2. Pooled odds ratios (ORs) were estimated by using fixed effects model. The study is registered on PROSPERO (26/05/2016 CRD42016038780).
RESULTS
Our final analysis comprised 31 studies (26,204 patients, 11,711 patients given sulfonylureas and 14,493 given comparator drugs). In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07-1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17-2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20-6.55). Subsequent sensitivity analysis revealed differences in the effect of sulfonylureas, with an increased risk of all-cause mortality with glipizide but not the other molecules.
CONCLUSION
Our meta-analysis raises concern about the safety of SUs compared to alternative drugs involved in current analysis. Important differences may exist within the drug class, and glimepiride seems to have best safety profile.
Topics: Adult; Humans; Adolescent; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Glipizide; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sodium-Glucose Transporter 2 Inhibitors; Hypoglycemia; Glucagon-Like Peptide 1; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Symporters; Glucose; Sodium
PubMed: 36261824
DOI: 10.1186/s12902-022-01158-5 -
Theriogenology Nov 2022Reproductive traits, such as the number of teats and litter size, are essential for animal breeding programs due to the importance of the production chain, since they...
Reproductive traits, such as the number of teats and litter size, are essential for animal breeding programs due to the importance of the production chain, since they influence the maternal ability of the sow and can affect the number of weaned piglets. We aim to identify candidate genes associated with reproductive traits in pigs, using GWAS data from a systematic review combined with sequencing data, to build networks of biological processes and transcription factors (TFs) from the identified genes to highlight the most candidate genes for litter size and the number of teats. In the systematic review, only peer-reviewed articles were used, with descriptors related to the evaluated traits, and selected based on eligibility criteria. Fourteen papers were selected and classified for functional analysis of gene networks with 2077 candidate genes identified. After combining with the list of genes presenting known structural variants in the 5'UTR and/or coding region, 306 genes remained to be used to build the gene networks of biological processes and TFs, highlighting processes associated with litter size (e.g., ionotropic glutamate receptor signaling pathway and blastocyte growth) and the number of teats (e.g., growth hormone receptor, regulation of the BMP - Bone Morphogenetic Proteins signaling pathway and blood vessel proliferation). Two most candidate genes for litter size trait (GRID2 and PALB2) and six most candidate genes for the number of teats (GHR, IFT80, FSTL3, SKOR1, SMURF1, and AKT3) were prioritized. TFs associated with candidate genes were also identified for litter size (PALB2 and GRID2) and the number of teats (RIN, LTBP2, and COL6A6). Thus, it is suggested that the most candidate genes and TFs presented in this study may play an important role in the traits studied, being important for genetic studies and animal breeding.
Topics: 5' Untranslated Regions; Animals; Bone Morphogenetic Proteins; Female; Genome-Wide Association Study; Litter Size; Phenotype; Polymorphism, Single Nucleotide; Pregnancy; Receptors, Ionotropic Glutamate; Receptors, Somatotropin; Swine; Transcription Factors
PubMed: 36209572
DOI: 10.1016/j.theriogenology.2022.09.005 -
Clinical Pharmacokinetics Nov 2022An ever-growing body of evidence supports the impact of cytokine modulation on the patient's phenotypic drug response. The aim of this systematic review was to analyze... (Review)
Review
The Cytokine Release Syndrome and/or the Proinflammatory Cytokines as Underlying Mechanisms of Downregulation of Drug Metabolism and Drug Transport: A Systematic Review of the Clinical Pharmacokinetics of Victim Drugs of this Drug-Disease Interaction Under Different Clinical Conditions.
BACKGROUND AND OBJECTIVE
An ever-growing body of evidence supports the impact of cytokine modulation on the patient's phenotypic drug response. The aim of this systematic review was to analyze the clinical studies that assessed the pharmacokinetics of victim drugs of this drug-disease interaction in the presence of different scenarios of cytokine modulation in comparison with baseline conditions.
METHODS
We conducted a systematic review by searching the PubMed-MEDLINE database from inception until February 2022 to retrieve prospective and/or retrospective observational studies, population pharmacokinetic studies, phase I studies, and/or case series/reports that investigated the impact of cytokine modulation on the pharmacokinetic behavior of victim drugs. Only studies providing quantitative pharmacokinetic data of victim drugs by comparing normal status versus clinical conditions with documented cytokine modulation or by assessing the influence of anti-inflammatory biological agents on metabolism and/or transport of victim drugs were included.
RESULTS
Overall, 26 studies were included. Rheumatoid arthritis (6/26; 23.1%) and sepsis (5/26; 19.2%) were the two most frequently investigated pro-inflammatory clinical scenarios. The victim drug most frequently assessed was midazolam (14/26; 53.8%; as a probe for cytochrome P450 [CYP] 3A4). Cytokine modulation showed a moderate inhibitory effect on CYP3A4-mediated metabolism (area under the concentration-time curve increase and/or clearance decrease between 1.98-fold and 2.59-fold) and a weak-to-moderate inhibitory effect on CYP1A2, CYP2C9, and CYP2C19-mediated metabolism (in the area under the concentration-time curve increase or clearance decrease between 1.29-fold and 1.97-fold). Anti-interleukin-6 agents showed remarkable activity in counteracting downregulation of CYP3A4-mediated activity (increase in the area under the concentration-time curve between 1.75-fold and 2.56-fold).
CONCLUSIONS
Cytokine modulation may cause moderate or weak-to-moderate downregulation of metabolism/transport of victim drugs, and this may theoretically have relevant clinical consequences.
Topics: Humans; Cytochrome P-450 CYP3A; Cytokine Release Syndrome; Cytokines; Down-Regulation; Prospective Studies; Retrospective Studies; Drug Interactions
PubMed: 36059001
DOI: 10.1007/s40262-022-01173-8 -
The Canadian Journal of Cardiology Aug 2022Evidence for the cardiorenal risk reduction properties of antihyperglycemic medications originally prescribed for type 2 diabetes, sodium-glucose cotransporter 2... (Meta-Analysis)
Meta-Analysis Review
The Effectiveness of Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists on Cardiorenal Outcomes: Systematic Review and Meta-analysis.
BACKGROUND
Evidence for the cardiorenal risk reduction properties of antihyperglycemic medications originally prescribed for type 2 diabetes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) is rapidly emerging. We completed a meta-analysis of recent literature to provide evidence-based estimates of benefit across various populations and outcomes.
METHODS
We searched Medline and Cochrane databases from 2015 to September 2021 for randomized controlled trials of SGLT2i and GLP-1RA with placebo control. Reviewers screened citations, extracted data, and assessed the risk of bias and certainty of evidence. We assessed statistical and methodological heterogeneity and performed a meta-analysis of studies with similar interventions and components.
RESULTS
A total of 137,621 adults (51% male) from 19 studies were included; 14 studies with unclear risk of bias and 5 with low risk of bias. Compared with standard of care, use of SGLT2i showed significant reductions for the outcome of cardiovascular (CV) mortality (14%), any-cause mortality (13%), major adverse CV events (MACE) (12%), heart failure (HF) hospitalization (31%), CV death or HF hospitalization (24%), nonfatal myocardial infarction (10%), and kidney composite outcome (36%). Treatment with GLP-1RA was associated with significant reductions for the outcome of CV mortality (13%), any-cause mortality (12%), MACE (14%), CV death or HF hospitalization (11%), nonfatal stroke (16%), and kidney composite outcome (22%).
CONCLUSIONS
The use of GLP-1RA and SGLT2i leads to a statistically significant benefit across most cardiorenal outcomes in the populations studied. This review shows a role for SGLT2i and GLP-1RA in cardiorenal protection in adults, independent of type 2 diabetes status.
Topics: Adult; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Hypoglycemic Agents; Male; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35961756
DOI: 10.1016/j.cjca.2022.05.011 -
Diabetes Research and Clinical Practice Sep 2022Current guidelines recommend insulin alone for in-hospital management of diabetes, but growing information suggests that new oral or injectable agents may be as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Current guidelines recommend insulin alone for in-hospital management of diabetes, but growing information suggests that new oral or injectable agents may be as effective and safe.
METHODS
Systematic review and meta-analysis with evidence from randomized (RCT) and non-randomized (NRS) studies in PubMed, EMBASE and LILACS databases up to February 10, 2022, for studies including hospitalized type 2 diabetes patients, comparing dipeptidyl peptidase 4 inhibitors (DPP4i), sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP1Ra) with insulin alone for glycemic control and safety outcomes.
FINDINGS
7 RCT and 3 NRTs were included. There were no differences in mean blood glucose, measurements within range or rate of hypoglycemia between DPP4i and insulin. We found a lower mean glucose for GLP1Ra plus insulin subgroup (-16.36 mg/dL, 95 % CI -27.31, -5.41; I = 0 %) with lower incidence of hypoglycemia < 70 mg/dL with GLP1Ra (RR 0.31, CI 95 % 0.14-0.70, I = 0 %). SGLT2i data was limited. Adverse events rates were similar between treatments.
CONCLUSION
Our review suggests that inpatient management in the general ward with DPP4i and GLP1Ra is as effective and safe as management with insulin. More randomized studies are required to support these findings before they could be recommended as usual practice.
Topics: Blood Glucose; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide-1 Receptor; Hospitalization; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Sodium; Sodium-Glucose Transporter 2 Inhibitors; Symporters
PubMed: 35931222
DOI: 10.1016/j.diabres.2022.110019