Pharmacogenomics. 2023 May 24. doi: 10.2217/pgs-2023-0029. Online ahead of print.

ABSTRACT

Aim: The indigenous Arab population is underrepresented in genomic studies and the landscape of actionable pharmacogenomic variants among Arab breast cancer patients remains unclear. Materials & methods: Exome sequencing was performed on 220 unselected Arab female breast cancer patients and germline variants in CYP2D6 and DPYD were profiled using a deep learning method. Results: In total, 13 (5.9%) patients had clinically actionable results and 56 (25.5%) carried an allele in DYPD or CYP2D6 with unknown impact on drug metabolism. In addition, four unique novel missense variants were discovered, including one in CYP2D6 (p.Arg64Leu) with high predicted pathogenicity. Conclusion: A nontrivial subset of Arab breast cancer patients can potentially benefit from pretreatment molecular profiling, and further study is needed to improve characterization of the pharmacogenomic landscape.

PMID:37222147 | DOI:10.2217/pgs-2023-0029

Pharmacogenomics. 2023 May 24. doi: 10.2217/pgs-2023-0071. Online ahead of print.

NO ABSTRACT

PMID:37222126 | DOI:10.2217/pgs-2023-0071

Basic Clin Pharmacol Toxicol. 2023 May 23. doi: 10.1111/bcpt.13903. Online ahead of print.

ABSTRACT

CYP2D6 is an important drug metabolizing enzyme exhibiting extensive interindividual variability predominantly caused by genetic polymorphism. Predicting CYP2D6 function based on genotype may be used to personalize pharmacotherapy, but the process of translating CYP2D6 genotype into predicted phenotype is complex and has suffered from a lack of consensus. The Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group have proposed a standardized translation scheme based on the activity score system aiming to facilitate more consistent CYP2D6 genotype-phenotype translation. However, this system remains suboptimal particularly with regards to decreased function alleles and substrate-specific behaviour. This review summarizes the process and challenges for functional assignment of CYP2D6 alleles. We discuss population pharmacokinetics (popPK) as a tool for estimating CYP2D6 function and present findings from three popPK meta-analyses quantifying the impact of individual CYP2D6 alleles in the metabolism of vortioxetine, tedatioxetine and brexpiprazole. Findings from these analyses indicate that the activity values currently assigned to decreased function alleles CYP2D6*9, *17 and *41 overestimate their function. Moreover, the CYP2D6*2 allele exhibited reduced activity in the metabolism of brexpiprazole indicating substrate-specific behaviour. Considering the totality of evidence, the activity score system may be further refined to better reflect the enzyme function associated with these alleles.

PMID:37221697 | DOI:10.1111/bcpt.13903

Pharmacogenomics J. 2023 May 23. doi: 10.1038/s41397-023-00307-w. Online ahead of print.

ABSTRACT

BACKGROUND: Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity.

METHODS: The Genes & Health cohort consists of British-Bangladeshi and British-Pakistani participants from East London, Manchester and Bradford, UK. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not.

RESULTS: Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)).

CONCLUSIONS: Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.

PMID:37221222 | DOI:10.1038/s41397-023-00307-w

J Med Genet. 2023 May 22:jmg-2022-109091. doi: 10.1136/jmg-2022-109091. Online ahead of print.

ABSTRACT

Secondary findings (SFs) identified through genomic sequencing (GS) can offer a wide range of health benefits to patients. Resource and capacity constraints pose a challenge to their clinical management; therefore, clinical workflows are needed to optimise the health benefits of SFs. In this paper, we describe a model we created for the return and referral of all clinically significant SFs, beyond medically actionable results, from GS. As part of a randomised controlled trial evaluating the outcomes and costs of disclosing all clinically significant SFs from GS, we consulted genetics and primary care experts to determine a feasible workflow to manage SFs. Consensus was sought to determine appropriate clinical recommendations for each category of SF and which clinician specialist would provide follow-up care. We developed a communication and referral plan for each category of SFs. This involved referrals to specialised clinics, such as an Adult Genetics clinic, for highly penetrant medically actionable findings. Common and non-urgent SFs, such as pharmacogenomics and carrier status results for non-family planning participants, were directed back to the family physician (FP). SF results and recommendations were communicated directly to participants to respect autonomy and to their FPs to support follow-up of SFs. We describe a model for the return and referral of all clinically significant SFs to facilitate the utility of GS and promote the health benefits of SFs. This may serve as a model for others returning GS results transitioning participants from research to clinical settings.

PMID:37217257 | DOI:10.1136/jmg-2022-109091

Indian Heart J. 2023 May 20:S0019-4832(23)00088-3. doi: 10.1016/j.ihj.2023.05.005. Online ahead of print.

ABSTRACT

BACKGROUND: It is essential to investigate the prevalence of CYP2C19 alleles that affect drug metabolism. This study measures the allelic and genotypic frequencies of CYP2C19 loss-of-function (LoF) alleles CYP2C19*2, CYP2C19*3, and gain-of-function (GoF) alleles CYP2C19*17 in the general population.

METHODOLOGY: The study involved 300 healthy subjects between the ages of 18 and 85 recruited by simple random sampling. Allele-specific touchdown PCR was employed to identify the various alleles. The genotype and allele frequencies were calculated and checked for Hardy-Weinberg equilibrium. The phenotypic prediction of ultra-rapid metabolizer (UM = *17/*17), extensive metabolizer (EM = *1/*17, *1/*1), intermediate metabolizer (IM = *1/*2, *1/*3, *2/*17) and poor metabolizer (PM = *2/*2, *2/*3, *3/*3) was made based on their genotype.

RESULTS: The allele frequency of CYP2C19*2, CYP2C19*3, and CYP2C19*17 was 0.365, 0.0033, and 0.18, respectively. The IM phenotype predominated with an overall frequency of 46.67%, including 101 subjects with *1/*2, two subjects with *1/*3, and 37 subjects with *2/*17 genotype. This was followed by EM phenotype with an overall frequency of 35%, including 35 subjects with *1/*17 and 70 subjects with *1/*1 genotype. PM phenotype had an overall frequency of 12.67%, including 38 subjects with *2/*2 genotype, and UM phenotype had an overall frequency of 5.67%, including 17 subjects with *17/*17 genotype.

CONCLUSION: Given the high allelic frequency of PM in the study population, a pre-treatment test to identify the individual's genotype may be recommended to decide the dosage, monitor the drug response, and avoid adverse drug reactions.

PMID:37217095 | DOI:10.1016/j.ihj.2023.05.005

Xenobiotica. 2023 May 22:1-28. doi: 10.1080/00498254.2023.2217506. Online ahead of print.

ABSTRACT

Delayed-release dimethyl fumarate (DMF), Tecfidera®, is approved globally for treating relapsing-remitting multiple sclerosis. The disposition of DMF was determined in humans after administration of a single oral dose of [14C]DMF, and the total recovery was estimated to be between 58.4% to 75.0%, primarily through expired air.The absorption of [14C]DMF-derived radioactivity was rapid, with Tmax at 1h postdose. Glucose was the predominant circulating metabolite, accounting for ∼60% of the total extractable radioactivity. Cysteine and N-acetylcysteine conjugates of mono- or di-methyl succinate were found to be the major urinary metabolites.In vitro studies showed that [14C]DMF was mainly metabolized to MMF, and fumarase exclusively converted fumaric acid to malic acid and did not catalyze the conversion of fumaric acid esters to malic acid. DMF was observed to bind with human serum albumin through Michael addition to the Cys-34 residue when exposed to human plasma.These findings indicate that DMF undergoes metabolism via hydrolysis, GSH conjugation, and the TCA cycle, leading to the formation of citric acid, CO2, and water. These ubiquitous and well-conserved metabolism pathways minimize the risk of drug-drug interactions and reduce variability related to pharmacogenetics and ethnicity.

PMID:37216617 | DOI:10.1080/00498254.2023.2217506

PEC Innov. 2022 Dec 16;2:100119. doi: 10.1016/j.pecinn.2022.100119. eCollection 2023 Dec.

ABSTRACT

OBJECTIVE: To examine the impact of various presentations of pharmacogenomic testing results using a published, color-coded decision support tool (DST) format as a standard stimulus to list possible medications.

METHODS: Participants were randomly assigned to groups and asked to decide which psychotropic medication they would prefer if depressed. Three of the groups varied the color-coded category of fluoxetine and received a statement indicating that this was the most prescribed drug for depression. A fourth control condition omitted base rate information. Participants also provided detail about their decision-making processes through a qualitative interview.

RESULTS: Comparison of the first three groups indicated that significantly more participants selected medications from the highest category of likely effectiveness when fluoxetine appeared in this list. Comparison of the control group to its relevant analogue suggested no significant differences in selection strategy. Qualitative interview responses indicated participant comfort with genetic testing despite awareness of having very limited understanding of these techniques and their implications.

CONCLUSIONS: Both DST color-coding and base rates were influential in driving drug selection decisions, despite most participants indicating they did not understand this information.

INNOVATION: Efforts to standardize pharmacogenomic stimuli may lead to advances in methods of studying quantifiable healthcare decisions. Attention to the context for presenting test results may also be a useful source of understanding patient responses, particularly regarding complex tests that are likely to be interpreted heuristically.

PMID:37214496 | PMC:PMC10194257 | DOI:10.1016/j.pecinn.2022.100119

Front Genet. 2023 May 5;14:1152585. doi: 10.3389/fgene.2023.1152585. eCollection 2023.

ABSTRACT

Unexpected poor efficacy and intolerable adverse effects are medication-related problems that may result from genetic variation in genes encoding key proteins involved in pharmacokinetics or pharmacodynamics. Pharmacogenomic (PGx) testing can be used in medical practice "pre-emptively" to avoid future patient harm from medications and "reactively" to diagnose medication-related problems following their occurrence. A structured approach to PGx consulting is proposed to calculate the pharmacogenomics benefit score (PGxBS), a patient-centered objective measure of congruency between medication-related problems and patient genotypes. An example case of poor efficacy with multiple medications is presented, together with comments on the potential benefits and limitations of using the PGxBS in medical practice.

PMID:37214415 | PMC:PMC10196203 | DOI:10.3389/fgene.2023.1152585

Pharmacogenomics. 2023 May 22. doi: 10.2217/pgs-2022-0171. Online ahead of print.

ABSTRACT

Aim: To assess the role of genetic polymorphisms in postoperative imatinib concentrations and edema in patients with gastrointestinal stromal tumor. Methods: The relationships between genetic polymorphisms, imatinib concentrations and edema were explored. Results: Carriers of the rs683369 G-allele and rs2231142 T-allele had significantly higher imatinib concentrations. Grade ≥2 periorbital edemas were related to the carriership of two C-alleles in rs2072454 with an adjusted odds ratio of 2.85, two T-alleles in rs1867351 with an adjusted odds ratio of 3.42 and two A-alleles in rs11636419 with an adjusted odds ratio of 3.15. Conclusion: rs683369 and rs2231142 affect the metabolism of imatinib; rs2072454, rs1867351 and rs11636419 are related to grade ≥2 periorbital edemas.

PMID:37212851 | DOI:10.2217/pgs-2022-0171

J Appl Biomed. 2023 May 4. doi: 10.32725/jab.2023.006. Online ahead of print.

ABSTRACT

INTRODUCTION: Thymoquinone (TQ) is one of the bioactive compounds in Nigella sativa (NS). Also known as black seeds/cumin, it has been postulated to possess anti-atherogenic properties. However, research on the effects of NS oil (NSO) and TQ on atherogenesis remain scarce. The aim of this study is to determine gene and protein expression of Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), and Endothelial-eukocyte adhesion molecule (E-selectin) in Human Coronary Artery Endothelial Cells (HCAECs).

METHODS: HCAECs were stimulated for 24 hours (h) with 200 µg/ml of Lipopolysaccharides (LPS) and different concentrations of NSO (55, 110, 220, 440 µg/ml) or TQ (4.5, 9.0, 18.0, 36.0 µm). The effects of NSO and TQ on gene and protein expressions were measured using multiplex gene assay and ELISA assay, respectively. Rose Bengal assay was used to analyse monocyte binding activity.

RESULTS: NSO and TQ significantly reduced ICAM-1 and VCAM-1 gene and protein expressions. TQ showed significant reduction activity of the biomarkers in dose dependent manner. HCAECs pre-treated with NSO and TQ for 24 h significantly lowered monocytes adherence compared to non-treated HCAECs.

CONCLUSIONS: NSO and TQ supplementation have anti-atherogenic properties and inhibit monocytes' adherence to HCAECs via down-regulation of ICAM-1 expression. NSO could potentially be incorporated in standard treatment regimens to prevent atherosclerosis and its related complications.

PMID:37212154 | DOI:10.32725/jab.2023.006

Clin Gastroenterol Hepatol. 2023 May 19:S1542-3565(23)00377-4. doi: 10.1016/j.cgh.2023.05.007. Online ahead of print.

NO ABSTRACT

PMID:37211267 | DOI:10.1016/j.cgh.2023.05.007

Biochem Pharmacol. 2023 May 19:115616. doi: 10.1016/j.bcp.2023.115616. Online ahead of print.

ABSTRACT

Cancer stem cells (CSCs) are the leading cause of recurrence and poor prognosis in non-small cell lung cancer (NSCLC). Eukaryotic translation initiation factor 3a (eIF3a) participates in many tumor development processes, such as metastasis, therapy resistance, and glycolysis, all of which are closely associated with the presence of CSCs. However, whether eIF3a maintains NSCLC-CSC-like properties remains to be elucidated. In this study, eIF3a was highly expressed in lung cancer tissues and was linked to poor prognosis. eIF3a was also highly expressed in CSC-enriched spheres compared with adherent monolayer cells. Moreover, eIF3a is required for NSCLC stem cell-like traits maintenance in vitro and in vivo. Mechanistically, eIF3a activates the Wnt/β-catenin signaling pathway, promoting the transcription of cancer stem cell markers. Specifically, eIF3a promotes the transcriptional activation of β-catenin and mediates its nuclear accumulation to form a complex with T cell factor 4 (TCF4). However, eIF3a has no significant effect on protein stability and translation. Proteomics analysis revealed that the candidate transcription factor, Yin Yang 1 (YY1), mediates the activated effect of eIF3a on β-catenin. Overall, the findings of this study implied that eIF3a contributes to the maintenance of NSCLC stem cell-like characteristics through the Wnt/β-catenin pathway. eIF3a is a potential target for the treatment and prognosis of NSCLC.

PMID:37211173 | DOI:10.1016/j.bcp.2023.115616

Am J Health Syst Pharm. 2023 May 21:zxad111. doi: 10.1093/ajhp/zxad111. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: To describe the implementation of clinical decision support tools for alerting prescribers of actionable drug-gene interactions in the Veterans Health Administration (VHA).

SUMMARY: Drug-gene interactions have been the focus of clinicians for years. Interactions between SCLO1B1 genotype and statin medications are of particular interest as these can inform risk for statin-associated muscle symptoms (SAMS). VHA identified approximately 500,000 new users of statin medications prescribed in VHA in fiscal year 2021, some of whom could benefit from pharmacogenomic testing for the SCLO1B1 gene. In 2019, VHA implemented the Pharmacogenomic Testing for Veterans (PHASER) program to offer panel-based, preemptive pharmacogenomic testing and interpretation. The PHASER panel includes SLCO1B1, and VHA utilized Clinical Pharmacogenomics Implementation Consortium statin guidelines to build its clinical decision support tools. The program's overarching goal is to reduce the risk of adverse drug reactions such as SAMS and improve medication efficacy by alerting practitioners of actionable drug-gene interactions. We describe the development and implementation of decision support for the SLCO1B1 gene as an example of the approach being used for the nearly 40 drug-gene interactions screened for by the panel.

CONCLUSION: The VHA PHASER program identifies and addresses drug-gene interactions as an application of precision medicine to reduce veterans' risks for adverse events. The PHASER program's implementation of statin pharmacogenomics utilizes a patient's SCLO1B1 phenotype to alert providers of the risk for SAMS with the statin being prescribed and how to lower that risk through a lower dose or alternative statin selection. The PHASER program may help reduce the number of veterans who experience SAMS and may improve their adherence to statin medications.

PMID:37210707 | DOI:10.1093/ajhp/zxad111

Exp Biol Med (Maywood). 2023 May 19:15353702231165025. doi: 10.1177/15353702231165025. Online ahead of print.

ABSTRACT

One of the unsolved mysteries of medicine is how do volatile anesthetics (VAs) cause a patient to reversibly lose consciousness. In addition, identifying mechanisms for the collateral effects of VAs, including anesthetic-induced neurotoxicity (AiN) and anesthetic preconditioning (AP), has proven challenging. Multiple classes of molecules (lipids, proteins, and water) have been considered as potential VA targets, but recently proteins have received the most attention. Studies targeting neuronal receptors or ion channels had limited success in identifying the critical targets of VAs mediating either the phenotype of "anesthesia" or their collateral effects. Recent studies in both nematodes and fruit flies may provide a paradigm shift by suggesting that mitochondria may harbor the upstream molecular switch activating both primary and collateral effects. The disruption of a specific step of electron transfer within the mitochondrion causes hypersensitivity to VAs, from nematodes to Drosophila and to humans, while also modulating the sensitivity to collateral effects. The downstream effects from mitochondrial inhibition are potentially legion, but inhibition of presynaptic neurotransmitter cycling appears to be specifically sensitive to the mitochondrial effects. These findings are perhaps of even broader interest since two recent reports indicate that mitochondrial damage may well underlie neurotoxic and neuroprotective effects of VAs in the central nervous system (CNS). It is, therefore, important to understand how anesthetics interact with mitochondria to affect CNS function, not just for the desired facets of general anesthesia but also for significant collateral effects, both harmful and beneficial. A tantalizing possibility exists that both the primary (anesthesia) and secondary (AiN, AP) mechanisms may at least partially overlap in the mitochondrial electron transport chain (ETC).

PMID:37208922 | DOI:10.1177/15353702231165025

Brain Behav. 2023 May 19:e2799. doi: 10.1002/brb3.2799. Online ahead of print.

ABSTRACT

BACKGROUND: Galcanezumab is a monoclonal antibody acting against the calcitonin gene-related peptide approved for the preventive treatment of migraine. The aim of this article is to explore its effectiveness and safety of galcanezumab in chronic migraine (CM) with medication overuse-headache (MOH).

METHODS: Seventy-eight patients were consecutively enrolled at the Modena headache center and followed up for 15 months. Visits were scheduled every 3 months, and the following variables were collected: the number of migraine days per month (MDM); the painkillers taken per month (PM); the number of days per month in which the patient took, at least, one painkiller; the six-item headache impact test; and the migraine disability assessment questionnaire (MIDAS) score. Demographic features of the analyzed sample were collected at the baseline and adverse events (AEs) were collected at every visit.

RESULTS: After 12 months, galcanezumab significantly reduced the MDM, the PM, the number of days on medication, the HIT-6 as well as the MIDAS scores (all p < .0001). The greatest amelioration was obtained in the first trimester of treatment. A higher MDM, a higher NRS score at the baseline, and a higher number of failed preventive treatments negatively predict the CM relief at the year of treatment. No serious AEs were registered and only one drop-out was due to AE.

CONCLUSIONS: Galcanezumab is effective and safe for the treatment of patients affected by CM and MOH. Patients with a higher impairment at the baseline may found less benefits with galcanezumab.

PMID:37208838 | DOI:10.1002/brb3.2799

Trials. 2023 May 19;24(1):342. doi: 10.1186/s13063-023-07361-6.

ABSTRACT

BACKGROUND: The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs.

METHODS: The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18-65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention.

DISCUSSION: This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care.

TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021.

PMID:37208772 | DOI:10.1186/s13063-023-07361-6

J Psychiatry Neurosci. 2023 May 19;48(3):E179-E189. doi: 10.1503/jpn.220206. Print 2023 May-Jun.

ABSTRACT

BACKGROUND: Tourette syndrome is a developmental neuropsychiatric disorder. Its etiology is complex and elusive, although an important role of genetic factors has been established. The aim of the present study was to identify the genomic basis of Tourette syndrome in a group of families with affected members in 2 or 3 generations.

METHODS: Whole-genome sequencing was performed followed by co-segregation and bioinformatic analyses. Identified variants were used to select candidate genes, which were then subjected to gene ontology and pathway enrichment analysis.

RESULTS: The study group included 17 families comprising 80 patients with Tourette syndrome and 44 healthy family members. Co-segregation analysis and subsequent prioritization of variants pinpointed 37 rare and possibly pathogenic variants shared among affected individuals within a single family. Three such variants, in the ALDH2, DLD and ALDH1B1 genes, could influence oxidoreductase activity in the brain. Two variants, in SLC17A8 and BSN genes, were involved in sensory processing of sound by inner hair cells of the cochlea. Enrichment analysis of genes whose rare variants were present in all patients from at least 2 families identified significant gene sets implicated in cell-cell adhesion, cell junction assembly and organization, processing of sound, synapse assembly, and synaptic signalling processes.

LIMITATIONS: We did not examine intergenic variants, but they still could influence clinical phenotype.

CONCLUSION: Our results provide a further argument for a role of adhesion molecules and synaptic transmission in neuropsychiatric diseases. Moreover, an involvement of processes related to oxidative stress response and sound-sensing in the pathology of Tourette syndrome seems likely.

PMID:37208127 | DOI:10.1503/jpn.220206

Cureus. 2023 Apr 17;15(4):e37708. doi: 10.7759/cureus.37708. eCollection 2023 Apr.

ABSTRACT

Diabetes is one of the most common chronic ailments; its incidence has reached epidemic proportions in the 21st century. Diabetes significantly increases micro and macrovascular complications, which are effectively managed with statins. Therefore, statins' pharmacokinetics, pharmacodynamics, and pharmacogenetics have been extensively studied. Although statins act as a keystone in preventing cardiovascular complications, at the same time, they pose a threat to the quality of life of diabetics due to the resulting muscular side effects. This article summarizes the prevalence, clinical manifestations, pathophysiology, and risk factors of statin-induced myopathy in diabetic patients. Among the diverse predisposing risk factors, the primary variables identified for causing myopathy in diabetic patients include age, gender, ethnicity, duration and severity of illness, comorbid conditions, level of physical activity, alcohol use, cholecalciferol (vitamin D3) levels, type and dose of statins, and anti-diabetic drugs or other drugs used concomitantly. In addition, cardiovascular risk quotients also potentially impact diabetic patients making them more vulnerable to developing myopathy from statins. Therefore, this study highlights the importance of managing statin-associated myopathic side effects by providing consensus guidelines on diagnostic, monitoring, and treatment strategies. We also discussed statins' prognostic value in reducing cardiovascular events in diabetic individuals.

PMID:37206522 | PMC:PMC10191392 | DOI:10.7759/cureus.37708

Front Pharmacol. 2023 May 3;14:1211712. doi: 10.3389/fphar.2023.1211712. eCollection 2023.

NO ABSTRACT

PMID:37205907 | PMC:PMC10189108 | DOI:10.3389/fphar.2023.1211712