Risk Of New-onset Diabetes Mellitus Research Articles

Different diabetogenic effect of statins according to intensity and dose in patients with acute myocardial infarction: a nationwide cohort study

Statin is crucial for acute myocardial infarction (AMI) patients. However, the risk of new-onset diabetes mellitus (NODM) associated with statin is a concern. This study aimed to determine the incremental diabetogenic effects of statins according to their intensity and dose in AMI patients undergoing percutaneous coronary intervention (PCI). Among 13,104 patients enrolled in the Korea AMI Registry between 2011 and 2015, 6152 patients without diabetes mellitus (DM) who underwent PCI and received moderate-to-high-intensity atorvastatin and rosuvastatin were selected for the study. The endpoints were NODM and major adverse cardiovascular events (MACE), composite of all-cause mortality, recurrent MI, and revascularization up to 3 years. Among the participants, 3747 and 2405 received moderate- and high-intensity statins, respectively. The Kaplan–Meier curves demonstrated a higher incidence of NODM in patients with high-intensity statins than those with moderate-intensity. High-intensity statin was a significant predictor of NODM after adjusting for other co-variables (HR = 1.316, 95% CI 1.024–1.692; P < 0.032). Higher dose of rosuvastatin was associated with a higher cumulative incidence of NODM, but this dose-dependency was not apparent with atorvastatin. Cumulative incidence of MACE decreased dose-dependently only with atorvastatin. High-intensity statin was associated with a higher cumulative incidence of NODM in AMI patients, and this association was more evident in rosuvastatin. The different diabetogenic effects of the two statins provide supporting evidence for understanding the nuanced nature of statin treatment in relation to NODM.

Effect of rosuvastatin versus atorvastatin on new-onset diabetes mellitus in patients treated with high-intensity statin therapy for coronary artery disease: a post-hoc analysis from the LODESTAR randomized clinical trial

BackgroundThe impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial.MethodsIn the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest.ResultsAmong 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007).ConclusionsAmong CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL.Trial registrationClinicalTrials.gov, Identifier: NCT02579499.Graphical abstract

The Impact of Statin Treatment Duration on the Risk of New-Onset Diabetes Mellitus and Recurrent Vascular Events in Ischemic Stroke Patients: A Linked Data Analysis

Introduction: Although statin therapy reduces cardiovascular events, statin use is associated with the risk of new-onset diabetes mellitus (NODM). Using a linked dataset, we evaluated the effect of statin treatment on vascular outcomes and NODM development in patients with ischemic stroke. Methods: From the dataset, we identified 20,250 patients with acute ischemic stroke who had neither a prior history of DM nor a previous history of statin use before the index stroke. Patients were divided into statin users and non-users. The outcomes were NODM and vascular outcomes, including recurrent ischemic stroke and acute myocardial infarction (AMI). Results: Of the 20,250 patients, 13,706 (67.7%) received statin treatment after the index stroke. For the risk of NODM, a time-response relationship was observed between the use of statins and NODM; a longer post-stroke follow-up duration substantially increased the risk of NODM. Among those with ischemic strokes exceeding 3 years, statin users had an approximately 1.7-fold greater risk of NODM than statin non-users. Statin therapy significantly reduced the risk of recurrent ischemic stroke by 54% (HR 0.46, 95% CI, 0.43–0.50, p Conclusion: Statin therapy following ischemic stroke increased the occurrence of NODM in patients over a period of 3 years. Despite the increased risk of NODM, statin therapy shows a beneficial effect in reducing major cardiovascular events such as recurrent ischemic stroke and AMI in patients with ischemic stroke.

Comparative analysis of hemodialysis and peritoneal dialysis on the risk of new onset diabetes mellitus

BackgroundDiabetes mellitus is a significant risk factor for cardiovascular events and mortality in dialysis patients. The impact of different dialysis modalities on the risk of new onset diabetes mellitus (NODM) remains a subject of debate. Previous studies did not adequately account for critical confounding factors such as pre-dialysis glycemic status, medication use, and nutritional status, which may influence the association between dialysis modality and NODM risk. MethodsWe conducted a retrospective cohort study of 1426 non-diabetic end-stage renal disease (ESRD) patients who underwent either hemodialysis (HD) or peritoneal dialysis (PD) at a single medical center. We used different statistical methods, adjusting for potential confounding factors, and accounted for competing risk of death. ResultsOver 12 years, 331 patients (23 %) developed NODM. After adjusting for potential confounding factors and mortality, PD patients had a significantly higher risk of NODM compared to HD patients (adjusted HR 1.52, p = 0.001). A propensity-matched cohort sensitivity analysis yielded similar results. Among patients with prediabetes, those receiving PD had a 2.93 times higher risk of developing NODM than those receiving HD (p for interaction <0.001), whereas no significant difference was observed among euglycemic patients. NODM was also associated with a 1.78 times increased risk of major cardiovascular events. ConclusionOur study provides evidence that PD treatment may increase the risk of NODM in ESRD patients, particularly among those with preexisting prediabetes. These findings highlight the importance of personalized treatment approaches, and nephrologists should consider prediabetes when choosing the dialysis modality for their patients.

Comparative observational study between Atorvastatin and Rosuvastatin based on HbA1c levels of patients diagnosed with acute coronary syndrome and heart failure

Background: Our study aims to compare HbA1c levels in hospitalized acute coronary syndrome and heart failure patients treated with atorvastatin versus rosuvastatin Methods: This is a retrospective, prospective observational study in which the study population includes ACS and HF Hospitalized patients, the study subjects are divided based on patients prescribed with Atorvastatin and Rosuvastatin based on the medication chart, and those patients' previous history of statin use is collected from history chart, patient case notes, doctors notes, laboratory data is collected and documented in data collection form, lab data includes HbA1c, finally compared Atorvastatin and Rosuvastatin using excel and JASP descriptive analysis. Results: Overall, we collected data for 132 cases, of which 55% are males and 45% females, 59.10% are above 61 years of age, 39.39% are diagnosed with ACS and 23.48% are diagnosed with HF, among 67 patients who are using Atorvastatin, there was a significant mean decrease in HbA1c% from 8.359% to 7.901%, and among 65 Rosuvastatin users there was an increase in mean HbA1c% from 8.386% to 8.389%. Additionally for non-diabetic individuals, there was an increase in Hba1c% from 6.339% to 6.387%. Conclusions: We concluded that Atorvastatin is a more effective statin than Rosuvastatin which will reduce the risk of new-onset Diabetes Mellitus in non- diabetic individuals and reduce the risk of increasing complications of diabetes mellitus in patients who are Diabetic.

A novel clinical model for risk prediction and stratification of new-onset diabetes mellitus after distal pancreatectomy.

The incidence of new-onset diabetes mellitus (NODM) after distal pancreatectomy (DP) remains high. Few studies have focused on NODM in patients with pancreatic benign or low-grade malignant lesions (PBLML). This study aimed to develop and validate an effective clinical model for risk prediction and stratification of NODM after DP in patients with PBLML. A follow-up survey was conducted to investigate NODM in patients without preoperative DM who underwent DP. Four hundred and forty-eight patients from Peking Union Medical College Hospital (PUMCH) and 178 from Guangdong Provincial People's Hospital (GDPH) met the inclusion criteria. They constituted the training cohort and the validation cohort, respectively. Univariate and multivariate Cox regression, as well as least absolute shrinkage and selection operator (LASSO) analyses, were used to identify the independent risk factors. The nomogram was constructed and verified. Concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA) were applied to assess its predictive performance and clinical utility. Accordingly, the optimal cut-off point was determined by maximally selected rank statistics method, and the cumulative risk curves for the high- and low-risk populations were plotted to evaluate the discrimination ability of the nomogram. The median follow-up duration was 42.8 months in the PUMCH cohort and 42.9 months in the GDPH cohort. The postoperative cumulative 5-year incidences of DM were 29.1% and 22.1%, respectively. Age, body mass index (BMI), length of pancreatic resection, intraoperative blood loss, and concomitant splenectomy were significant risk factors. The nomogram demonstrated significant predictive utility for post-pancreatectomy DM. The C-indexes of the nomogram were 0.739 and 0.719 in the training and validation cohorts, respectively. ROC curves demonstrated the predictive accuracy of the nomogram, and the calibration curves revealed that prediction results were in general agreement with the actual results. The considerable clinical applicability of the nomogram was certified by DCA. The optimal cut-off point for risk prediction value was 2.88, and the cumulative risk curves of each cohort showed significant differences between the high- and low-risk groups. The nomogram could predict and identify the NODM risk population, and provide guidance to physicians in monitoring and controlling blood glucose levels in PBLML patients after DP.

COVID-19 Vaccination Prior to SARS-CoV-2 Infection Reduced Risk of Subsequent Diabetes Mellitus: A Real-World Investigation Using U.S. Electronic Health Records.

Previous studies have indicated a bidirectional correlation between diabetes and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, no investigation has comprehensively explored the potential of coronavirus disease 2019 (COVID-19) vaccination to reduce the risk of new-onset diabetes in infected individuals. In the first of 2 cohorts, we compared the risk of new-onset diabetes between individuals infected with SARS-CoV-2 and noninfected individuals (N = 1,562,606) using the TriNetX database to validate findings in prior literature. For the second cohort, we identified 83,829 vaccinated and 83,829 unvaccinated COVID-19 survivors from the same period. Diabetes, antihyperglycemic drug use, and a composite of both were defined as outcomes. We conducted Cox proportional hazard regression analysis for the estimation of hazard ratios (HRs) and 95% CIs. Kaplan-Meier analysis was conducted to calculate the incidence of new-onset diabetes. Subgroup analyses based on age (18-44, 45-64, ≥65 years), sex (female, male), race (White, Black or African American, Asian), and BMI categories (<19.9, 20-29, 30-39, ≥40), sensitivities analyses, and a dose-response analysis were conducted to validate the findings. The initial cohort of patients infected with SARS-CoV-2 had a 65% increased risk (HR 1.65; 95% CI 1.62-1.68) of developing new-onset diabetes relative to noninfected individuals. In the second cohort, we observed that vaccinated patients had a 21% lower risk of developing new-onset diabetes in comparison with unvaccinated COVID-19 survivors (HR 0.79; 95% CI 0.73-0.86). Subgroup analyses by sex, age, race, and BMI yielded similar results. These findings were consistent in sensitivity analyses and cross-validation with an independent data set from TriNetX. In conclusion, this study validates a 65% higher risk of new-onset diabetes in SARS-CoV-2-infected individuals compared to noninfected counterparts. Furthermore, COVID-19 survivors who received COVID-19 vaccinations experienced a reduced risk of new-onset diabetes, with a dose-dependent effect. Notably, the protective impact of COVID-19 vaccination is more pronounced among the Black/African American population than other ethnic groups. These findings emphasize the imperative of widespread vaccination to mitigate diabetes risk and the need for tailored strategies for diverse demographic groups to ensure equitable protection.

Differential effects of OATP2B1 on statin accumulation and toxicity in a beta cell model

An increased risk of new-onset diabetes mellitus has been recently reported for statin therapy, and experimental studies have shown reduced glucose-stimulated insulin secretion (GSIS) and mitochondrial dysfunction in beta cells with effects differing among agents. Organic anion transporting polypeptide (OATP) 2B1 contributes to hepatic uptake of rosuvastatin, atorvastatin and pravastatin, three known substrates. Since OATP2B1 is present in beta cells of the human pancreas, we investigated if OATP2B1 facilitates the local accumulation of statins in a rat beta cell model INS-1 832/13 (INS-1) thereby amplifying statin-induced toxicity. OATP2B1 overexpression in INS-1 cells via adenoviral transduction showed 2.5-, 1.8- and 1.4-fold higher cellular retention of rosuvastatin, atorvastatin and pravastatin, respectively, relative to LacZ control, while absolute intracellular concentration was about twice as high for the lipophilic atorvastatin compared to the more hydrophilic rosuvastatin and pravastatin. After 24 h statin treatment at high concentrations, OATP2B1 enhanced statin toxicity involving activation of intrinsic apoptosis (caspase 3/7 activation) and mitochondrial dysfunction (NADH dehydrogenase activity) following rosuvastatin and atorvastatin, which was partly reversed by isoprenoids. OATP2B1 had no effect on statin-induced reduction in GSIS, mitochondrial electron transport chain complex expression or caspase 9 activation. We confirmed a dose-dependent reduction in insulin secretion by rosuvastatin and atorvastatin in native INS-1 with a modest change in cellular ATP. Collectively, our results indicate a role of OATP2B1, which is abundant in human beta cells, in statin accumulation and statin-induced toxicity but not insulin secretion of rosuvastatin and atorvastatin in INS-1 cells.

Prevalence and risk of new-onset diabetes mellitus after COVID-19: a systematic review and meta-analysis.

After the acute phase of SARS-CoV-2 infection, the onset of glycemic impairment and diabetes have been reported. Nevertheless, the exact burden of glycemic impairment and diabetes after COVID-19 has not been clearly described. Electronic search was run in Pubmed (MEDLINE), Web of Science, Scopus, and ClinicalTrial.org for reports published from database inception to September 2022. We included observational studies reporting quantitative data on diabetes prevalence or its onset in subjects with a history of SARS-CoV-2 infection from at least 60 days. Risk of bias was assessed by the JBI's critical appraisal checklist. Random effect model was used to calculate pooled data. The review protocol was registered on PROSPERO (CRD42022310722). Among 1,630 records screened, 20 studies were included in the analysis. The mean or median age of participants ranged from ~ 35 to 64 years, with a percentage of males ranging from 28% to 80%. Only two studies were considered at low risk of bias. The estimate of diabetes prevalence, calculated on a total of 320,948 participants pooled with 38,731 cases, was 16% (95%CI: 11-22%). The estimate of proportion of incident cases of diabetes was 1.6% (95%CI: 0.8-2.7%). Subgroup analysis showed that previous hospitalization increased the prevalence of diabetes and the proportion of incident cases. Diabetes is common in individuals who have experienced SARS-CoV-2 infection, especially if they required hospitalization. This data may be helpful to screen for diabetes and manage its complications in individuals who experienced COVID-19. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022310722, identifier CRD42022310722.

Racial disparities in new-onset diabetes mellitus in prostate cancer patients on androgen deprivation therapy: a retrospective analysis of TriNetX data.

Prostate cancer (PCa) is the most common cancer in men in the US and androgen deprivation therapy (ADT) is the most frequently used systemic therapy for PCa. Data suggest that ADT is associated with an increased risk of new-onset diabetes mellitus (NODM) and cardiovascular complications. As the incidence and mortality of PCa are highest among the African American (AA) population, it is important to evaluate the difference in the incidence of NODM and ischemic heart disease (IHD) between AA men compared to Caucasian men. This is a retrospective cohort study utilizing the TriNetX database to assess NODM and IHD risk, risk difference, and risk ratio (RR) after recent ADT initiation in an AA cohort and a Caucasian cohort of patients with PCa. Propensity score matching (PSM) was performed by age, BMI, and confounding comorbidities. After matching, the cohort included 1159 AA patients and 843 Caucasian patients with NODM after ADT initiation. The IHD cohort included 1269 AA patients and 1248 Caucasian patients. The risk of incidence of NODM is higher among AA men at 11.6% risk compared to Caucasian men at 7.4%. The risk difference is 4.1% (95% CI = 3.4, 4.9) p = 0.000. The RR is 1.56 (95% CI = 1.43, 1.70). In contrast, risk difference and risk ratio of IHD was not significant between AA and Caucasian groups. ADT exposure increases the risk of NODM in men with PCa, especially among AA men compared with Caucasian men. Men receiving ADT should be monitored routinely for signs and symptoms of metabolic syndrome and diabetes. Targeted close monitoring of AA men on ADT would be critical to prevent and treat metabolic complications with potential of reducing disparities in PCa morbidity.

SGLT2 inhibitors can reduce the incidence of abnormal blood glucose caused by statins in non-diabetes patients with HFrEF after PCI

BackgroundTaking statins for a long time is associated with an increased risk of new-onset diabetes mellitus. Sodium-glucose cotransporter-2 (SGLT2) inhibitors can reduce insulin resistance and improve pancreatic β-cell function.Methods and resultsIn total, 333 non-diabetes patients with heart failure with reduced ejection fraction (HFrEF) after percutaneous coronary intervention (PCI) are included. The enrolled patients are divided into a matched group (n = 198) and an SGLT2 inhibitors group (n = 135). There are no statistical differences in general information between the two groups before treatment. After a mean follow-up time of 13 months, abnormal blood glucose levels are significantly higher in the matched group than in the SGLT2 inhibitors group (6.06 vs. 0.74%, P < 0.05). There are no statistically significant differences in the alanine aminotransferase (ALT), uric acid (UA), and estimated glomerular filtration (eGFR) levels between the two groups.ConclusionSGLT2 inhibitors play a significant protective role in reducing the risk of statins-induced abnormal blood glucose in non-diabetes patients with HFrEF after PCI, without increasing the burden on the heart, kidneys, and liver.

The incidence of cytomegalovirus and BK polyomavirus infections in kidney transplant patients receiving mTOR inhibitors: A systematic review and meta-analysis.

Cytomegalovirus (CMV) and BK polyomavirus (BKPyV) infections after kidney transplant have become increasingly prevalent. Based on previous studies, the mammalian target of rapamycin (mTOR) inhibitors seem like attractive alternatives with antiviral activity. The objective of this systematic review and meta-analysis was to investigate the incidence of CMV and BKPyV infections in kidney transplantation recipients receiving mTOR inhibitors. This meta-analysis included three comparisons of immunosuppressant regimens commonly used after kidney transplantation: Comparison 1: mTOR inhibitors versus calcineurin inhibitors (CNI); Comparison 2: mTOR inhibitors versus antimetabolites (AM); and Comparison 3: mTOR inhibitors plus a reduced-dose of CNI versus AM plus a standard-dose of CNI. The group containing mTOR inhibitors was the study group and the remaining one was the control group. The incidence of CMV or BKPyV infection defined by positive culture, serology, or polymerase chain reaction testing was the primary outcome. A total of 61 studies involving 13,609 patients were included. As compared with the control group, a significantly decreased risk of CMV and BKPyV infections favoring the mTOR inhibitors-based group was shown in comparisons 1, 2, and 3 (p < 0.05). Compared with the control group in all three comparisons, mTOR inhibitors made no difference in regard to death and graft loss (p > 0.05). Compared with CNI, the incidence of biopsy-proven acute rejection (BPAR) and anemia was higher with mTOR inhibitors (p < 0.05). In comparisons 2 and 3, the risk of new-onset diabetes mellitus (NODM) was higher with mTOR inhibitors (p < 0.05). Early introduction of mTOR inhibitors reduced more CMV infections in comparisons 1 and 2 (p < 0.05). The mTOR inhibitor-based regimen is an attractive alternative with lower risk of CMV and BKPyV infections in kidney transplant recipients. The combination regimen is more appropriate and acceptable than the mTOR-inhibitor monotherapy-based regimen. Early introduction of mTOR inhibitors is recommended, although it is worth noting that attention should be paid to wound healing when mTOR inhibitors are introduced early.

Risk of New-Onset Diabetes Mellitus as a Post-COVID-19 Condition and Possible Mechanisms: A Scoping Review.

Long-term effects of COVID-19 are becoming more apparent even as the severity of acute infection is decreasing due to vaccinations and treatment. In this scoping review, we explored the current literature for the relationship between COVID-19 infection and new-onset diabetes mellitus four weeks after acute infection. We systematically searched the peer-reviewed literature published in English between 1 January 2020 and 31 August 2022 to study the risk of new-onset diabetes mellitus post-COVID-19 infection. This scoping review yielded 11 articles based on our inclusion and exclusion criteria. Except for one, all studies suggested an increased risk of new-onset diabetes mellitus 4 weeks after acute infection. This risk appears most in the first six months after the acute COVID-19 infection and seems to increase in a graded fashion based on the severity of the initial COVID-19 infection. Our review suggests a possible association of new-onset diabetes mellitus 4 weeks after acute COVID-19 infection. Since the severity of COVID-19 infection is associated with the development of post-infectious diabetes, vaccination that reduces the severity of acute COVID-19 infection might help to reduce the risk of post-COVID-19 diabetes mellitus. More studies are needed to better understand and quantify the association of post-COVID-19 conditions with diabetes and the role of vaccination in influencing it.

Longitudinal Exposure to Tacrolimus and New-Onset Diabetes Mellitus in Renal Transplant Patients

Tacrolimus is an immunosuppressant widely used in transplantations requiring mandatory concentration-controlled dosing to prevent acute rejection or adverse effects, including new-onset diabetes mellitus (NODM). However, no relationship between NODM and tacrolimus exposure has been established. This study aimed to evaluate the relationship between cumulative tacrolimus exposure and NODM occurrence. A total of 452 kidney transplant patients were included in this study. Sixteen patients developed NODM during the first 3 months after transplant. We considered all tacrolimus concentration (C0) values collected until the diagnosis of NODM in these patients and until 3 months after transplant in the others. New tacrolimus cumulative exposure metrics were derived from the time profile of the tacrolimus morning predose concentration, C0: the percentage of C0 values > cutoff, the average of C0 values above the cutoff, and the percentage of the area under C0 versus time curve, AUCC0, above the cutoff. The cutoff chosen was 15 ng/mL, corresponding to the higher end of the therapeutic range for the early post-transplant period. The influence of these metrics on NODM and other clinical and biological characteristics was investigated using the Cox models. The percentage of C0 > 15 mcg/L was statistically different between patients with and without NODM (P = 0.01). Only these tacrolimus C0-derived metrics were significantly associated with an increased risk of NODM [HR: 1.73 (1.43-2.10, P < 0.001)]. This study shows that tacrolimus concentrations >15 mcg/L affect the incidence of NODM.

Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm?

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are low-density lipoprotein cholesterol (LDL-C)-lowering drugs that play a critical role in lipoprotein clearance and metabolism. PCSK9i are used in patients with familial hypercholesterolemia and for the secondary prevention of acute cardiovascular events in patients with atherosclerotic cardiovascular disease (CVD). Methods: We focused on the literature from 2015, the year of approval of the PCSK9 monoclonal antibodies, to the present on the use of PCSK9i not only in the lipid field but also by evaluating their effects on metabolic factors. Results: PCSK9 inhibits cholesterol efflux from macrophages and contributes to the formation of macrophage foam cells. PCSK9 has the ability to bind to Toll-like receptors, thus mediating the inflammatory response and binding to scavenger receptor B/cluster of differentiation 36. PCSK9i lower the entire spectrum of apolipoprotein B-100 containing lipoproteins (LDL, very LDLs, intermediate-density lipoproteins, and lipoprotein[a]) in high CVD-risk patients. Moreover, PCSK9 inhibitors are neutral on risk for new-onset diabetes mellitus and might have a beneficial impact on the development of nonalcoholic fatty liver disease by improving lipid and inflammatory biomarker profiles, steatosis biomarkers such as the triglyceride-glucose index, and hepatic steatosis index, although there are no comprehensive studies with long-term follow-up studies. Conclusion: The discovery of PCSK9i has opened a new era in therapeutic management in patients with hypercholesterolemia and high cardiovascular risk. Increasingly, there has been mounting scientific and clinical evidence supporting the safety and tolerability of PCSK9i.

Reduction of Cardiovascular Disease and Mortality Versus Risk of New-Onset Diabetes Mellitus With Statin Use in Patients With Rheumatoid Arthritis.

To assess the effect of statin use on the risk of cardiovascular disease (CVD), all-cause mortality, and type 2 diabetes mellitus (DM) in patients with rheumatoid arthritis (RA). We identified a cohort of patients with RA between 1989 and 2018, within the UK Clinical Practice Research Datalink. We employed a prevalent new-user cohort design by which patients initiating statins were each matched to 2 concurrent nonusers by the time-conditional propensity score (TCPS). Patients were followed until the occurrence of the composite end point of myocardial infarction, stroke, hospitalized heart failure or CVD mortality, all-cause mortality, and incident type 2 DM. The Cox proportional hazards model was used to estimate the hazard ratio (HR) of each outcome associated with as-treated statin use, with adjustment for TCPS deciles and imbalanced covariables. Among 1,768 statin initiators and 3,528 nonusers, 63 versus 340 CVD (3.0 per 100 person-years versus 2.7 per 100 person-years) and 62 versus 525 deaths (2.8 per 100 person-years versus 4.1 per 100 person-years) occurred. Incident type 2 DM was noted in 128 of 3,608 statin initiators (3.0 per 100 person-years) and 518 of 7,208 nonusers (2.0 per 100 person-years). Statin initiation was associated with 32% (HR 0.68 [95% confidence interval (95% CI) 0.51-0.90]) reduction in CVD, 54% (HR 0.46 [95% CI 0.35-0.60]) reduction in all-cause mortality, and 33% increase in type 2 DM (HR 1.33 [95% CI 1.09-1.63]). The number needed to treat/number needed to harm to prevent a CVD or all-cause mortality or to cause type 2 DM in 1 year was 102, 42, and 127, respectively. Statins are associated with important reductions in CVD and mortality that outweigh the modest increase in type 2 DM risk in RA patients.

Comparative effects of rosuvastatin and atorvastatin on the risk of new-onset diabetes mellitus in patients with acute coronary syndrome receiving percutaneous coronary intervention: a retrospective cohort study

Abstract Background Statins are frequently prescribed to reduce cardiovascular morbidity and mortality by lowering low-density lipoprotein cholesterol levels. However, the use of statins leads to an increased incidence of new-onset type 2 diabetes mellitus (NODM). Our study aims to compare the effect of rosuvastatin versus atorvastatin on NODM in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) within 18 months of follow-up. Methods A retrospective cohort study was conducted on patients with ACS who underwent PCI and were treated with rosuvastatin or atorvastatin between June 2012 and June 2017. The survival functions between the 2 groups were estimated using the Kaplan-Meier method and compared using the log-rank test with NODM as the endpoint. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk factors of NODM. Results In total, 220 patients received rosuvastatin and 168 atorvastatin. The cumulative incidence of NODM in the rosuvastatin group was lower but did not reach statistical significance, compared with that in the atorvastatin group (7.27% vs. 12.50%, respectively; log-rank P = 0.08). Using Cox proportional hazards models, baseline fasting blood glucose level was associated with a statistically significant increase in the risk of NODM (HR: 4.56; 95% CI: 2.83–7.36; P &lt; 0.01). Conclusion Long-term use of moderate rosuvastatin had a similar incidence of NODM compared with atorvastatin in patients with ACS receiving PCI.

Impact of pitavastatin on new-onset diabetes mellitus compared to atorvastatin and rosuvastatin: a distributed network analysis of 10 real-world databases

BackgroundStatin treatment increases the risk of new-onset diabetes mellitus (NODM); however, data directly comparing the risk of NODM among individual statins is limited. We compared the risk of NODM between patients using pitavastatin and atorvastatin or rosuvastatin using reliable, large-scale data.MethodsData of electronic health records from ten hospitals converted to the Observational Medical Outcomes Partnership Common Data Model (n = 14,605,368 patients) were used to identify new users of pitavastatin, atorvastatin, or rosuvastatin (atorvastatin + rosuvastatin) for ≥ 180 days without a previous history of diabetes or HbA1c level ≥ 5.7%. We conducted a cohort study using Cox regression analysis to examine the hazard ratio (HR) of NODM after propensity score matching (PSM) and then performed an aggregate meta-analysis of the HR.ResultsAfter 1:2 PSM, 10,238 new pitavastatin users (15,998 person-years of follow-up) and 18,605 atorvastatin + rosuvastatin users (33,477 person-years of follow-up) were pooled from 10 databases. The meta-analysis of the HRs demonstrated that pitavastatin resulted in a significantly reduced risk of NODM than atorvastatin + rosuvastatin (HR 0.72; 95% CI 0.59–0.87). In sub-analysis, pitavastatin was associated with a lower risk of NODM than atorvastatin or rosuvastatin after 1:1 PSM (HR 0.69; CI 0.54–0.88 and HR 0.74; CI 0.55–0.99, respectively). A consistently low risk of NODM in pitavastatin users was observed when compared with low-to-moderate-intensity atorvastatin + rosuvastatin users (HR 0.78; CI 0.62–0.98).ConclusionsIn this retrospective, multicenter active-comparator, new-user, cohort study, pitavastatin reduced the risk of NODM compared with atorvastatin or rosuvastatin.

Safety of proprotein convertase subtilisin/kexin 9 inhibitors: a systematic review and meta-analysis

ObjectiveTo determine the harms of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in people who need lipid-lowering therapy.MethodsThis systematic review included randomised controlled trials that compared PCSK9 inhibitors with placebo, standard...

Risk of New-Onset Diabetes Mellitus Associated with Antirheumatic Drugs in Patients with Rheumatoid Arthritis: A Nationwide Population Study.

Background: This study aimed to investigate the effect of disease-modifying antirheumatic drugs (DMARDs) on diabetes mellitus (DM) development in rheumatoid arthritis (RA). Methods: This nested case–control study with a cohort of 69,779 DM-naïve adult patients with RA was conducted from 2011 to 2019 in South Korea. Cases with incident DM were identified and individually matched to randomly selected controls (1:4). DMARDs use was measured for 1 year before the index date and stratified by exposure duration. The association of each DMARD use with DM risk was estimated using conditional logistic regression adjusted for comorbidities and concomitant drug use. Results: Of the patients, 5.4% were newly diagnosed with DM. The use of statins and a higher cumulative dose of corticosteroids were associated with an increased DM risk. In a multivariable-adjusted analysis, cumulative duration of exposure (CDE) >270 days/year, hydroxychloroquine (HCQ; adjusted odds ratio [aOR], 0.76) and methotrexate (MTX; aOR, 0.81) were associated with a significant decrease in DM risk, and tacrolimus (TAC; aOR, 1.27) was associated with an increased risk. Conclusions: Long-term use of HCQ and MTX (>270 days/year) was associated with a reduction in DM incidence as opposed to TAC.