Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control

Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality and complications in patients with diabetes mellitus. Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19. Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors (DPP-4i) in diabetic patients with COVID-19. DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes, namely viral entry inhibition, anti-inflammatory and anti-fibrotic effects and glycemic control. This has raised the pro-mising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes. This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.     

A Comparison of the Cost-Effectiveness of Lifestyle Interventions in Pregnancy

ObjectivesLifestyle interventions during pregnancy improve maternal and infant outcomes. We aimed to compare the cost-effectiveness of 4 antenatal lifestyle intervention types with standard care.MethodsA decision tree model was constructed to compare lifestyle intervention effects from a novel meta-analysis. The target population was women with singleton pregnancies and births at more than 20 weeks’ gestation. Interventions were categorized as diet, diet with physical activity, physical activity, and mixed (lacking structured diet and, or, physical activity components). The outcome of interest was cost per case prevented (gestational diabetes, hypertensive disorders in pregnancy, cesarean birth) expressed as an incremental cost-effectiveness ratio (ICER) from the Australian public healthcare perspective. Scenario analyses were included for all structured interventions combined and by adding neonatal intensive care unit costs. Costs were estimated from published data and consultations with experts and updated to 2019 values. Discounting was not applied owing to the short time horizon.ResultsPhysical activity interventions reduced adverse maternal events by 4.2% in the intervention group compared with standard care and could be cost saving. Diet and diet with physical activity interventions reduced events by 3.5% (ICER = A$4882) and 2.9% (ICER = A$2020), respectively. Mixed interventions did not reduce events and were dominated by standard care. In scenario analysis, all structured interventions combined and all interventions when including neonatal intensive care unit costs (except mixed) may be cost saving. Probabilistic sensitivity analysis showed that for physical activity and all structured interventions combined, the probability of being cost saving was 58% and 41%, respectively.ConclusionsGovernments can expect a good return on investment and cost savings when implementing effective lifestyle interventions population-wide.     

Economic Evaluation of Prenatal and Postpartum Care in Women With Gestational Diabetes and Hypertensive Disorders of Pregnancy: A Systematic Review

ObjectivesThis study aimed to summarize evidence on the economic outcomes of prenatal and postpartum interventions for the management of gestational diabetes mellitus and hypertensive disorders of pregnancy (HDP), assess the quality of each study, and identify research gaps that may inform future research.MethodsElectronic databases including PubMed/MEDLINE, Embase, the Cochrane Library, and Cochrane Central Register of Controlled Trials were searched from January 1, 2000, to October 1, 2021. Selected studies were included in narrative synthesis and extracted data were presented in narrative and tabular forms. The quality of each study was assessed using the Consolidated Health Economic Evaluation Reporting Standards and Consensus on Health Economic Criteria list.ResultsAmong the 22 studies identified through the systematic review, 19 reported favorable cost-effectiveness of the intervention. For prenatal management of HDP, home blood pressure monitoring was found to be cost-effective compared with in-person visits in improving maternal and neonatal outcomes. For postpartum care, regular screening for hypertension or metabolic syndrome followed by subsequent treatment was found to be cost-effective compared with no screening in women with a history of gestational diabetes mellitus or HDP.ConclusionsExisting economic evaluation studies showed that prenatal home blood pressure monitoring and postpartum screening for hypertension or metabolic syndrome were cost-effective. Nevertheless, limitations in the approach of the current economic evaluations may dampen the quality of the evidence and warrant further investigation.     

Sudden Cardiac Death in Patients With Type 1 Versus Type 2 Diabetes

ObjectiveTo investigate the association between type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) with risk of sudden cardiac arrest (SCA).MethodsIn a prospective community-based study of SCA from February 1, 2002, through November 30, 2019, we ascertained 2771 cases age 18 years of age or older and matched them to 8313 controls based on geography, age, sex, and race/ethnicity. We used logistic regression to evaluate the independent association between diabetes, T1D, T2D, and SCA.ResultsPatients had a mean age of 64.5±15.9 years, were 33.3% female and 23.9% non-White race. Overall, 36.7% (n=1016) of cases and 23.8% (n=1981) of controls had diabetes. Among individuals with diabetes, the proportion of T1D was 6.5% (n=66) among cases and 2.0% among controls (n=40). Diabetes was associated with 1.5-times higher odds of SCA. Compared with those without diabetes, the odds ratio and 95% CI for SCA was 4.36 (95% CI, 2.81 to 6.75; P<.001) in T1D and 1.45 (95% CI, 1.30 to 1.63; P<.001) in T2D after multivariable adjustment. Among those with diabetes, the odds of having SCA were 2.41 times higher in T1D than in T2D (95% CI, 1.53 to 3.80; P<.001). Cases of SCA with T1D were more likely to have an unwitnessed arrest, less likely to receive resuscitation, and less likely to survive compared with those with T2D.ConclusionType 1 diabetes was more strongly associated with SCA compared with T2D and had less favorable outcomes following resuscitation. Diabetes type could influence the approach to risk stratification and prevention of SCA.     

Trends of self-reported non-adherence among type 2 diabetes medication users in the United States across three years using the self-reported Medication Adherence Reasons Scale

Background & aimsTo determine the trends of self-reported non-adherence rates among adults taking Type 2 medicines (T2D) medicines between 2017 and 2019 and to identify the patterns for the frequently reported reasons for non-adherence in the United States.Methods & resultsData from the National Health and Wellness Survey, a self-administered, internet-based cross-sectional survey of US adults from 2017 to 2019 was used. Non-adherence was measured using the self-reported Medication Adherence Reasons Scale (MAR-Scale). Frequencies were used to identify the reasons for non-adherence for insulin and non-insulin therapies for T2D.Data were obtained from 2983 respondents in 2017, 5416 in 2018, and 5268 in 2019. Based on the MAR-Scale, the self-reported medication non-adherence rate was 25% in 2017, 21% in 2018, and 27% in 2019. The most common reason for non-adherence across all the three years was simple forgetfulness, yet patients reported the lowest mean number of days missing medication for that reason. Though less frequently reported, non-adherence lasted longer when patient did not know how to take their medicines, cost was a reason, or had concerns about the long term effects of the medicines.ConclusionsWith no significant improvement in adherence with T2D medicines over time, regardless of better awareness and extensive diabetes education, focus should be on individualized non-adherence reasons-based interventions.     

Genome-wide gene and serum ferritin interaction in the development of type 2 diabetes in adults aged 40 years or older

Background and aimsElevated serum ferritin is associated with incident Type 2 diabetes (T2D), but the interactions between serum ferritin and genetic factors which may improve understanding underlying mechanism in the development of T2D are still unclear. We determined the gene–ferritin interactions on the development of T2D by genome-wide gene–ferritin interaction analyses.Methods and resultsA total of 3405 participants from two prospective cohorts of community living residents were included, and the median follow-time was 3.99 years. Genome-wide gene–ferritin interactions were analyzed using the joint test with two degrees of freedom and the interaction test with one degree of freedom. There were 18 SNPs selected in the joint test. Finally, four independent variants [rs355140 (LINC00312), rs4075576 (nearby PDGFA), rs1332202 (PTPRD), and rs713157 (nearby LINC00900)] with low pairwise linkage disequilibrium (r2 < 0.2) and located at least 1000 kb from the index SNP showed interactions with serum ferritin level. In the association analyses between serum ferritin levels (tertiles of ferritin and ferritin status) and the incidence of T2D according to genotype, the Incidence Rate Ratios (IRRs) in the highest tertile of ferritin level (vs. the lowest tertile) were greater for participants with heterozygotes of risk alleles of each of the four SNP than IRRs for those with wild type. Compared with the normal group, the elevated ferritin group also had a higher risk of T2D for all genetic variants of risk alleles, particularly its homozygotes.ConclusionSerum ferritin level interacts with genetic variants (rs355140, rs4075576, rs1332202, and rs713157) in the development of T2D.     

Outcomes of coronary artery bypass grafting in patients with heart failure with a midrange ejection fraction

BackgroundCoronary artery bypass grafting (CABG) improves survival in patients with heart failure and severely reduced left ventricular systolic function (LVEF). Limited data exist regarding adverse cardiovascular event rates after CABG in patients with heart failure with midrange ejection fraction (HFmrEF; LVEF > 40% and < 55%).MethodsWe analyzed data on isolated CABG patients from the Veterans Affairs national database (2010-2019). We stratified patients into control (normal LVEF and no heart failure), HFmrEF, and heart failure with reduced LVEF (HFrEF) groups. We compared all-cause mortality and heart failure hospitalization rates between groups with a Cox model and recurrent events analysis, respectively.ResultsIn 6533 veterans, HFmrEF and HFrEF was present in 1715 (26.3%) and 566 (8.6%) respectively; the control group had 4252 (65.1%) patients. HFrEF patients were more likely to have diabetes mellitus (59%), insulin therapy (36%), and previous myocardial infarction (31%). Anemia was more prevalent in patients with HFrEF (49%) as was a lower serum albumin (mean, 3.6 mg/dL). Compared with the control group, a higher risk of death was observed in the HFmrEF (hazard ratio [HR], 1.3 [1.2-1.5)] and HFrEF (HR, 1.5 [1.2-1.7]) groups. HFmrEF patients had the higher risk of myocardial infarction (subdistribution HR, 1.2 [1-1.6]; P = .04). Risk of heart failure hospitalization was higher in patients with HFmrEF (HR, 4.1 [3.5-4.7]) and patients with HFrEF (HR, 7.2 [6.2-8.5]).ConclusionsHeart failure with midrange ejection fraction negatively affects survival after CABG. These patients also experience higher rates myocardial infarction and heart failure hospitalization.