Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The latter is a pandemic that has the potential of developing into a severe illness manifesting as systemic inflammatory response syndrome, acute respiratory distress syndrome, multi-organ involvement and shock. In addition, advanced age and male sex and certain underlying health conditions, like type 2 diabetes mellitus (T2DM), predispose to a higher risk of greater COVID-19 severity and mortality. This calls for an urgent identification of antidiabetic agents associated with more favourable COVID-19 outcomes among patients with T2DM, as well as recognition of their potential underlying mechanisms. It is crucial that individuals with T2DM be kept under very stringent glycaemic control in order to avoid developing various cardiovascular, renal and metabolic complications associated with more severe forms of COVID-19 that lead to increased mortality. The use of novel antidiabetic agents dipeptidyl peptidase 4 inhibitors (DPP4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) in subjects with T2DM may have beneficial effects on COVID-19 outcomes. However, relevant studies either show inconsistent results (DPP4i) or are still too few (SGLT2i and GLP-1RAs). Further research is therefore needed to assess the impact of these agents on COVID-19 outcomes.
Project description:AimsThis study aimed to assess the impact of different antidiabetic agents on individuals with diabetes and COVID-19.MethodsWe searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to October 31, 2021 and included seven antidiabetic agents. The data were pooled via traditional pairwise meta-analysis and Bayesian network meta-analysis.ResultsThe pairwise meta-analysis included 35 studies. Metformin (odds ratio (OR), 0.74; P=0.001), dipeptidyl peptidase-4 inhibitors (DPP4i) (OR, 0.88; P=0.04), sodium-glucose cotransporter-2 inhibitors (SGLT2i) (OR, 0.82; P=0.001), and glucagon-like peptide-1 receptor agonists (GLP1RA) (OR, 0.91; P=0.02) treatment were associated with lower COVID-19 mortality in individuals with diabetes compared to respective non-users. However, insulin treatment resulted in higher mortality (OR, 1.8; P=0.001). Mortality did not significantly differ in sulfonylurea (OR, 0.97; P=0.56) and thiazolidinediones (TZDs) (OR, 1.00; P=0.96) users. Furthermore, due to limited data, we analyzed five antidiabetic agents (metformin, DPP4i, sulfonylurea, insulin, and SGLT2i) and found no association between them and severe disease risk (all P>0.05). The Bayesian network meta-analysis included 18 studies. GLP1RA and SGLT2i had the highest first and second rank probability (67.3% and 62.5%, respectively). Insulin showed the maximum probability of ranking seventh (97.0%). Metformin had the third and fourth highest rank probability of 44.8% and 38.9%, respectively. Meanwhile, DPP4i had the fifth-highest rank probability of 42.4%, followed by sulfonylurea at 45.1%.ConclusionMetformin, DPP4i, SGLT2i, and GLP1RA treatments were highly possible to reduced COVID-19 mortality risk in individuals with diabetes, while insulin might be related to increased mortality risk. Sulfonylurea and TZDs treatments were not associated with mortality. None of the antidiabetic agents studied were associated with the risk of severe disease. Additionally, GLP1RA probably had the most significant protective effect against death, followed by SGLT2i and metformin.Systematic review registrationPROSPERO (CRD42021288200).
Project description:BackgroundThe coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) are at high risk of fatal outcomes. This meta-analysis quantifies the prevalence of mortality among (1) diabetic and (2) non-diabetic, and (3) the prevalence of DM, in hospitalized COVID-19 patients.MethodsPublished studies were retrieved from four electronic databases (PubMed, Embase, Scopus, and medRxiv) and appraised critically utilizing the National Heart, Lung, and Blood Institute's tool. Meta-analyses were performed using the random-effects model. The measures of heterogeneity were ascertained by I- squared (I 2 ) and Chi-squared (Chi 2 ) tests statistics. Predictors of heterogeneity were quantified using meta-regression models.ResultsOf the reviewed 475 publications, 22 studies (chiefly case series (59.09 %)), sourcing data of 45,775 hospitalized COVID-19 patients, were deemed eligible. The weighted prevalence of mortality in hospitlized COVID-19 patients with DM (20.0 %, 95 % CI: 15.0-26.0; I 2 , 96.8 %) was 82 % (1.82-time) higher than that in non-DM patients (11.0 %, 95 % CI: 5.0-16.0; I 2 , 99.3 %). The prevalence of mortality among DM patients was highest in Europe (28.0 %; 95 % CI: 14.0-44.0) followed by the United States (20.0 %, 95 % CI: 11.0-32.0) and Asia (17.0 %, 95 % CI: 8.0-28.0). Sample size and severity of the COVID-19 were associated (p < 0.05) with variability in the prevalence of mortality. The weighted prevalence of DM among hospitalized COVID-19 patients was 20 % (95 % confidence interval [CI]: 15-25, I 2 , 99.3 %). Overall, the quality of the studies was fair.ConclusionsHospitalized COVID-19 patients were appreciably burdened with a high prevalence of DM. DM contributed to the increased risk of mortality among hospitalized COVID-19 patients compared to non-DM patients, particularly among critically ill patients. Registration: PROSPERO (registration no. CRD42020196589).Supplementary informationThe online version contains supplementary material available at 10.1007/s40200-021-00779-2.
Project description:Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk-factor for severe disease. Inflammation is central to the aetiology of both conditions where immune responses influence disease course. Identifying at-risk groups through immuno-inflammatory signatures can direct personalised care and help develop potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leukocyte populations in circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia, of CD8+ lymphocytes, was associated with severe COVID-19 and intensive care admission in non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia of classical monocytes were specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Over-expression of inflammatory markers reminiscent of the type-1 interferon pathway underlaid the immunophenotype associated with T2D. These changes may contribute to severity of COVID-19 in T2D. These findings show characteristics of severe COVID-19 in T2D as well as provide evidence that type-1 interferons may be actionable targets for future studies.
Project description:The presence of SARS-CoV-2 was officially documented in Europe at the end of February 2020. Despite many observations, the real impact of COVID-19 in the European Union (EU), its underlying factors and their contribution to mortality and morbidity outcomes were never systematically investigated. The aim of the present work is to provide an overview and a meta-analysis of main predictors and of country differences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-associated mortality rate (MR) in hospitalized patients. Out of 3714 retrieved articles, 87 studies were considered, including 35,486 patients (mean age 60.9?±?8.2 years) and 5867 deaths. After adjustment for confounders, diabetes mellitus was the best predictors of MR in an age- and sex-dependent manner, followed by chronic pulmonary obstructive diseases and malignancies. In both the US and Europe, MR was higher than that reported in Asia (25[20;29] % and 20[17;23] % vs. 13[10;17]%; both p?<?0.02). Among clinical parameters, dyspnea, fatigue and myalgia, along with respiratory rate, emerged as the best predictors of MR. Finally, reduced lymphocyte and platelet count, along with increased D-dimer levels, all significantly contributed to increased mortality. The optimization of glucose profile along with an adequate thrombotic complications preventive strategy must become routine practice in diseased SARS-CoV-2 infected patients.
Project description:Alterations in cardiac biomarkers have been reported in patients with coronavirus disease 2019 (COVID-19) in relation to disease severity and mortality. We conducted a systematic review and meta-analysis with meta-regression of studies reporting B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) plasma concentrations in COVID-19. We searched PubMed, Web of Science, and Scopus, between January 2020 and 2021, for studies reporting BNP/NT-proBNP concentrations, measures of COVID-19 severity, and survival status (PROSPERO registration number: CRD42021239190). Forty-four studies in 18,856 COVID-19 patients were included in the meta-analysis and meta-regression. In pooled results, BNP/NT-proBNP concentrations were significantly higher in patients with high severity or non-survivor status when compared to patients with low severity or survivor status during follow up (SMD = 1.07, 95% CI: 0.89-1.24, and p < 0.001). We observed extreme between-study heterogeneity (I 2 = 93.9%, p < 0.001). In sensitivity analysis, the magnitude and the direction of the effect size were not substantially modified after sequentially removing individual studies and re-assessing the pooled estimates, (effect size range, 0.99 - 1.10). No publication bias was observed with the Begg's (p = 0.26) and Egger's (p = 0.40) t-tests. In meta-regression analysis, the SMD was significantly and positively associated with D-dimer (t = 2.22, p = 0.03), myoglobin (t = 2.40, p = 0.04), LDH (t = 2.38, p = 0.02), and procalcitonin (t = 2.56, p = 0.01) concentrations. Therefore, higher BNP/NT-proBNP plasma concentrations were significantly associated with severe disease and mortality in COVID-19 patients.
Project description:OBJECTIVE: Previous reviews of the effect of oral antidiabetic (OAD) agents on A1C levels summarized studies with varying designs and methodological approaches. Using predetermined methodological criteria, we evaluated the effect of OAD agents on A1C levels. RESEARCH DESIGN AND METHODS: The Excerpta Medica (EMBASE), the Medical Literature Analysis and Retrieval System Online (MEDLINE), and the Cochrane Central Register of Controlled Trials databases were searched from 1980 through May 2008. Reference lists from systematic reviews, meta-analyses, and clinical practice guidelines were also reviewed. Two evaluators independently selected and reviewed eligible studies. RESULTS: A total of 61 trials reporting 103 comparisons met the selection criteria, which included 26,367 study participants, 15,760 randomized to an intervention drug(s), and 10,607 randomized to placebo. Most OAD agents lowered A1C levels by 0.5-1.25%, whereas thiazolidinediones and sulfonylureas lowered A1C levels by approximately 1.0-1.25%. By meta-regression, a 1% higher baseline A1C level predicted a 0.5 (95% CI 0.1-0.9) greater reduction in A1C levels after 6 months of OAD agent therapy. No clear effect of diabetes duration on the change in A1C with therapy was noted. CONCLUSIONS: The benefit of initiating an OAD agent is most apparent within the first 4 to 6 months, with A1C levels unlikely to fall more than 1.5% on average. Pretreated A1C levels have a modest effect on the fall of A1C levels in response to treatment.
Project description:Background and aimsThis systematic review and meta-analysis aimed to evaluate the current evidence available to investigate clinical outcomes between patients with type 1 and type 2 diabetes.MethodsMEDLINE (Pubmed), Scopus, Web of Science, Cochrane library, Google scholar and Clinicaltrials.gov were searched. Randomized controlled trials (RCTs), non-randomized trials, and observational studies were eligible for inclusion. National Institutes of Health Quality Assessment Tool was used to assess the quality. Data were pooled by the Restricted-maximum-likelihood random-effects approach.ResultsTotal 11 studies comprising 7690415 individuals were included in this study. The log OR for the pooled data for all-cause mortality rate was -0.71 (95% CI: -1.38 to -0.03). Based on the pooled results, type 1 diabetic COVID-19 patients may have a better prognosis for mortality. There were no significant differences between groups in term of ICU-admission log OR -0.22 (95% CI: -0.81 to 0.37), and hospitalization log OR -0.48 (95% CI: -1.23 to 0.27). Based on our descriptives analyses after adjusting for age and comorbidities, the high-risk group in three studies was type 2 diabetes, and in five studies was type 1. Two studies reported no significant difference between these groups in relevant outcomes.ConclusionThere were no significant differences in disease severity between type 1 and type 2 diabetes. Based on the unadjusted data available, the mortality rate for people with type 1 diabetes was shown to be lower than that for people with type 2. As data on these subjects is scarce, and the results obtained from studies are heterogeneous, further research with adequate sample sizes is needed to precisely compare the outcomes of COVID-19 between type 1 and type 2 diabetes.
Project description:BackgroundThe prognostic factors of long-term outcomes in hospitalized patients with diabetes mellitus and COVID-19 are lacking.MethodsIn this retrospective cohort study, we evaluated patients aged ≥ 18-years-old with the COVID-19 diagnosis who were hospitalized between Feb 20 and Oct 29, 2020, in the Sina Hospital, Tehran, Iran. 1323 patients with COVID-19 entered in the final analysis, of whom 393 (29.7%) patients had diabetes. We followed up patients for incurring in-hospital death, severe COVID-19, in-hospital complications, and 7-month all-cause mortality. By doing univariate analysis, variables with unadjusted P-value < 0.1 in univariate analyses were regarded as the confounders to include in the logistic regression models. We made adjustments for possible clinical (model 1) and both clinical and laboratory (model 2) confounders.ResultsAfter multivariable regression, it was revealed that preadmission use of sulfonylureas was associated with a borderline increased risk of severity in both models [model 1, OR (95% CI):1.83 (0.91-3.71), P-value: 0.092; model 2, 2.05 (0.87-4.79), P-value: 0.099] and major adverse events (MAE: each of the severe COVID-19, multi-organ damage, or in-hospital mortality) in model 1 [OR (95% CI): 1.86 (0.90-3.87), P-value: 0.094]. Preadmission use of ACEIs/ARBs was associated with borderline increased risk of MAE in the only model 1 [OR (95% CI):1.83 (0.96-3.48), P-value: 0.066].ConclusionsPreadmission use of sulfonylureas and ACEIs/ARBs were associated with borderline increased risk of in-hospital adverse outcomes.Supplementary informationThe online version contains supplementary material available at 10.1007/s40200-021-00901-4.