Contrasting data have been published about the impact of cardiovascular disease on Covid-19. A comprehensive synthesis and pooled analysis of the available evidence is needed to guide prioritization of prevention strategies. To clarify the association of cardiovascular disease with Covid-19 outcomes, we searched PubMed up to 26 October 2020, for studies reporting the prevalence of cardiovascular disease among inpatients with Covid-19 in relation to their outcomes. Pooled odds-ratios (OR) for death, for mechanical ventilation or admission in an intensive care unit (ICU) and for composite outcomes were calculated using random effect models overall and in the subgroup of people with comorbid diabetes. Thirty-three studies enrolling 52,857 inpatients were included. Cardiovascular disease was associated with a higher risk of death both overall (OR 2.58, 95% confidence intervals, CI 2.12–3.14, p < 0.001, number of studies 24) and in the subgroup of people with diabetes (OR 2.91, 95% CI 2.13–3.97, p < 0.001, number of studies 4), but not with higher risk of ICU admission or mechanical ventilation (OR 1.35, 95% CI 0.73–2.50, p = 0.34, number of studies 4). Four out of five studies reporting OR adjusted for confounders failed to show independent association of cardiovascular disease with Covid-19 deaths. Accordingly, the adjusted-OR for Covid-19 death in people with cardiovascular disease dropped to 1.31 (95% CI 1.01–1.70, p = 0.041). Among patients hospitalized for Covid-19, cardiovascular disease confers higher risk of death, which was highly mitigated when adjusting the association for confounders.

Introduction Diabetes mellitus worsens the prognosis of SARS‐CoV‐2 infection, and vaccination has been the major tool for reducing the risk of hospitalisation, and mortality. The primary aim of this study was to evaluate the response to the SARS‐CoV‐2 vaccine in subjects with diabetes and controls. Differences between type 1 (T1D) and type 2 (T2D) diabetes and clinical determinants of vaccination response were also evaluated. Methods 128 subjects with diabetes (60 with T1D and 62 with T2D) and 202 subjects acting as controls who completed a full vaccination cycle with two doses of mRNA vaccine were enroled. People with previous SARS‐CoV‐2 infection were excluded. Antibodies (Ab) directed against the spike protein of the SARS‐CoV‐2 were evaluated at one and 6 months after vaccination. Results In the whole cohort, the Ab level was higher among women than in men ( p = 0.011) and negatively correlated with age (rho = −0.155, p = 0.005). Subjects with diabetes showed decreased levels of Ab after one month compared to controls (1217[747–1887]BAU/mL vs. 1477[942–2556]BAU/mL, p = 0.002), even after correction for age and gender ( p = 0.002). No difference was found between subjects with T1D and T2D. After 6 months, antibody levels significantly decreased in people with and without diabetes, with no differences between groups, although some subjects were lost at follow‐up. In subjects with diabetes, only a significant correlation was found between Ab level and renal function (rho 0.190, p = 0.042). Conclusions Both T1D and T2D are associated with a reduced early response to vaccination. The serum concentration of Ab significantly reduced over time in both groups, highlighting the relevance of vaccination boosters independently of the presence of diabetes.

Background Novel biomarkers of vascular disease in diabetes could help identify new mechanistic pathways. Osteocalcin, osteoprotegerin, and osteopontin are key molecules involved in bone and vascular calcification processes, both of which are compromised in diabetes. We aimed to evaluate possible associations of osteocalcin, osteoprotegerin, and osteopontin with cardiovascular disease (CVD) and diabetic retinopathy (DR) among people with type 2 diabetes (T2D). Materials and Methods Osteocalcin, osteoprotegerin, and osteopontin concentrations were measured at enrolment in 848 participants with T2D from the Sapienza University Mortality and Morbidity Event Rate (SUMMER) Study (ClinicalTrials.gov: NCT02311244). Logistic regression models and propensity score matching were used to assess possible associations of osteocalcin, osteoprotegerin, and osteopontin with a history of CVD and with evidence of any grade of DR adjusting for confounders. Results Previous CVD was reported in 139 (16.4%) participants, while 144 (17.0%) had DR. After adjusting for possible confounders, osteocalcin but not osteoprotegerin or osteopontin concentrations were associated with a history of CVD (Odds Ratio [OR] and 95% CI for one standard deviation (SD) increase in osteocalcin concentrations (natural log): 1.35 (1.06–1.72), p = 0.014). Associations with prevalent DR were seen for osteoprotegerin (OR for one SD increase in osteoprotegerin concentrations (natural log): 1.25 (1.01–1.55), p = 0.047) and osteopontin (OR for one SD increase in osteopontin concentrations (natural log): 1.25 (1.02–1.53), p = 0.022), but not osteocalcin. Conclusions In T2D, higher serum osteocalcin concentrations are associated with macrovascular complications and higher osteoprotegerin and osteopontin concentrations with microvascular complications, suggesting that these osteokines might be involved in pathways directly related to vascular disease.

Background: Autoimmune diabetes (AD) results from a loss of immune tolerance leading to the destruction of β-cells in the pancreas. Heterogeneity in severity of β-cell damage among people with AD is well-recognized, with some patients retaining a certain amount of insulin-producing cells for years despite the presence of pancreatic autoimmunity. Cellular and molecular mechanisms driving the preservation of β-cell function in AD remain unclear. Aim & Methods: To identify metabolic pathways associated with preservation of β-cell function we conducted a metabolomic study using gas and liquid chromatography-mass spectrometry (GC- and LC-MS) based platform on plasma samples collected from 32 subjects with adult-onset AD (median [Q1-Q3] age: 57 [52-62]; disease duration: 4.5 [3.0-9.0] years) with different severity of β-cell dysfunction, compared with data from people with rheumatoid arthritis (RA, n=28). Metabolome profiles of pancreatic islets from healthy donors after in vitro treatment with proinflammatory cytokines was also evaluated. Results: Metabolomic analyses showed decreased plasma Kynurenine/Tryptophan ratio (KynTr), a marker of indoleamine 2,3 dioxygenase-1 (IDO1) activity, in people with AD compared to RA (0.023 vs 0.027, p=0.03). Among people with AD, KynTr was directly associated with fasting C-peptide levels (rho=0.365), independently of age, gender, body mass index, diabetes duration and Hba1c (p-value after adjustments= 0.003). Lower concentrations of Tryptophan was observed in pancreatic islets from healthy donors after treatment with proinflammatory cytokines. Conclusions: While confirming that IDO1 impairment is involved in the pathogenesis of AD and in the regulation of inflammatory response of pancreatic islets, our results show that KynTr is a marker of beta-cell damage in AD. Overall, this suggests that the kynurenine pathway may be studied as a possible target for therapies aimed at preserving beta-cell function also after a diagnosis of AD Disclosure E. Maddaloni: Consultant; Abbott, Merck KGaA, PIKDARE S. p. A., Speaker's Bureau; Medical Technology & Devices. F. Dotta: None. P. Marchetti: None. R. Buzzetti: None. A. Gastaldelli: Advisory Panel; Pfizer Inc., Novo Nordisk, Merck Sharp & Dohme Corp., Boehringer Ingelheim International GmbH, Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Fractyl Health, Inc., Merck Sharp & Dohme Corp., Other Relationship; Pfizer Inc., Speaker's Bureau; Eli Lilly and Company. L. Navarini: Consultant; AbbVie Inc., Pfizer Inc., Bristol Myers, Celgene, MSD Life Science Foundation, Eli Lilly and Company, Novartis, Janssen Global Services, LLC. R. Amendolara: None. S. Fenizia: None. S. Pezzica: None. M. Tesi: None. L. D'onofrio: None. E. Bosi: None. Funding Italian Ministry of University and Research (PRIN 2017: 20175L9H7H)