Acute-to-chronic glycemic ratio as an outcome predictor in ischemic stroke in patients with and without diabetes mellitus.

OBJECTIVE: Elevated plasma glucose levels are common in patients suffering acute ischemic stroke (AIS), and acute hyperglycemia has been defined as an independent determinant of adverse outcomes. The impact of acute-to-chronic glycemic ratio (ACR) has been analyzed in other diseases, but its impact on AIS prognosis remains unclear. The main aim of this study was to assess whether the ACR was associated with a 3-month poor prognosis in patients with AIS. RESEARCH, DESIGN AND METHODS: Retrospective analysis of patients admitted for AIS in Hospital del Mar, Barcelona. To estimate the chronic glucose levels (CGL) we used the formula eCGL= [28.7xHbA1c (%)]-46.7. The ACR (glycemic at admission / eCGL) was calculated for all subjects. Tertile 1 was defined as: 0.28-0.92, tertile 2: 0.92-1.13 and tertile 3: > 1.13. Poor prognosis at 3 months after stroke was defined as mRS score 3-6. RESULTS: 2.774 subjects with AIS diagnosis were included. Age, presence of diabetes, previous disability (mRS), initial severity (NIHSS) and revascularization therapy were associated with poor prognosis (p values < 0.05). For each 0.1 increase in ACR, there was a 7% increase in the risk of presenting a poor outcome. The 3rd ACR tertile was independently associated with a poor prognosis and mortality. In the ROC curves, adding the ACR variable to the classical clinical model did not increase the prediction of AIS prognosis (0.786 vs. 0.781). CONCLUSIONS: ACR was positively associated with a poor prognosis and mortality at 3-months follow-up after AIS. Subjects included in the 3rd ACR tertile presented a higher risk of poor prognosis and mortality. Baseline glucose or ACR did not add predictive value in comparison to only using classical clinical variables.

Short-term effects of gastric bypass versus sleeve gastrectomy on high LDL cholesterol: The BASALTO randomized clinical trial.

BACKGROUND: There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG). METHODS: In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol < 3.36 nmol/l without lipid-lowering medications. Secondary outcomes included changes in weight, other comorbidities, qualitative lipoprotein traits, cholesterol esters, glycoproteins, cholesterol absorption and synthesis metabolites and complications. RESULTS: Intention-to-treat analysis revealed that LDL cholesterol remission occurred in 66.6% of RYGB patients compared to 27.8% of SG patients (p = 0.019). Among patients completing follow-up, RYGB demonstrated superior remission (80.0% vs. 29.4%, p = 0.005). Exclusive benefits of RYGB included a reduction in large, medium, and small LDL particles. Cholesterol absorption markers showed differential behavior after both techniques: campesterol (Δ -15.2 µg/mg, 95% CI -30.2 to -0.1) decreased after RYGB, and sitosterol (Δ 21.1 µg/mg, 95% CI 0.9 to 41.2), cholestanol (Δ 30.6 µg/mg, 95% CI 14.8 to 57.9) and campesterol (Δ 18.4 µg/mg, 95% CI 4.4 to 32.3) increased after SG. No differences in weight loss, cholesterol esters, glycoproteins, cholesterol synthesis metabolites or postoperative complications were observed between techniques. CONCLUSION: In conclusion, RYGB is superior to SG in terms of short-term of high LDL cholesterol remission. Furthermore, RYGB also led to a greater improvement in lipoprotein parameters that confer an atherogenic profile. Therefore, the presence of elevated levels of LDL cholesterol should be considered when determining the optimal bariatric surgery procedure for each patient. TRIAL REGISTRATION: Clinicaltrials.gov number, NCT03975478).

One abnormal value or vomiting after oral glucose tolerance test in pregnancy: incidence and impact on maternal-fetal outcomes.

OBJECTIVE: To analyze pregnancy outcomes of women with one abnormal value (OAV) during oral glucose tolerance test (OGTT) or OGTT-intolerance, compared with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) pregnant women, according to whether they received any health intervention or not. METHODS: An observational retrospective study was designed including pregnant women who gave birth at Hospital del Mar, Barcelona (Spain) during December/2014-July/2018. Baseline characteristics, pregnancy outcomes and health interventions were obtained from a database collected previously for other study. Inclusion criteria were singleton pregnancies with OAV or OGTT-intolerants who gave birth at the Hospital. GDM screening followed a two-step approach: 50 g O'Sullivan test and 100 g 3-hour OGTT if the former was abnormal. RESULTS: From a total of 2,662 pregnancies, 326 (12.2%) had GDM, 87 OAV (3.3%), 65 OGTT intolerance (2.4%) and 2,184 were NGT women. First trimester HbA1c in both OAV and OGTT-intolerant women was significantly higher than in NGT group, and significantly lower than in GDM pregnants. No differences in obstetric outcomes were found between OGTT-intolerants and NGT/GDM groups. Treated OGTT-intolerants had greater gestational age at delivery than non-treated ones (weeks, 39.6 ± 1.2 vs 38.0 ± 4.0, respectively). In OAV women, significant differences were observed in newborns' birthweight (g, 3227.3 ± 500.8 vs 3351.1 ± 436.7, vs GDM) and gestational age at birth (weeks, 38.7 ± 1.8 vs 39.3 ± 1.9, vs NGT), but not in macrosomia/pre-eclampsia. No differences were found according to treatment in OAV. CONCLUSIONS: OAV and OGTT-intolerants account for a third of pregnant women referred to Diabetes Unit. Their rates of preterm birth, pre-eclampsia and macrosomia were not different from NGT or GDM women.

The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19).

BACKGROUND: It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. METHODS: We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020-October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. RESULTS: Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83-2.45 with an I2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29-1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31-0.75], I2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40-0.68], I2 37%) were significantly lower for people with previous macrovascular disease. CONCLUSIONS: This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup.

Impact of overt diabetes diagnosed in pregnancy in a multi-ethnic cohort in Spain.

Overt diabetes (ODM) is defined as women without diabetes meeting the criteria for diabetes at the first antenatal visit. The risk of obstetric complications increases linearly with maternal glycemia and poorer maternal-fetal outcomes than in gestational diabetes (GDM) may be expected. Studies focusing on ODM pregnancy outcomes are lacking. We aimed to analyze maternal characteristics and pregnancy outcomes in ODM women compared with those with GDM. A retrospective cohort study of women giving birth between January 2010 and April 2013 was conducted. Participants with pre-gestational diabetes were excluded. All women underwent screening for GDM at the 24th-28th weeks of gestation or at the first prenatal visit in those with risk factors. HbA1c and a fasting glucose were measured in GDM women to rule out ODM. Of the 5,633 women included, 572 (10%) were diagnosed with GDM and 50 (0.88%) with ODM. Almost 95% of ODM women were from ethnic minorities. After adjustment for confounding factors, ODM women showed increased rates of premature birth (23.1% vs. 6.7%, p < .001), emergent cesarean section (41.0% vs. 19.5%, p = .049), preeclampsia (22% vs. 3.7%, p < .001) and large-for-gestational-age babies (40.0% vs. 14.8%, p = .008) compared with GDM. In conclusion, ODM is associated with poorer obstetric outcomes than GDM and affects mainly women from ethnic minorities.

Circulating triacylglycerol signatures and insulin sensitivity in NAFLD associated with the E167K variant in TM6SF2.

BACKGROUND & AIMS: The Glu167Lys (E167K) variant in the transmembrane 6 superfamily member 2 protein (TM6SF2) was recently shown to influence liver fat (LFAT) content. We aimed at studying how this variant influences circulating triacylglycerol (TAG) signatures and whether it influences hepatic or adipose tissue insulin sensitivity. METHODS: We genotyped 300 Finnish subjects for the E167K (rs58542926) variant in TM6SF2 and for the I148M (rs738409) variant in the patatin-like phospholipase domain-containing protein 3 (PNPLA3) in whom LFAT was measured using 1H-MRS and circulating lipids by UPLC-MS. We compared the plasma lipidome between E167K carriers (TM6SF2EK/KK) and non-carriers (TM6SF2EE), and between three groups of NAFLD: (i) carriers of the E167K but not of the I148M variant in PNPLA3 ('TM6SF2 NAFLD'), (ii) carriers of the I148M but not of the E167K variant ('PNPLA3 NAFLD'), and (iii) non-carriers of either risk allele ('Non-risk NAFLD'). Hepatic and adipose tissue insulin sensitivities were measured using the euglycemic hyperinsulinemic clamp technique combined with infusion of [3-3H]glucose in 111 subjects. RESULTS: The LFAT content was 34% higher in the TM6SF2EK/KK (13.07±1.57%) than in the TM6SF2EE group (9.77±0.58%, p=0.013). The effect of insulin on glucose production and lipolysis were significantly higher in the TM6SF2EK/KK than in the TM6SF2EE group. Comparison of the three NAFLD groups with similar LFATs showed that both the 'TM6SF2 NAFLD' and 'PNPLA3 NAFLD' had significantly lower triglyceride levels and were characterized by lower levels of most common TAGs compared to the 'Non-risk NAFLD' group. CONCLUSIONS: We conclude that the E167K variant in TM6SF2 is associated with a distinct subtype of NAFLD, characterized by preserved insulin sensitivity with regard to lipolysis, hepatic glucose production and lack of hypertriglyceridemia despite a clearly increased LFAT content.

Haptoglobin genotype is associated with increased endothelial dysfunction serum markers in type 1 diabetes.

BACKGROUND: To evaluate the genotype-driven effect of haptoglobin (Hp) in patients with type 1 diabetes without clinical cardiovascular (CV) disease, considering endothelial dysfunction (ED) and arterial stiffness (AS). MATERIAL AND METHODS: About 137 patients with type 1 diabetes (duration ≥ 5 years) and 68 age- and sex-matched controls were evaluated for the following: (i) smoking, alcohol intake, BMI, blood pressure, fasting plasma glucose, HbA1c and lipid profile; (ii) microvascular complications; (iii) serum markers of ED (ICAM-1, VCAM-1 and E-selectin); (iv) AS, assessed as aortic pulse wave velocity (aPWV); and (v) Hp genotype. RESULTS: The prevalence of the 1/1, 2/1 and 2/2 Hp genotypes was 28.5%, 46.7% and 24.8% in patients with type 1 diabetes and 20.9%, 38.8% and 40.3% in controls, respectively. No differences were found in classical CV risk factors between patients homozygous for allele 2 and the remaining genotypes, both in patients with type 1 diabetes and controls. Patients with type 1 diabetes carrying the Hp2/2 genotype had higher concentrations of ICAM-1 (65.1 (56.7-76.0) ng/mL vs. 59.0 (51.7-69.3) ng/mL; P = 0.033) and sVCAM-1 (1133.1 (884.6-1458.6) ng/mL vs. 956.4 (738.5-1206.1) ng/mL; P = 0.040) than those without it. The Hp2/2 genotype remained independently associated with ED after adjusting for CV risk factors (P = 0.038). No significant differences were found for aPWV between Hp genotypes. CONCLUSIONS: Endothelial dysfunction may be influenced by Hp2/2 genotype in patients with type 1 diabetes with independence of classical CV risk factors.

Reduced circulating levels of TWEAK are associated with gestational diabetes mellitus.

BACKGROUND: To evaluate the inflammatory axis mediated by tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its scavenger receptor CD163 during pregnancy and their influence on insulin sensitivity in normal pregnancy and in gestational diabetes mellitus (GDM). MATERIALS AND METHODS: One hundred and thirty seven women with one singleton pregnancy, 71 with normal glucose tolerance (NGT) and 66 with GDM were studied. Glucose metabolism was assessed by oral glucose tolerance test. Serum concentrations of soluble TWEAK (sTWEAK) and CD163 (sCD163) and insulin resistance (HOMA-IR index) were determined in maternal blood drawn at recruitment, in the early third trimester. Offspring weight and height were assessed at birth. RESULTS: Women with GDM had lower circulating sTWEAK concentrations than control NGT group (237·8 (192·1-301·0) pg/mL vs. 277·2 (206·4-355·7) pg/mL; P = 0·013). sTWEAK was negatively associated with the presence of GDM (r = -0·212; P = 0·013), HOMA-IR index (r = -0·197; P = 0·021) and ponderal index of the newborn (r = -0·196; P = 0·025), but positively with HDL cholesterol (r = 0·283; P = 0·001). In multiple regression analysis, sTWEAK concentration emerged as one of the main predictors of insulin resistance, along with BMI, triglycerides and low concentrations of HDL cholesterol (R(2)  = 0·486; P < 0·001). No relationship was found between HOMA-IR index and sCD163 or sCD163/sTWEAK ratio. CONCLUSIONS: sTWEAK concentrations are lower in patients with GDM compared with healthy pregnant women, and low concentrations of sTWEAK are associated with insulin resistance. These findings suggest that insulin resistance during pregnancy is closely linked to inflammatory imbalance and sTWEAK may represent a new candidate associated with GDM.

Telehealth model versus in-person standard care for persons with type 1 diabetes treated with multiple daily injections: an open-label randomized controlled trial.

Objective: Increasing evidence indicates that the telehealth (TH) model is noninferior to the in-person approach regarding metabolic control in type 1 diabetes (T1D) and offers advantages such as a decrease in travel time and increased accessibility for shorter/frequent visits. The primary aim of this study was to compare the change in glycated hemoglobin (HbA1c) at 6 months in T1D care in a rural area between TH and in-person visits. Research design and methods: Randomized controlled, open-label, parallel-arm study among adults with T1D. Participants were submitted to in-person visits at baseline and at months 3 and 6 (conventional group) or teleconsultation in months 1 to 4 plus 2 in-person visits (baseline and 6 months) (TH group). Mixed effects models estimated differences in HbA1c changes. Results: Fifty-five participants were included (29 conventional/26 TH). No significant differences in HbA1c between groups were found. Significant improvement in time in range (5.40, 95% confidence interval (CI): 0.43-10.38; p < 0.05) and in time above range (-6.34, 95% CI: -12.13- -0.55;p < 0.05) in the TH group and an improvement in the Diabetes Quality of Life questionnaire (EsDQoL) score (-7.65, 95% CI: -14.67 - -0.63; p < 0.05) were observed. In TH, the costs for the participants were lower. Conclusions: The TH model is comparable to in-person visits regarding HbA1c levels at the 6-month follow-up, with significant improvement in some glucose metrics and health-related quality of life. Further studies are necessary to evaluate a more efficient timing of the TH visits.

Validity and Applicability of the Global Leadership Initiative on Malnutrition (GLIM) Criteria in Patients Hospitalized for Acute Medical Conditions.

(1) Background: The objectives of this study were to evaluate the concurrent and predictive validity and the applicability of the global leadership initiative on malnutrition (GLIM) criteria in patients hospitalized for acute medical conditions. (2) Methods: prospective cohort study with patients hospitalized for acute medical conditions. For validation, the methodology proposed by the GLIM group of experts was used. Sensitivity and specificity values greater than 80% with respect to those for the subjective global assessment (SGA) were necessary for concurrent validation. The time necessary to complete each nutritional assessment test was determined. (3) Results: A total of 119 patients were evaluated. The SGA was applied to the entire cohort, but the GLIM criteria could not be applied to 3.4% of the patients. The sensitivity and specificity of the GLIM criteria with respect to those for the SGA to detect malnutrition were 78.0 and 86.2%, respectively. The GLIM predictive validity criterion was fulfilled because patients with malnutrition more frequently had a hospital stay >10 days (odds ratio of 2.98 (1.21-7.60)). The GLIM criteria required significantly more time for completion than did the SGA (p = 0.006). (4) Conclusion: The results of this study do not support the use of the GLIM criteria over the SGA for the diagnosis of malnutrition in patients hospitalized for acute medical conditions.

Protective effects of the succinate/SUCNR1 axis on damaged hepatocytes in NAFLD.

OBJECTIVE: Succinate and succinate receptor 1 (SUCNR1) are linked to fibrotic remodeling in models of non-alcoholic fatty liver disease (NAFLD), but whether they have roles beyond the activation of hepatic stellate cells remains unexplored. We investigated the succinate/SUCNR1 axis in the context of NAFLD specifically in hepatocytes. METHODS: We studied the phenotype of wild-type and Sucnr1-/- mice fed a choline-deficient high-fat diet to induce non-alcoholic steatohepatitis (NASH), and explored the function of SUCNR1 in murine primary hepatocytes and human HepG2 cells treated with palmitic acid. Lastly, plasma succinate and hepatic SUCNR1 expression were analyzed in four independent cohorts of patients in different NAFLD stages. RESULTS: Sucnr1 was upregulated in murine liver and primary hepatocytes in response to diet-induced NASH. Sucnr1 deficiency provoked both beneficial (reduced fibrosis and endoplasmic reticulum stress) and detrimental (exacerbated steatosis and inflammation and reduced glycogen content) effects in the liver, and disrupted glucose homeostasis. Studies in vitro revealed that hepatocyte injury increased Sucnr1 expression, which when activated improved lipid and glycogen homeostasis in damaged hepatocytes. In humans, SUCNR1 expression was a good determinant of NAFLD progression to advanced stages. In a population at risk of NAFLD, circulating succinate was elevated in patients with a fatty liver index (FLI) ≥60. Indeed, succinate had good predictive value for steatosis diagnosed by FLI, and improved the prediction of moderate/severe steatosis through biopsy when added to an FLI algorithm. CONCLUSIONS: We identify hepatocytes as target cells of extracellular succinate during NAFLD progression and uncover a hitherto unknown function for SUCNR1 as a regulator of hepatocyte glucose and lipid metabolism. Our clinical data highlight the potential of succinate and hepatic SUCNR1 expression as markers to diagnose fatty liver and NASH, respectively.

Acute-to-Chronic Glycemic Ratio as a Predictor of COVID-19 Severity and Mortality.

OBJECTIVE: To evaluate the association between acute-to-chronic (A/C) glycemic ratio and mortality and severity outcomes for patients with type 2 diabetes (T2D) hospitalized with coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: A total of 91 patients were included. We measured glycemia at admission and estimated the average chronic glucose levels to calculate the A/C glycemic ratio. The primary outcome was a composite of in-hospital mortality, intensive care unit admission, and mechanical ventilation. RESULTS: Thirty-five patients had a primary outcome event, presenting a significant association with the A/C glycemic ratio (hazard ratio [HR] 1.57 [95% CI 1.14-2.15], P = 0.005). In comparisons with the 2nd tertile, the 3rd tertile of the A/C glycemic ratio was associated with the primary outcome (HR 3.39 [95% CI 1.31-8.75], P = 0.012). In the multivariate analysis, after additional adjustment for age, sex, comorbidities, inflammatory markers, and corticosteroid therapy, the association for the 3rd tertile (HR 3.96 [95% CI 1.35-11.59], P = 0.012) remained significant. CONCLUSIONS: In patients with T2D hospitalized with COVID-19, the imbalance between acute glycemia at admission and chronic metabolic control is associated with worse prognosis.

Measurement of Serum N-Glycans in the Assessment of Early Vascular Aging (Arterial Stiffness) in Adults With Type 1 Diabetes.

OBJECTIVE: Vascular aging (arterial stiffness [AS]) is an inflammation-linked process that predicts macro- and microvascular complications in adults with type 1 diabetes (T1D). We evaluated the utility of measuring the inflammation-linked N-glycans GlycA and GlycB to assess vascular aging in adults with T1D. RESEARCH DESIGN AND METHODS: Eighty-four adults with T1D (>10-year duration without cardiovascular events) and 68 healthy control subjects were evaluated for clinical characteristics (including microvascular complications in patients with T1D), aortic pulse wave velocity (aPWV) (surrogate measure of AS), and serum GlycA and GlycB (peak area [concentration] and height/width [H/W] ratio) using 1H-nuclear magnetic resonance spectroscopy. RESULTS: Patients with T1D had higher median (interquartile range) values than healthy control subjects for (P < 0.001 for all comparisons) aPWV 7.9 (6.9-9.1) vs. 6.1 (5.5-6.7) m/s, GlycA 850.4 (781.3-916.1) vs. 652.4 (581.5-727.1) µmoL; GlycB 386.1 (353.2-426.3) vs. 310.0 (280.5-331.9) µmol/L), H/W ratio of GlycA 16.5 (14.9-18.1) vs. 15.0 (13.7-16.7), and H/W ratio of GlycB 5.0 (4.6-5.5) vs. 4.0 (3.4-4.3). Moreover, aPWV correlated (P < 0.001 for all correlations) with GlycA (r = 0.550) and GlycB (r = 0.423) concentrations and with H/W ratios of GlycA (r = 0.453) and GlycB (r = 0.510). Adjusting for potential confounders, GlycA concentration (ß = 0.212, P < 0.001) and the H/W ratios of GlycA (ß = 0.150, P = 0.009) and GlycB (ß = 0.155, P = 0.011) remained independently associated with aPWV. C-statistics for detecting individuals with aPWV >10 m/s were 0.866 (95% CI 0.794-0.937) for GlycA levels and 0.862 (0.780-0.943) for H/W ratio of GlycB. CONCLUSIONS: Measurement of serum GlycA and GlycB may have utility in assessing vascular aging in adults with T1D of >10-year duration and no previous cardiovascular events.

Individuals With Higher CD4/CD8 Ratio Exhibit Increased Risk of Acute Respiratory Distress Syndrome and In-Hospital Mortality During Acute SARS-CoV-2 Infection.

Background: CD4/CD8 ratio has been used as a quantitative prognostic risk factor in patients with viral infections. This study aims to assess the association between in-hospital mortality and at admission CD4/CD8 ratio among individuals with acute SARS-CoV-2 infection. Methods: This is a longitudinal cohort study with data of all consecutive patients admitted to the COVID-19 unit at Hospital del Mar, Barcelona, Spain for ≥48 h between March to May 2020. The CD4+ CD8+ T-cell subset differentiation was assessed by flow cytometry at admission as well as a complete blood test. Patients were classified according to CD4/CD8 ratio tertiles. The primary outcome was in-hospital mortality and the secondary outcome was acute respiratory distress (ARDS). Results: A total of 338 patients were included in the cohort. A high CD4/CD8 ratio (third tertile) was associated with a higher in-hospital mortality [adjusted Cox model hazard ratio (HR) 4.68 (95%CI 1.56-14.04, p = 0.006), reference: second tertile HR 1]. Similarly, a high CD4/CD8 ratio (third tertile) was associated with a higher incidence of ARDS [adjusted logistic regression model OR 1.97 (95%CI 1.11-3.55, p = 0.022) reference: second tertile HR 1]. There was a trend of higher in-hospital mortality and incidence of ARDS in patients within the first tertile of CD4/CD8 ratio compared with the second one, but the difference was not significant. No associations were found with total lymphocyte count or inflammatory parameters, including D-dimer. Conclusion: CD4/CD8 ratio is a prognostic factor for the severity of COVID-19, reflecting the negative impact on prognosis of those individuals whose immune response has abnormal CD8+ T-cell expansion during the early response to the infection.

Association of statin and/or renin-angiotensin-aldosterone system modulating therapy with mortality in adults with diabetes admitted to hospital with COVID-19: A retrospective multicentre European study.

BACKGROUND & AIMS: To assess the impact of pre-admission renin-angiotensin-aldosterone system inhibitor (RAASi) and statin use on mortality following COVID-19 hospitalization in adults with pre-existing diabetes. METHODS: Retrospective cohort study of adults with diabetes admitted to ninety-nine participating hospitals in the United Kingdom, France and Spain during the first wave of the COVID-19 pandemic. Logistic regression models adjusted for demographic factors and comorbidity were used to describe associations with mortality in hospital or within 28 days of admission and individual or combined RAASi and statin therapy prescription followed by a country level meta-analysis. RESULTS: Complete data were available for 3474 (42.6%) individuals. Prescribing patterns varied by country: 25-50% neither RAASi nor statin therapy, 14-36% both RAASi and statin therapy, 9-24% RAASi therapy alone, 12-36% statin alone. Overall, 20-37% of patients died within 28 days. Meta-analysis found no evidence of an association between mortality and prescription of RAASi therapy (OR 1.09, CI 0.78-1.52 (I2 22.2%)), statin (OR 0.97, CI 0.59-1.61 (I2 72.9%)) or both (OR 1.14, CI 0.67-1.92 (I2 78.3%)) compared to those prescribed neither drug class. CONCLUSIONS: This large multicentre, multinational study found no evidence of an association between mortality from COVID-19 infection in people with diabetes and use of either RAASi, statin or combination therapy. This provides reassurance that clinicians should not change their RAASi and statin therapy prescribing practice in people with diabetes during the COVID-19 pandemic.

Interpretation of clinical trials on the cardiovascular effects of hypoglycemic drugs in people with type2 diabetes. / Interpretación de los ensayos clínicos sobre efectos cardiovasculares de los fármacos hipoglucemiantes en personas con diabetes tipo2.

Randomized clinical trials on the cardiovascular effects of hypoglycemic drugs on people with type2 diabetes mellitus began more than fifty years ago. In the last decade, the emergence of new classes of hypoglycemic drugs has led to the development of randomized clinical trials to assess their cardiovascular safety. Known as Cardiovascular Outcome Trials, they have provided a lot of new information that needs to be critically appraised if the knowledge obtained is to be applicable in clinical practice. To this end, the current article first comments on the guidelines to which these trials have adhered, then reviews some concepts for improving their interpretation (such as different types of analyses, the definition of objectives and the evaluation of their results), and concludes by mentioning the new guidelines to which future trials designed to evaluate the safety of new hypoglycemic drugs should adhere.

Interpretation of clinical trials on the cardiovascular effects of hypoglycemic drugs in people with type 2 diabetes.

Randomized clinical trials on the cardiovascular effects of hypoglycemic drugs on people with type 2 diabetes mellitus began more than fifty years ago. In the last decade, the emergence of new classes of hypoglycemic drugs has led to the development of randomized clinical trials to assess their cardiovascular safety. Known as Cardiovascular Outcome Trials, they have provided a lot of new information that needs to be critically appraised if the knowledge obtained is to be applicable in clinical practice. To this end, the current article first comments on the guidelines to which these trials have adhered, then reviews some concepts for improving their interpretation (such as different types of analyses, the definition of objectives and the evaluation of their results), and concludes by mentioning the new guidelines to which future trials designed to evaluate the safety of new hypoglycemic drugs should adhere.

Arterial Stiffness in Type 1 Diabetes: The Case for the Arterial Wall Itself as a Target Organ.

Arterial stiffness (AS) integrates the cumulative burden of known and unknown cardiovascular risk factors on the elastic wall of large arteries along the lifespan of an individual. As a marker of vascular aging, AS is an independent predictor of cardiovascular events and improves cardiovascular risk prediction when added to the Framingham Risk Score. In addition, AS may affect the microvasculature and promote the development of microvascular complications. Its impact on both the macro- and microvasculature has led to the concept that the arterial wall itself should be considered as a target organ. Here, we review the biological and clinical consequences of AS on the macro- and microvasculature and the measurement of AS in routine clinical practice. We also discuss the pathophysiological mechanisms underpinning AS development using diabetes and, in particular, type 1 diabetes, as a disease model with a high risk of cardiovascular events and microvascular complications that are accelerated by AS.

Prognostic Value of the Acute-to-Chronic Glycemic Ratio at Admission in Heart Failure: A Prospective Study.

Acute hyperglycemia has been associated with worse prognosis in patients hospitalized for heart failure (HF). Nevertheless, studies evaluating the impact of glycemic control on long-term prognosis have shown conflicting results. Our aim was to assess the relationship between acute-to-chronic (A/C) glycemic ratio and 4-year mortality in a cohort of subjects hospitalized for acute HF. A total of 1062 subjects were consecutively included. We measured glycaemia at admission and estimated average chronic glucose levels and the A/C glycemic ratio were calculated. Subjects were stratified into groups according to the A/C glycemic ratio tertiles. The primary endpoint was 4-year mortality. Subjects with diabetes had higher risk for mortality compared to those without (HR 1.35 [95% CI: 1.10-1.65]; p = 0.004). A U-shape curve association was found between glucose at admission and mortality, with a HR of 1.60 [95% CI: 1.22-2.11]; p = 0.001, and a HR of 1.29 [95% CI: 0.97-1.70]; p = 0.078 for the first and the third tertile, respectively, in subjects with diabetes. Additionally, the A/C glycemic ratio was negatively associated with mortality (HR 0.76 [95% CI: 0.58-0.99]; p = 0.046 and HR 0.68 [95% CI: 0.52-0.89]; p = 0.005 for the second and third tertile, respectively). In multivariable analysis, the A/C glycemic ratio remained an independent predictor. In conclusion, in subjects hospitalized for acute HF, the A/C glycemic ratio is significantly associated with mortality, improving the ability to predict mortality compared with glucose levels at admission or average chronic glucose concentrations, especially in subjects with diabetes.

Previous Vitamin D Supplementation and Morbidity and Mortality Outcomes in People Hospitalised for COVID19: A Cross-Sectional Study.

Aim: The study aim was to assess the association of vitamin D supplementation before hospital admission and severe outcomes in subjects admitted for COVID-19. Methods: We performed a cross-sectional analysis of pseudonymised medical record data from subjects admitted to the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) for COVID-19 during March and April 2020. The composite primary study outcome was defined as death and/or invasive mechanical ventilation (IMV). Association between risk factors and study outcomes was evaluated by bivariate analysis, followed by logistic regression analysis. Results: In total, 1,267 persons were hospitalised during the observation period. Overall, 14.9% of the subjects were on active vitamin D supplementation treatment before admission. The subjects in the vitamin D group were significantly older than subjects without vitamin D supplementation. We observed higher rates of the primary outcome (death and/or IMV) among the persons with previous use of vitamin D (30.1 vs. 22.9% in those not receiving treatment). In the bivariate analysis, previous use of vitamin D was positively associated with death and/or IMV [odds ratio (OR): 1.45 95% CI: 1.03; 2.04]; however, after adjustment for other risk factors this association disappeared (OR: 1.09 95%CI: 0.65; 1.81). Conclusion: We did not find an association between vitamin D supplementation before hospital admission and death and/or IMV in subjects admitted for COVID-19. The age and the burden of age-associated comorbidities were independently associated with the in-hospital events.