•The vitamin D endocrine system have a variety of actions on cells and tissues involved in COVID-19 progression.•Early calcifediol (25-hydroxyvitamin D) treatment to hospitalized COVID-19 patients ...significantly reduced intensive care unit admissions-Calcifediol seems to be able to reduce severity of the COVID-19.•Calcifediol seems to be able to reduce severity of the disease.
The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19.
Parallel pilot randomized open label, double-masked clinical trial.
University hospital setting (Reina Sofia University Hospital, Córdoba Spain.)
76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1).
All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths.
Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002−0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged.
Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.
Background
We try to explore whether long‐term consumption of two healthy dietary patterns (low‐fat LF diet or Mediterranean diet MedDiet) interacts with the apolipoprotein E (APOE) single‐nucleotide ...polymorphisms (SNPs: rs439401, rs440446 and rs7412) modulating postprandial hypertriglyceridemia (ppHTG) in coronary heart disease (CHD) patients.
Methods and results
We selected patients from the CORDIOPREV study with genotyping and who underwent an oral fat load test (FLT) at baseline and after 3 years follow‐up (n = 506). After 3 years of follow‐up, we found a gene‐diet interaction between the APOE rs439401 SNP and MedDiet. Specifically, T‐allele carriers in the MedDiet group showed a more significant decrease in postprandial triglycerides (TG: P = 0.03) and large triacylglycerol‐rich lipoproteins (TRLs) TG (large TRLs TG; P = 0.01) compared with CC subjects. Consistently, the area under the curve of TG (AUC‐TG; P‐interaction = 0.03) and AUC‐large TRLs TG (P‐interaction = 0.02) were significantly lower in T‐allele carriers compared with CC subjects.
Conclusions
The long‐term consumption of a MedDiet modulates ppHTG through APOE genetic variants in CHD patients. This gene‐diet interaction may contribute to a more precise dietary advice in CHD patients.
Background and objectives
A Mediterranean lifestyle may prevent and mitigate cardiometabolic disorders. We explored whether adherence to a Mediterranean lifestyle was prospectively associated with ...the risk of metabolic syndrome (MetS) among coronary heart disease (CHD) patients.
Methods
The Coronary Diet Intervention with Olive Oil and Cardiovascular Prevention (CORDIOPREV) study was an interventional diet study to compare a Mediterranean diet with a low‐fat diet, in 1002 CHD patients. The Mediterranean lifestyle (MEDLIFE) index was used to assess adherence to a MEDLIFE at baseline, and after 5 years, in 851 participants from the CORDIOPREV study. Subjects were classified as having high (>13 points), moderate (12–13 points), and low (<12 points) adherence to the MEDLIFE. Multivariable logistic regression models were used to determine the association between MEDLIFE adherence and the risk of MetS development or reversal.
Results
During the 5‐year follow‐up, CORDIOPREV participants with high adherence to MEDLIFE had a lower risk of MetS development (odds ratio OR 0.37, 95% confidence interval CI 0.19–0.75, p < 0.01) and a higher likelihood of reversing preexisting MetS (OR 2.08 CI 95% 1.11–3.91, p = 0.02) compared with participants in the low MEDLIFE adherence group. Each additional one‐point increment in the MEDLIFE index was associated with a 24% lower risk of MetS development (OR 0.76, 95% CI 0.64–0.90, p < 0.01) and a 21% higher likelihood of reversing preexisting MetS (OR 1.21 CI 95% 1.04–1.41, p = 0.01).
Conclusions
Our results showed that greater adherence to a MEDLIFE reduced the risk of subsequent MetS development and increased the likelihood of reversing preexisting MetS among patients with CHD at baseline.
We aimed to explore whether changes in circulating levels of miRNAs according to type 2 diabetes mellitus (T2DM) or prediabetes status could be used as biomarkers to evaluate the risk of developing ...the disease. The study included 462 patients without T2DM at baseline from the CORDIOPREV trial. After a median follow-up of 60 months, 107 of the subjects developed T2DM, 30 developed prediabetes, 223 maintained prediabetes and 78 remained disease-free. Plasma levels of four miRNAs related to insulin signaling and beta-cell function were measured by RT-PCR. We analyzed the relationship between miRNAs levels and insulin signaling and release indexes at baseline and after the follow-up period. The risk of developing disease based on tertiles (T1-T2-T3) of baseline miRNAs levels was evaluated by COX analysis. Thus, we observed higher miR-150 and miR-30a-5p and lower miR-15a and miR-375 baseline levels in subjects with T2DM than in disease-free subjects. Patients with high miR-150 and miR-30a-5p baseline levels had lower disposition index (p = 0.047 and p = 0.007, respectively). The higher risk of disease was associated with high levels (T3) of miR-150 and miR-30a-5p (HR
= 4.218 and HR
= 2.527, respectively) and low levels (T1) of miR-15a and miR-375 (HR
= 3.269 and HR
= 1.604, respectively). In conclusion, our study showed that deregulated plasma levels of miR-150, miR-30a-5p, miR-15a, and miR-375 were observed years before the onset of T2DM and pre-DM and could be used to evaluate the risk of developing the disease, which may improve prediction and prevention among individuals at high risk for T2DM.
Scope
Single nucleotide polymorphisms (SNPs) of the circadian locomotor output cycles kaput (CLOCK) gene have been associated with cardiometabolic conditions such as obesity and dyslipidemia. Our aim ...was to examine whether the chronic consumption of two healthy diets interacts with SNPs of the CLOCK gene in order to improve lipid metabolism and inflammation status in patients with coronary heart disease (CHD).
Methods and results
The diets were low‐fat (LF) diet and Mediterranean diet (MedDiet). CLOCK SNPs (rs1801260, rs3749474, rs4580704) and the study procedures were performed in 897 patients from the CORDIOPREV clinical trial. After 12 months of intervention, we found significant gene–diet interactions between rs4580704 SNP and the LF diet. Specifically, major allele carriers C/C displayed a greater decrease in high sensitivity C‐reactive protein (p < 0.001) and a significant increase in HDL/apolipoprotein A1 ratio (p = 0.029) than minor G allele carriers (G/G + C/G). No other gene–diet interactions were observed in this research.
Conclusion
These results suggest that rs4580704 SNP interacts with the LF diet improving inflammation status and dyslipidemia related with CHD. The shift toward “personalized nutrition” based on gene–nutrient interactions may be suitable for promoting cardiovascular health in patients with CHD.
Circulating microRNAs (miRNAs) have been proposed as biomarkers for type 2 diabetes (T2D). Adipose tissue (AT), for which dysfunction is widely associated with T2D development, has been reported as a ...major source of circulating miRNAs. However, the role of dysfunctional AT in the altered pattern of circulating miRNAs associated with T2D onset remains unexplored. Herein, we investigated the relationship between T2D-associated circulating miRNAs and AT function, as well as the role of preadipocytes and adipocytes as secreting cells of candidate circulating miRNAs. Among the plasma miRNAs related to T2D onset in the CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) cohort, baseline miR-223-3p levels (diminished in patients who next developed T2D incident-T2D) were significantly related to AT insulin resistance (IR). Baseline serum from incident-T2D participants induced inflammation and IR in 3T3-L1 adipocytes. We demonstrated that tumor necrosis factor (TNF)-α inhibited miR-223-3p secretion while enhancing miR-223-3p intracellular accumulation in 3T3-L1 (pre)adipocytes. Overexpression studies showed that an intracellular increase of miR-223-3p impaired glucose and lipid metabolism in these cells. Our findings provide mechanistic insights into the alteration of circulating miRNAs preceding T2D, unveiling both preadipocytes and adipocytes as miR-223-3p-secreting cells and suggesting that inflammation promotes miR-223-3p intracellular accumulation, which might contribute to (pre)adipocyte dysfunction and body metabolic dysregulation.
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The relationship between adipose dysfunction and circulating miRNAs associated with T2D onset was investigated. Low circulating miR-223-3p related to adipose tissue insulin resistance index (ATIRI) in incident-T2D subjects. Both preadipocytes and adipocytes secrete miR-223-3p, and inflammation-induced intracellular miR-223-3p accumulation leads to cell dysfunction, which might contribute to body metabolic dysregulation.
SCOPE: To examine whether the consumption of a Mediterranean diet (MedDiet), compared with a low‐fat diet, interacts with two single nucleotide polymorphisms at the tumor necrosis factor alpha gene ...(rs1800629, rs1799964) in order to improve triglycerides (TG), glycemic control, and inflammation markers. METHODS AND RESULTS: Genotyping, biochemical measurements, dietary intervention, and oral fat load test meal were determined in 507 metabolic syndrome (MetS) patients selected from all the subjects included in CORDIOPREV clinical trial (n = 1002). At baseline, G/G subjects (n = 408) at the rs1800629 polymorphism, showed higher fasting and postprandial TG (p = 0.003 and p = 0.025, respectively), and high sensitivity C‐reactive protein (hsCRP) (p = 0.003) plasma concentrations than carriers of the minor A‐allele (G/A + A/A) (n = 99). After 12 months of MedDiet, baseline differences between genotypes disappeared. The decrease in TG and hsCRP was statistically significant in G/G subjects (n = 203) compared with carriers of the minor A‐allele (p = 0.005 and p = 0.034, respectively) (n = 48). No other gene–diet interactions were observed in either diet. CONCLUSION: These results suggest that the rs1800629 at the tumor necrosis factor alpha gene interacts with MedDiet to influence TG metabolism and inflammation status in MetS subjects. Understanding the role of gene–diet interactions may be the best strategy for personalized treatment of MetS.
MicroRNAs (miRNAs) regulate the expression of genes associated with the development of diseases, including type 2 diabetes mellitus (T2DM). However, the use of miRNAs to predict T2DM remission has ...been poorly studied. Therefore, we aimed to investigate whether circulating miRNAs could be used to predict the probability of T2DM remission in patients with coronary heart disease. We included the newly diagnosed T2DM (n = 190) of the 1,002 patients from the CORDIOPREV study. Seventy-three patients reverted from T2DM after 5 years of dietary intervention with a low-fat or Mediterranean diet. Plasma levels of 56 miRNAs were measured by OpenArray. Generalized linear model, receiver operating characteristic (ROC), Cox regression, and pathway analyses were performed. ROC analysis based on clinical variables showed an area under the curve (AUC) of 0.66. After a linear regression analysis, seven miRNAs were identified as the most important variables in the group’s differentiation. The addition of these miRNAs to clinical variables showed an AUC of 0.79. Cox regression analysis using a T2DM remission score including miRNAs showed that high-score patients have a higher probability of T2DM remission (hazard ratio HRlow versus high, 4.44). Finally, 26 genes involved in 10 pathways were related to the miRNAs. We have identified miRNAs (hsa-let-7b, hsa-miR-101, hsa-miR-130b-3p, hsa-miR-27a, hsa-miR-30a-5p, hsa-miR-375, and hsa-miR-486) that contribute to the prediction of T2DM remission in patients with coronary heart disease.
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Type 2 diabetes mellitus (T2DM) is one of the most important health problems worldwide, but this disease may revert by the consumption of healthy diets. Our work suggests the use of seven genetic factors (microRNAs) to predict the probability of T2DM remission in patients with coronary heart disease.
Leukocyte telomere length (LTL) attrition has been associated with age-related diseases. Telomerase RNA Component (TERC) genetic variants have been associated with LTL; whereas fatty acids (FAs) can ...interact with genetic factors and influence in aging. We explore whether variability at the TERC gene locus interacts with FA profile and two healthy diets (low-fat diet vs Mediterranean diet MedDiet) modulating LTL, glucose metabolism, and inflammation status in coronary heart disease (CHD) patients.
Inflammation status (high-sensitivity C-reactive protein hsCRP, glucose metabolism-glucose, insulin, and glycated hemoglobin HbA1c, and homeostasis model assessment of insulin resistance HOMA-IR), LTL, FAs, and single nucleotide polymorphisms (SNPs) of the TERC gene (rs12696304, rs16847897, and rs3772190) were determined in 1,002 patients from the CORDIOPREV study (NCT00924937).
We report an interaction of the TERC rs12696304 SNP with monounsaturated fatty acid (MUFA) affecting LTL (p interaction = .01) and hsCRP (p interaction = .03). Among individuals with MUFA levels above the median, CC individuals showed higher LTL and lower hsCRP than G-allele carriers. Moreover, MedDiet interacted with TERC rs12696304 SNP (p interaction = .03). Specifically, CC individuals displayed a greater decrease in hsCRP than G-allele carriers. These results were not adjusted for multiple statistical testing and p less than .05 was considered significant.
Our findings suggest that the TERC rs12696304 SNP interacts with MUFA improving inflammation status and telomere attrition related with CHD. Moreover, the MedDiet intervention improves the inflammatory profile in CC individuals compared with the G-allele carriers. These interactions could provide a right strategy for personalized nutrition in CHD patients.
Purpose
The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. For this reason, it is essential to identify biomarkers for the early detection of T2DM risk and/or for a better ...prognosis of T2DM. We aimed to identify a plasma fatty acid (FA) profile associated with T2DM development.
Methods
We included 462 coronary heart disease patients from the CORDIOPREV study without T2DM at baseline. Of these, 107 patients developed T2DM according to the American Diabetes Association (ADA) diagnosis criteria after a median follow-up of 60 months. We performed a random classification of patients in a training set, used to build a FA Score, and a Validation set, in which we tested the FA Score.
Results
FA selection with the highest prediction power was performed by random survival forest in the Training set, which yielded 4 out of the 24 FA: myristic, petroselinic, α-linolenic and arachidonic acids. We built a FA Score with the selected FA and observed that patients with a higher score presented a greater risk of T2DM development, with an HR of 3.15 (95% CI 2.04–3.37) in the Training set, and an HR of 2.14 (95% CI 1.50–2.84) in the Validation set, per standard deviation (SD) increase. Moreover, patients with a higher FA Score presented lower insulin sensitivity and higher hepatic insulin resistance (
p
< 0.05).
Conclusion
Our results suggest that a detrimental FA plasma profile precedes the development of T2DM in patients with coronary heart disease, and that this FA profile can, therefore, be used as a predictive biomarker.
Clinical Trials.gov.Identifier
NCT00924937.
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