Poor prognosis indicators of type-2 diabetic COVID-19 patients.

Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM+) and non-diabetic (DM-) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM+ and DM- groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM+ COVID-19 patients. We found a poorer prognosis for the DM+ COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM- group. DM+ COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM- patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.

Poor prognosis indicators of type-2 diabetic COVID-19 patients

Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM+) and non-diabetic (DM-) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM+ and DM- groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM+ COVID-19 patients. We found a poorer prognosis for the DM+ COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM- group. DM+ COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM- patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.

Genome-wide analysis in 756,646 individuals provides first genetic evidence that ACE2 expression influences COVID-19 risk and yields genetic risk scores predictive of severe disease.

SARS-CoV-2 enters host cells by binding angiotensin-converting enzyme 2 (ACE2). Through a genome-wide association study, we show that a rare variant (MAF = 0.3%, odds ratio 0.60, P=4.5×10-13) that down-regulates ACE2 expression reduces risk of COVID-19 disease, providing human genetics support for the hypothesis that ACE2 levels influence COVID-19 risk. Further, we show that common genetic variants define a risk score that predicts severe disease among COVID-19 cases.

DNA methylation pattern changes following a short-term hypocaloric diet in women with obesity.

BACKGROUND/OBJECTIVES: We aimed to investigate the effects of short-term hypocaloric diet-induced weight loss on DNA methylation profile in leukocytes from women with severe obesity. METHODS: Eleven women with morbid obesity (age: 36.9 ± 10.3 years; BMI: 58.5 ± 10.5 kg/m2) were assessed before and after 6 weeks of a hypocaloric dietary intervention. The participants were compared with women of average weight and the same age (age: 36.9 ± 11.8 years; BMI: 22.5 ± 1.6 kg/m2). Genome-wide DNA methylation analysis was performed in DNA extracted from peripheral blood leukocytes using the Infinium Human Methylation 450 BeadChip assay. Changes (Δß) in the methylation level of each CpGs were calculated. A threshold with a minimum value of 10%, p < 0.001, for the significant CpG sites based on Δß and a false discovery rate of <0.05 was set. RESULTS: Dietary intervention changed the methylation levels at 16,064 CpG sites. These CpGs sites were related to cancer, cell cycle-related, MAPK, Rap1, and Ras signaling pathways. However, regardless of hypocaloric intervention, a group of 878 CpGs (related to 649 genes) remained significantly altered in obese women when compared with normal-weight women. Pathway enrichment analysis identified genes related to the cadherin and Wnt pathway, angiogenesis signaling, and p53 pathways by glucose deprivation. CONCLUSION: A short-term hypocaloric intervention in patients with severe obesity partially restored the obesity-related DNA methylation pattern. Thus, the full change of obesity-related DNA methylation patterns could be proportional to the weight-loss rate in these patients after dietary interventions.

Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients.

Clopidogrel and aspirin are the most commonly used medications worldwide for dual antiplatelet therapy after percutaneous coronary intervention. However, clopidogrel hyporesponsiveness related to gene polymorphisms is a concern. Populations with higher degrees of genetic admixture may have increased prevalence of clopidogrel hyporesponsiveness. To assess this, we genotyped CYP2C19, ABCB1, and PON1 in 187 patients who underwent percutaneous coronary intervention. Race was self-defined by patients. We also performed light transmission aggregometry with adenosine diphosphate (ADP) and arachidonic acid during dual antiplatelet therapy. We found a significant difference for presence of the CYP2C19*2 polymorphism between white and non-white patients. Although 7% of patients had platelet resistance to clopidogrel, this did not correlate with any of the tested genetic polymorphisms. We did not find platelet resistance to aspirin in this cohort. Multivariate analysis showed that patients with PON1 and CYP2C19 polymorphisms had higher light transmission after ADP aggregometry than patients with native alleles. There was no preponderance of any race in patients with higher light transmission aggregometry. In brief, PON1 and CYP2C19 polymorphisms were associated with lower clopidogrel responsiveness in this sample. Despite differences in CYP2C19 polymorphisms across white and non-white patients, genetic admixture by itself was not able to identify clopidogrel hyporesponsiveness.

UCP2 expression is associated with weight loss after hypocaloric diet intervention.

BACKGROUND/OBJECTIVES: Although energy restriction contributes to weight loss, it may also reduce energy expenditure, limiting the success of weight loss in the long term. Studies have described how genetics contributes to the development of obesity, and uncoupling proteins 1 and 2 (UCP1 and UCP2) and beta-3-adrenoceptor (ADRB3) have been implicated in the metabolic pathways that culminate in this condition. This study aimed to evaluate how the UCP1, UCP2 and ADRB3 genes influence weight loss in severely obese women submitted to hypocaloric dietary intervention. SUBJECTS/METHODS: This longitudinal study included 21 women divided into two groups: Group 1 (Dietary intervention (G1)) consisted of 11 individuals with severe obesity (body mass index (BMI) ⩾40 kg/m2), selected for dietary intervention and Group 2 (Control (G2)) consisted of 10 normal-weight women (BMI between 18.5 and 24.9 kg/m2). Evaluation included weight (kg), height (m), waist circumference (cm), body composition, resting metabolic rate (RMR, kcal) and abdominal subcutaneous adipose tissue collection. The dietary intervention required that G1 patients remained hospitalized in the university hospital for 6 weeks receiving a hypocaloric diet (1200 kcal per day). The statistical analyses included t-test for paired samples, Spearman correlation and multivariate linear regressions, with the level of significance set at P<0.05. RESULTS: Weight (155.0±31.4-146.5±27.8 kg), BMI (58.5±10.5-55.3±9.2 kg/m2), fat-free mass (65.4±8.6-63.1±7.1 kg), fat mass (89.5±23.0-83.4±21.0 kg) and RMR (2511.6±386.1-2324.0±416.4 kcal per day) decreased significantly after dietary intervention. Multiple regression analyses showed that UCP2 expression contributed to weight loss after dietary intervention (P=0.05). CONCLUSIONS: UCP2 expression is associated with weight loss after hypocaloric diet intervention.

Role of UCP2 polymorphisms on dietary intake of obese patients who underwent bariatric surgery.

Uncoupling protein 2 ( UCP2 ) plays an important role in body weight and energy metabolism and may be related to the control of food consumption. This study aimed to investigate the contribution of UCP2 gene variants on the dietary intake on a population after bariatric surgery. This study enrolled 150 obese patients (body mass index ≥ 35kg m(-2) ) who submitted to Roux-en-Y gastric bypass. Weight (kg), BMI (kg m(-2) ), energy (kcal d(-1) ) and macronutrients intake (g d(-1) ) of preoperative and 1-year postoperative period were collected from medical records. Ala55Val and -866G>A polymorphisms in the UCP2 gene were genotyped through allelic discrimination method in real-time polymerase chain reaction using the TaqMan pre-designed SNP Genotyping Assays kits. Hardy-Weinberg equilibrium, t-test and regression models were performed in statistical analysis (P<0.05).We found an allelic frequency of 0.44 for allele Val and 0.41 for allele A. In the postoperative period, patients with at least one rare allele for polymorphisms and with at least one rare allele for both polymorphisms together (haplotype) present a greater energy and carbohydrate intake, even after adjusting for gender, age and weight. Genetic variants in UCP2 gene were associated with the dietary consumption after Roux-En-Y gastric bypass.

Zinc pharmacokinetic parameters in the determination of body zinc status in children.

BACKGROUND/OBJECTIVES: Serum or tissue zinc concentrations are often used to assess body zinc status. However, all of these methods are relatively inaccurate. Thus, we investigated three different kinetic methods for the determination of zinc clearance to establish which of these could detect small changes in the body zinc status of children. SUBJECTS/METHODS: Forty apparently healthy children were studied. Renal handling of zinc was investigated during intravenous zinc administration (0.06537 mg Zn/kg of body weight), both before and after oral zinc supplementation (5 mg Zn/day for 3 months). Three kinetic methods were used to determine zinc clearance: CZn-Formula A and CZn-Formula B were both used to calculate systemic clearance; the first is a general formula and the second is used for the specific analysis of a single-compartment model; CZn-Formula C is widely used in medical practices to analyze kinetic routine. RESULTS: Basal serum zinc values, which were within the reference range for healthy children, increased significantly after oral zinc supplementation. The three formulas used gave different results for zinc clearance both before and after oral zinc supplementation. CZn-Formula B showed a positive correlation with basal serum zinc concentration after oral supplementation (R2=0.1172, P=0.0306). In addition, CZn-Formula B (P=0.0002) was more effective than CZn-Formula A (P=0.6028) and CZn-Formula C (P=0.0732) in detecting small variations in body zinc status. CONCLUSIONS: All three of the formulas used are suitable for studying zinc kinetics; however, CZn-Formula B is particularly effective at detecting small changes in body zinc status in healthy children.

A common biological basis of obesity and nicotine addiction.

Smoking influences body weight such that smokers weigh less than non-smokers and smoking cessation often leads to weight increase. The relationship between body weight and smoking is partly explained by the effect of nicotine on appetite and metabolism. However, the brain reward system is involved in the control of the intake of both food and tobacco. We evaluated the effect of single-nucleotide polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and tested the 32 SNPs identified in a meta-analysis for association with two smoking phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day (CPD) in an Icelandic sample (N=34,216 smokers). Combined according to their effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD (r=0.032, P=8.0 × 10(-7)). These findings replicate in a second large data set (N=127,274, thereof 76,242 smokers) for both SI (P=1.2 × 10(-5)) and CPD (P=9.3 × 10(-5)). Notably, the variant most strongly associated with BMI (rs1558902-A in FTO) did not associate with smoking behavior. The association with smoking behavior is not due to the effect of the SNPs on BMI. Our results strongly point to a common biological basis of the regulation of our appetite for tobacco and food, and thus the vulnerability to nicotine addiction and obesity.

Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease affecting the joints. A heterogeneous response to available therapies demonstrates the need to identify those patients likely to benefit from a particular therapy. Our objective was to identify genetic factors associated with response to tocilizumab, a humanized monoclonal antibody targeting the interleukin (IL)-6 receptor, recently approved for treating RA. We report the first genome-wide association study on the response to tocilizumab in 1683 subjects with RA from six clinical studies. Putative associations were identified with eight loci, previously unrecognized as linked to the IL-6 pathway or associated with RA risk. This study suggests that it is unlikely that a major genetic determinant of response exists, and it illustrates the complexity of performing genome-wide association scans in clinical trials.

Analysis of bone microarchitecture related to anthropometry in climateric women.

BACKGROUND: Osteoporosis is one of the most important public health problems involving a high percentage of costs in the medical care system. Reliable diagnostic techniques for an early detection of bone deterioration and studies of factors that influence its development in menopausal women are crucial. The aim of the study was to determine the relationship between bone microarchitecture and anthropometry in climacteric women. METHODS: Women were recruited at the Menopause Clinic, University Hospital of FMRP/USP, and submitted to anthropometry and to the evaluation of bone quality (Ultrasound Bone Profile Index, UBPI) and quantity (Amplitudedependent Speed of Sound, AD-SoS-) by phalangeal quantitative osteosonography (DBM Sonic BP). Descriptive analysis of the data was reported and a multiple linear regression was performed using the software SAS® 9.0. RESULTS: 71 patients aged 58 ± 7 y were studied: 28% had BMI 18.5-24.9 kg/m(2), 35% BMI 24.9-29.9 and 37% BMI > 30. Mean AD-SoS was 2059 ± 79 m/s and mean UBPI was 0.67 ± 0.13. Considering AD-SoS the dependent variable, there was no statistically significant relationship between age (p = 0.20), BMI (p = 0.76), fat mass by bioelectrical impedance (p = 0.42) and by anthropometry (p = 0.95). The variables had very low effect on the UBPI when it was considered the dependent variable. CONCLUSIONS: The relation between bone microarchitecture and the anthropometry of the women studied shows that, the greater the bone quantity, the better the anthropometric parameters, without statistically significance. This work was a cross-sectional study on a small sample that needs to be validated in a prospective design.

Bioelectrical impedance with different equations versus deuterium oxide dilution method for the inference of body composition in healthy older persons.

BACKGROUND: There is no consensus regarding the accuracy of bioimpedance for the determination of body composition in older persons. OBJECTIVE: This study aimed to compare the assessment of lean body mass of healthy older volunteers obtained by the deuterium dilution method (reference) with those obtained by two frequently used bioelectrical impedance formulas and one formula specifically developed for a Latin-American population. DESIGN: A cross-sectional study. PARTICIPANTS: Twenty one volunteers were studied, 12 women, with mean age 72±6.7 years. SETTING: Urban community, Ribeirão Preto, Brazil. MEASUREMENT: Fat free mass was determined, simultaneously, by the deuterium dilution method and bioelectrical impedance; results were compared. In bioelectrical impedance, body composition was calculated by the formulas of Deuremberg, Lukaski and Bolonchuck and Valencia et al. RESULTS: Lean body mass of the studied volunteers, as determined by bioelectrical impedance was 37.8±9.2 kg by the application of the Lukaski e Bolonchuk formula, 37.4±9.3 kg (Deuremberg) and 43.2±8.9 kg (Valencia et. al.). The results were significantly correlated to those obtained by the deuterium dilution method (41.6±9.3 Kg), with r=0.963, 0.932 and 0.971, respectively. Lean body mass obtained by the Valencia formula was the most accurate. CONCLUSION: In this study, lean body mass of older persons obtained by the bioelectrical impedance method showed good correlation with the values obtained by the deuterium dilution method. The formula of Valencia et al., developed for a Latin-American population, showed the best accuracy.

Lean and fat mass loss in obese patients before and after Roux-en-Y gastric bypass: a new application for ultrasound technique.

OBJECTIVE: This study aims to evaluate the thickness of the femoral quadriceps and biceps brachii and brachialis muscles bilaterally and the adjacent subcutaneous fat in patients undergoing gastric bypass Roux-en-Y before and after surgery, using ultrasound as the diagnostic method of choice. METHODS: We studied 12 patients undergoing this surgical method preoperatively and during the first, third, and sixth postoperative months. During these periods, patients were evaluated by ultrasound to determine the thickness of subcutaneous adipose tissue and muscle of the upper and lower limbs. RESULTS: Postoperatively, these patients showed a reduction in the thickness of the upper and lower extremities muscle and adipose tissue as compared to their preoperative values. There was a significant difference in the loss of muscle thickness in all postoperative months and in the thickness of fatty tissue in the sixth month after surgery, compared to the preoperative muscle and fatty tissue thickness. CONCLUSIONS: Ultrasound can be considered as the diagnostic method of choice when assessment of the fat and lean body mass is required in morbidly obese patients before and after bariatric surgery.

Iron-Fortified Drinking Water Studies for the Prevention of Children's Anemia in Developing Countries.

Anemia and iron deficiency should receive special attention considering their high prevalence and serious consequences. For prevention, globally it is recommended to increase dietary iron intake, iron fortification of industrialized foods, and medical iron supplementation. Food fortification for the prevention of iron deficiency in developing countries should consider carriers locally available and consumed daily, requiring limited infrastructure and technology. Drinking water is the iron carrier we have been working for years for the prevention of iron deficiency and anemia in small children in Brazil. It was shown that studies with iron-fortified drinking water were proved to be effective on children's anemia prevention. Water is found everywhere, consumed daily by everyone may be easily fortified with simple technology, is low priced and was effective on the prevention of children's anemia. Fortification of drinking water with iron was locally implemented with the direct participation of the government and community. Government authorities, health personnel and population were part of the project and responsible for its community implementation. The mayor/municipality permitted and supported the proposal to supply it to children at their day-care centers. To keep the children drinking water iron fortified supply an officially authorized legislation was also approved.

Body composition assessment of undernourished older subjects by dual-energy x-ray absorptiometry and bioelectric impedance analysis.

BACKGROUND: The prevention and treatment of diseases related to changes in body composition require accurate methods for the measurement of body composition. However, few studies have dealt specifically with the assessment of body composition of undernourished older subjects by different methodologies. OBJECTIVES: To assess the body composition of undernourished older subjects by two different methods, dual energy x-ray absorptiometry (DXA) and bioelectric impedance (BIA), and to compare results with those of an eutrophic group. DESIGN: The study model was cross-sectional; the study was performed at the University Hospital of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil. PARTICIPANTS: Forty-one male volunteers aged 62 to 91 years. The groups were selected on the basis of anamnesis, physical examination and nutritional assessment according to the Mini Nutritional Assessment (MNA) score. Body composition was assessed by DXA and BIA. RESULTS: Body weight, arm and calf circumference, body mass index (BMI), fat free mass (FFM) and fat mass (FM) were significantly lower in the undernourished group as compared to the eutrophic group. There were no significant differences between FFM and FM mean values determined by DXA and BIA in both groups, but the agreement between methods in the undernourished group was less strong. CONCLUSION: Our results suggest caution when BIA is to be applied in studies including undernourished older subjects. This study does not support BIA as an accurate method for the individual assessment of body composition.

What is the best equation to estimate the basal energy expenditure of climacteric women?

OBJECTIVES: The methods currently available for the measurement of energy expenditure in patients, such as indirect calorimetry and double-labelled water, are expensive and are limited in Brazil to research projects. Thus, equations for the prediction of resting metabolic rate appear to be a viable alternative for clinical practice. However, there are no specific equations for the Brazilian population and few studies have been conducted on Brazilian women in the climacteric period using existing and commonly applied equations. On this basis, the objective of the present study was to investigate the concordance between the predictive equations most frequently used and indirect calorimetry for the measurement of resting metabolic rate. METHODS: We calculated the St. Laurent concordance correlation coefficient between the equations and resting metabolic rate calculated by indirect calorimetry in 46 climacteric women. RESULTS: The equation showing the best concordance was that of the FAO/WHO/UNU formula (0.63), which proved to be better than the Harris & Benedict equation (0.55) for the sample studied. CONCLUSIONS: On the basis of the results of the present study, we conclude that the FAO/WHO/UNU formula can be used to predict better the resting metabolic rate of climacteric women. Further studies using more homogeneous and larger samples are needed to permit the use of the FAO/WHO/UNU formula for this population group with greater accuracy.

Influence of insulin treatment on the lacrimal gland and ocular surface of diabetic rats.

Previous studies have observed changes in the lacrimal gland and ocular surface related to diabetes mellitus and related it to insulin resistance or insufficiency and oxidative damage. The aim of this study was to evaluate whether insulin treatment inhibits those changes. Diabetes was induced in male Wistar rats with a single intravenous injection of streptozotocin and a subgroup was treated with insulin. After 5 and 10 weeks, the three groups (n = 5-10/group/experimental procedure) were compared for biochemical, functional, and histological parameters. After 5 weeks, changes in morphology and increased numbers of lipofucsin-like inclusions were observed in lacrimal glands of diabetic but not insulin-treated rats. After 5 weeks, malonaldehyde and total peroxidase activity were significantly higher in diabetic rats, but similar to control in insulin-treated diabetic rats (P = 0.03, P = 0.02, respectively). Our data indicate that diabetes induces histological alterations in lacrimal gland and suggests that hyperglycemia-related oxidative stress may participate in diabetic dry eye syndrome. Prevention by insulin replacement suggests direct hormone action and/or benefit by early sub optimal metabolic control.

Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2.

We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia.

Climacteric, physically active women ingesting their routine diet oxidize more carbohydrates than lipids.

OBJECTIVE: To investigate the influence of a routine Brazilian diet on the rate of oxidation of energy substrates in climacteric, obese women, who came to the outpatient clinic of the Hospital of the School of Medicine of Ribeirao Preto (HCFMRP-USP). METHODS: Subjects were recruited from outpatients at the Climacteric Clinic of the HCFMRP-USP, who were aged between 39 and 65 years and who voluntarily agreed to participate in this study. They were submitted to anthropometric measurements and indirect calorimetry for resting energy expenditure and substrate oxidation rate determination. RESULTS: The carbohydrate oxidation in the group of climacteric, obese women showed a significant positive correlation between energy consumption at rest and ingestion of carbohydrates (in grams); the subjects' rate of lipid intake showed a significant negative correlation with their body mass index, waist circumference, and daily total caloric intake. CONCLUSION: Carbohydrate intake and carbohydrate oxidation rate may contribute to weight gain in climacteric women.