Alterations in circulating levels of vitamin D binding protein, total and bioavailability of vitamin D in diabetic retinopathy patients.

AIMS: This study aimed to investigate the association between circulating levels of vitamin D binding protein (VDBP) and its genotypes and diabetic retinopathy risk. METHODS: This case-control study recruited 154 patients with type 2 diabetes mellitus; 62 with diabetic retinopathy (DR) and 92 without DR and diabetic nephropathy (DN). Circulating levels of 25-hydroxyvitamin D3 and VDBP levels were measured in the patients. The genotype and phenotype of VDBP were evaluated based on two common VDBP variations; rs7041 and rs4588. RESULTS: Serum levels of VDBP were significantly lower in patients with DR than in patients without DR and/or DN (Ln-VDBP (µg/ml): 6.14 ± 0.92 vs. 6.73 ± 1.45, p = 0.001) even after adjustment for age, sex, body mass index, disease duration, estimated glomerular filtration rate (eGFR), HbA1C, insulin therapy profile, and serum levels of 25(OH)D. The distribution of VDBP phenotypes and genotypes in the two studied groups were nearly the same, and the distribution was similar to that of the general population. CONCLUSIONS: In this study, we found the association between lower circulating levels of VDBP and risk of DR. However, the precise mechanism linking these two remains unknown. Further and more in-depth research is needed to find out the underlying causes of the relationship.

The lower basal metabolic rate is associated with increased risk of osteosarcopenia in postmenopausal women.

BACKGROUND: The goal of this study is to clarify clinical, functional, and biochemical features of postmenopausal women who are at risk of developing osteosarcopenia. METHODS: This is a cross-sectional study undertaken to investigate the co-accordance of osteoporosis and sarcopenia and common risk factors on 305 postmenopausal Iranian women. Sarcopenia and osteoporosis were defined based on the European Working Group on sarcopenia in Older People guidelines and WHO criteria, respectively. Confounding factors including age, menopausal age, obesity, sun exposure, physical activity, macronutrient composition, and calcium and vitamin D supplementations were considered for all participants. A multivariate model was used to consider the common risk factors of both disorders; osteoporosis and sarcopenia. RESULTS: The mean age was 57.9 years ± 6.0 SD (range: 48-78 years) and 37.4% of patients were 60 years or older. Among all participants, 35.7% were obese (BMI ≥ 30 kg/m2). Approximately 45% of all the study population had insufficient physical activity and at least half of participants had insufficient intake of protein. There was a significant correlation between bone density and muscle mass and basal metabolic rate (BMR) (p < 0.01). In multivariate-multivariable regression model, after Bonferroni correction for obesity, lower BMR was the only one associated with both lower muscle mass and bone density in lumbar and hip sites (p < 0.007). CONCLUSIONS: Our data suggest that low BMR might be an early predictor for concordance of osteoporosis and sarcopenia in postmenopausal women.

Bone mineral density and muscle mass in adults with developmental skeletal discrepancies.

BACKGROUND: It was aimed to investigate the musculoskeletal status in individuals diagnosed with skeletal discrepancies. METHODS: This case-control study was performed on 35 patients with developmental skeletal discrepancies listed for orthognathic surgery as a case group and 33 patients who were nominated for wisdom tooth removal as a control group. All participants were aged 18-40 years and the research was carried out in the period between May 2018 and May 2019. Dual X-ray absorptiometry (DEXA) was used to assess bone mass density at three bone sites: total hip, femoral neck, and the spinal lumbar vertebrae (L1-L4). The appendicular muscle mass index (ASMI) was measured based on the four limbs from the DEXA scan. RESULTS: Our data showed that 45.7% (16) of the case group were osteopenic or osteoporotic while in the control group only 21.2% (7) were osteopenic in at least one region (total hip, femoral neck, or lumbar) (p-value = 0.03). Regarding muscle mass, there was significantly lower SMI in subjects with skeletal discrepancies (case group) compared with the control group (median (IQR) 5.9 (2.5) vs. 6.8 (2.9) (kg/m2), respectively, p = 0.04). CONCLUSIONS: There is an essential need for more studies to understand the exact interrelationship between musculoskeletal status and skeletal jaw discrepancies.

Reduction in circulating vitamin D binding protein in patients with multiple sclerosis.

BACKGROUND: In this study, we aimed to determine the risk association between vitamin D binding protein (VDBP) polymorphism in patients with multiple sclerosis (MS) in a MS biobank and the difference in VDBP serum levels in MS patients who were recently diagnosed. METHOD: The current case-control study was performed on 296 MS patients and 313 controls. Thereafter, two common missense VDBP polymorphisms, named rs7041and rs4588, were evaluated in all the participants. Serum levels of vitamin D and vitamin D binding protein were assessed in 77 MS patients who were diagnosed since one year ago and in 67 healthy people who were matched in terms of age and sex. RESULT: The frequency distributions of VDBP genotypes and alleles of SNP rs7041 and rs4588 were observed to be similar in both the MS and control groups (p > 0.05). The VDBP haplotypes, as Gc2/Gc2, Gc1/Gc1, and Gc1/Gc2, were found to be similar in the MS and control groups (p > 0.05). In subgroup analysis, circulating VDBP was lower in MS patients (Ln-VDBP (µgr/ml): 3.64 ± 0.91 vs. 5.31 ± 0.77, p = 0.0001) even after adjusting for vitamin D levels, body mass index, and taking vitamin D supplement. There was no significant association between VDBP haplotypes and vitamin D levels in the two groups. CONCLUSION: The present study suggested an association between lower levels of circulating VDBP and multiple sclerosis in newly diagnosed patients. However, the VDBP causative role in the development of MS is still unclear, so it needs more studies.

The possible role of Interleukin-6 as a regulator of insulin sensitivity in patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is associated with inflammatory mediators that may also trigger downstream signaling pathways leading to reduce insulin sensitivity. METHODS: We aimed to determine the risk association of hyperinsulinemia in NMOSD patients with seropositive AQP4-IgG and the serum levels of interleukin (IL)-6 and IL-17A compared with the control group. Serum levels of metabolic (Insulin, Fasting Blood Sugar (FBS), lipid profile) and inflammatory (IL-6 and IL-17) markers were assessed in 56 NMOSD patients and 100 controls. RESULTS: Hyperinsulinemia was more prevalent in NMOSD patients independent of age, sex and body mass index (BMI) (48.2% vs. 26%, p = 0.005) compared to control group. After adjusting age, sex and BMI, there was significant association between lower insulin sensitivity (IS) and NMOSD risk (95% CI: Beta = 0.73, 0.62 to 0.86, p = 0.0001). Circulating levels of IL-6 and IL-17 were higher in NMOSD patients, and only IL-6 had an effect modifier for the association between lower insulin sensitivity and NMOSD risk. CONCLUSIONS: Our data suggests that inflammatory pathogenesis of NMOSD leads to hyperinsulinemia and increases the risk of insulin resistance.

Treatment With 25-Hydroxyvitamin D3 (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter, Randomized, Placebo-Controlled, Double-Blinded Clinical Trial.

OBJECTIVE: The goal of this randomized, double-blinded, placebo-controlled clinical trial was to investigate the therapeutic efficacy of oral 25-hydroxyvitamin D3 (25(OH)D3) in improving vitamin D status in vitamin D-deficient/vitamin D-insufficient patients infected with the SARS-CoV-2 (COVID-19) virus. METHODS: This is a multicenter, randomized, double-blinded, placebo-controlled clinical trial. Participants were recruited from 3 hospitals that are affiliated to [Institution Blinded for Review] and [Institution Blinded for Review]. RESULTS: A total 106 hospitalized patients who had a circulating 25(OH)D3 concentration of <30 ng/mL were enrolled in this study. Within 30 and 60 days, 76.4% (26 of 34) and 100% (24 of 24) of the patients who received 25(OH)D3 had a sufficient circulating 25(OH)D3 concentration, whereas ≤12.5% of the patients in the placebo group had a sufficient circulating 25(OH)D3 concentration during the 2-month follow-up. We observed an overall lower trend for hospitalization, intensive care unit duration, need for ventilator assistance, and mortality in the 25(OH)D3 group compared with that in the placebo group, but differences were not statistically significant. Treatment with oral 25(OH)D3 was associated with a significant increase in the lymphocyte percentage and decrease in the neutrophil-to-lymphocyte ratio in the patients. The lower neutrophil-to-lymphocyte ratio was significantly associated with reduced intensive care unit admission days and mortality. CONCLUSION: Our analysis indicated that oral 25(OH)D3 was able to correct vitamin D deficiency/insufficiency in patients with COVID-19 that resulted in improved immune function by increasing blood lymphocyte percentage. Randomized controlled trials with a larger sample size and higher dose of 25(OH)D3 may be needed to confirm the potential effect of 25(OH)D3 on reducing clinical outcomes in patients with COVID-19.

Dietary patterns interact with chromosome 9p21 rs1333048 polymorphism on the risk of obesity and cardiovascular risk factors in apparently healthy Tehrani adults.

PURPOSE: Gene-dietary patterns may contribute to determining body composition and related biochemical indices. The aim of this study was to evaluate interactions between rs1333048 polymorphism and major dietary patterns on body fat percentage, general and central obesity, and related biochemical measurements. METHODS: This cross-sectional study was conducted on 265 healthy Tehrani adults with mean age of 35 years (47.5% men, 52.5% women). Dietary patterns (DPs) were extracted by factor analysis. Bioelectrical impedance analysis was used for body analysis and rs1333048 was genotyped by the restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Three DPs were extracted: restricted refined grains DP, legumes DP and healthy DP. AA genotype compared to CC genotype had greater odds for general obesity before (OR 3.14; 95% CI 1.008-9.60, P = 0.045) and after (OR 3.11; 95% CI 1.008-9.60, P = 0.048) adjusting for potential confounders. Individuals with AA genotype were more likely to be centrally obese before (OR 2.09; 95% CI 1.006-4.35, P = 0.048) and after (OR 2.63; 95% CI 1.12-6.17, P = 0.026) controlling for potential confounders. Significant interactions were observed between Legumes DP and rs1333048 SNP on waist circumference (P = 0.047), body fat % (BFP) (P = 0.048), hs-Crp (P = 0.042), BMI (P = 0.073), WHtR (P = 0.063) and odds for general obesity (P = 0.051). Following this DP reduced all these items for individuals with CC genotype, whereas increased them for people who carry CA or AA genotypes. CONCLUSIONS: The findings indicate that there are significant associations between AA genotype of rs1333048 SNP and general and central obesity, and significant interaction between alleles of this SNP and major dietary patterns on the odds of general obesity, BFP, waist circumference, BMI, WHtR and hs-Crp.

The Association between Vitamin D Deficiency and variants of Vitamin D Binding protein gene among Healthy Iranian Adults.

Background: The high prevalence of vitamin D deficiency may be due to both genetic and environment factors. The aim of this study was to demonstrate that vitamin D deficiency may be due to variants of vitamin D binding protein (DBP) among otherwise healthy Iranian adults. Methods: This cross-sectional study was conducted on 265 healthy adults in Tehran. Anthropometric and biochemical parameters were assessed. Dietary vitamin D intake was assessed with a Food Frequency Questionnaire (FFQ), and participant DBP genotypes were determined by polymerase chain reactions - restriction fragment length polymorphism. Results: Significant associations were found between vitamin D status and low-density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), and fasting blood sugar (P < 0.001), after adjustment for confounder factors. This study demonstrated that "rs7041" gene was associated with vitamin D deficiency (OR = 0.63, ß ± SE = -0.46 ± 0.14, P < 0.0001). After considering the "GG" genotype of the "rs7041" polymorphism as a reference, the prevalence of vitamin D deficiency was found to be higher in the individuals with "TT" genotype from the "rs7041" polymorphism. Conclusion: It was found that the prevalence of vitamin D deficiency was higher in individuals with T allele carriers in the "rs7041" polymorphism.

Possible association between circulating CTRP3 and knee osteoarthritis in postmenopausal women.

BACKGROUND: Osteoarthritis (OA) is considered as one of the most common cause of chronic pain and functional disabilities in the elderly. AIM: To examine serum levels of complement-C1q TNF-related protein 3 (CTRP3) in postmenopausal women with knee OA. METHODS: A population-based cross-sectional study was performed in women who complained of chronic knee pain. All subjects were followed by clinical and weight-bearing bilateral anteroposterior radiographical examinations. The Kellgren and Lawrence (K&L) score was used for knee OA classification. Two groups of postmenopausal women were chosen to investigate CTRP3 as an OA marker who had the K&L score ≥ 3 as a case group and K&L ≤ 1 as a control group. Serum levels of CTRP3 were measured in two groups. RESULTS: According to K&L classification, 36 subjects with knee OA and 54 age-matched without or mild OA were selected. After adjusting the obtained data for taking NSAID drugs, the concentration of Ln CTRP3 in serum of patients with OA was lower compared to control group [mean ± SE, (0.39 ± 0.05 ng/ml vs. 0.48 ± 0.03 ng/ml, respectively, p = 0.04)]. DISCUSSION: There is a possible role for CTRP3 as an anti-inflammatory mediator in knee OA in postmenopausal women. CONCLUSIONS: Our results indicate an association between CTRP3 and knee OA. However, a much more robust study is required to draw that circulating CTRP3 could be a clinical marker for osteoarthritis.

Effects of French maritime pine bark extract (Oligopin®) supplementation on bone remodeling markers in postmenopausal osteopenic women: A randomized clinical trial.

French maritime pine bark extract (FMPBE; Oligopin®), a dietary supplement, is rich in procyanidin. The objective of this study was to determine the effects of FMPBE on bone remodeling in postmenopausal osteopenic women. This randomized, double-blinded, placebo-controlled clinical trial was conducted on 40 postmenopausal osteopenic women. Individuals were randomly assigned to either FMPBE (250 mg/day, n = 21) or placebo (250-mg starch/day, n = 19) for 12 weeks. Biochemical indices, including bone remodeling marker, were assessed before and after the intervention. After the 12-week intervention, that is, FMPBE supplementation, a significant increase in bone alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP) levels and a significant decrease in C-terminal telopeptide of type I collagen (CTx1) were observed. Compared with the control group, FMPBE supplementation resulted in a significant increase in P1NP (0.015), BAP levels (0.001), and BAP/CTx1 ratio (p = 0.001) and a significant decrease in CTx1 levels (0.006). FMPBE supplementation for 12 weeks in postmenopausal osteopenic women produced favorable effects on bone markers. Meanwhile, further research is needed to determine whether FMPBE supplements can be used as a preventive strategy for bone loss in postmenopausal osteopenic women.

The Association Between Dietary Glycemic Index and Glycemic Load and a Body Shape and Fat Distribution Among Apparently Healthy Iranian Adults.

OBJECTIVE: The role of dietary glycemic index (GI) and glycemic load (GL) in the development of obesity has been debated globally. The relationship with body shape and fat distribution was examined in this cross-sectional association study among apparently healthy Iranian adults. METHODS AND MATERIALS: A study population of 265 (126 males and 139 females) aged 18-55 years participated in this cross-sectional study from the communities of Tehran based on cluster sampling. GI and GL were assessed by the 147-item food frequency questionnaire (FFQ) completed by a trained dietitian. Weight, height, waist circumference (WC), and hip circumference of the participants were measured, and body mass index (BMI), waist-to-hip ratio (WHR), and A Body Shape Index (ABSI) were further calculated. Fat mass and fat-free mass were also measured using a body composition analyzer, and fat mass index (FMI) and fat-free mass index (FFMI) were then calculated. Multivariate regression models were fitted to assess the association between GI/GL and fat distribution measures such as FMI, FFMI, WC, BMI, WHR, and ABSI, considering potential confounding factors such as sex, age, BMI, and physical activity. RESULTS: There was a statistically significant inverse association between GL and WC, BMI, and ABSI found in the adjusted model. GL was inversely associated with WC for both the adjusted model (p-trend = 0.027) and the crude model. Also, an inverse association was seen between GL and BMI (p-trend = 0.019) in the adjusted model but a marginal association in the crude model. GL was also inversely associated with ABSI (p-trend = 0.089) in the highest tertile. CONCLUSION: Dietary GL but not GI is inversely associated with fat distribution measures such as WC, BMI, and ABSI in the study population. This result may suggest a beneficial role of higher-GL diets in the prevention of obesity.

Dietary fat intake associated with bone mineral density among visfatin genotype in obese people.

Osteoporosis and adipose tissue are closely related with many contradictions. Visfatin is an adipokine that is related to osteoporosis and adiposity. This nutrigenomics study examined the interaction between visfatin genotypes and dietary fat intake, with regard to bone mineral density (BMD) among an obese population. In this cross-sectional study, 336 subjects were enrolled; the mean age was 38·25 (sd 11·69) years and the mean BMI was 31·79 (sd 4·77) kg/m2. Laboratory measurements were lipid profile, insulin and fasting blood sugar. Bone density measurements were assessed by dual-energy X-ray absorptiometry. Dietary data were collected through a 3-d 24-h dietary recall. Genotyping for visfatin gene SNP (rs2110385) was performed by the PCR-restriction fragment length polymorphism method. The frequency of GG, GT and TT genotypes were 33·92 48·51 and 17·54 %, respectively, and 86·6 % of participants were women. The results showed that subjects with TT genotypes had significantly higher lumbar BMD, T score and z score (P<0·0001). After categorisation by percentage of fat intake (30 % of total energy content as a cut-off point), no interaction was found, but when categorised by fat types, we found an interaction between visfatin genotypes and dietary PUFA intake in terms of the hip T score and z score (P=0·043, B= -0·08; P=0·04, B= -0·078, respectively). There was a significant relationship between high PUFA intake and lower energy and protein intake. When participants were categorised by median PUFA intake (22·8 g), it was concluded that subjects with GG genotype who had high PUFA-intake diets had lower hip z scores and T scores, unlike the other genotypes.

Vitamin D Status and Resting Metabolic Rate May Modify through Expression of Vitamin D Receptor and Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene in Overweight and Obese Adults.

BACKGROUND: Resting metabolic rate (RMR) used to prognosticate and measure the amount of energy required. Vitamin D is known as a new predictor of RMR. The aim of this study is to investigate the relationship between vitamin D effects on RMR in connection with the vitamin D receptor (VDR) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) gene expression. METHODS: We enrolled 298 overweight and obese adults in this cross-sectional study. Body mass index (BMI), fat mass, fat-free mass, insulin level, visceral fat, and vitamin D status were assessed. RMR was measured by means of indirect calorimetry. The real-time polymerase chain reaction using specific primer pairs for VDR and PGC-1α was performed. RESULTS: There were significant differences in terms of fat free mass, fat percentage, insulin levels, RMR/kg body weight, and RMR/BMI, VDR, and PGC-1α among participants were categorized based on the vitamin D status. But after using general linear model for adjusting, all significant results missed their effectiveness except RMR/kg body weight and VDR. Linear regression analysis used to show the mediatory role of VDR and PGC-1α on the RMR/kg body weight and vitamin D status relationship. Our results showed that VDR had a mediatory effect on the relationship between RMR/kg body weight and vitamin D status (ß = 0.38, 95% CI -0.48 to 1.60; ß = -1.24, 95% CI -5.36 to 1.70). However, PGC-1α did not affect the relationship between RMR/kg body weight and vitamin D status (ß = 0.50, 95% CI = -0.02 to 3.42; ß = 0.59, 95% CI 0.14-3.90). CONCLUSION: Our study showed the mediatory effect of VDR gene expression in the association of 25(OH)2D plasma levels and resting metabolic rate among obese individuals.

The associations between dietary patterns and bone health, according to the TGF-ß1 T869→C polymorphism, in postmenopausal Iranian women.

BACKGROUND/OBJECTIVE: Recent studies have shown that dietary variants and genetic variants play a decisive role in the risk of developing osteoporosis. Therefore, the objective of the present study was to examine associations between dietary pattern and bone health, according to the TGF-ß1 T869→C polymorphism, in postmenopausal Iranian women. MATERIALS AND METHODS: In this study, 264 postmenopausal women aged from 46 to 78 years were examined. Body composition was measured by a body composition analyzer and physical activity by the short-form physical activity questionnaire. Bone mineral density was measured by the DEXA method. Dietary patterns were determined using factor analysis on 27 foods groups, employing a valid, reliable 147-item semi-quantitative food frequency questionnaire. The dietary patterns were analyzed by the factor analysis method. Blood samples were taken for measuring blood parameters. DNA samples from participants were genotyped using the RFLP-PCR method. RESULTS: Three dietary patterns were identified, namely: mediterranean diet, traditional diet, and unhealthy diet-one of which was associated with bone health. Postmenopausal women following a Mediterranean diet had lower weight and central obesity (0.05 > P). Higher adherence to a Mediterranean pattern was positively associated with Z-score L2_L4 lumbar spine (0.05 > P). TGF-ß1 T869→C genotypes, after adjustment, were not directly correlated with bone mineral density and body composition (0.05 < P). Moreover, these findings demonstrated that in participants adhering to a Traditional dietary pattern, the C allele carrier group (TC and CC genotypes) had a lower L2_L4 Z-score (P = 0.05). CONCLUSION: It seems that the mediterranean diet can be a beneficial dietary pattern in the prevention of osteoporosis and obesity in postmenopausal women. Furthermore (probably in the C allele carrier group), lower vitamin D intake, coupled with adherence to a traditional dietary pattern, reduces the deposition of TGF-beta and increases the risk of lumbar spine osteoporosis.

Relationship between major dietary patterns and sarcopenia among menopausal women.

BACKGROUND AND AIM: Dietary habits have been associated with the prevalence of the sarcopenia and limited data are available in this field for menopausal women. This study focused on the relationship between dietary patterns and prevalence of the sarcopenia in menopausal women. METHODS: This cross-sectional study was done in 250 menopausal women 45 years old or older. Dietary data were collected using a food-frequency questionnaire and physical activity was assessed by International Physical Activity Questionnaire (IPAQ). Height, weight, skeletal muscle mass, hand grip, and gait speed were measured and sarcopenia was defined based on European Working Group on Sarcopenia in Older People (EWGSOP) guidelines. RESULTS: Using factor analysis, two major dietary patterns were found: a Western pattern (high in commercial beverage, sugar and dessert, snacks, solid fat, potato, high fat dairy, legume, organ meat, fast food, and sweets) and a Mediterranean pattern (high in olive, low-fat dairy, vegetable, fish, nut, and vegetable oil). After adjusting for confounding variables, for the highest vs the lowest tertiles, the Odds Ratio (OR) for sarcopenia was 1.06 [95% confidence interval (CI), 0.47-2.37] in the Western pattern and 0.40 [95% confidence interval (CI), 0.17-0.89] in the Mediterranean pattern. CONCLUSIONS: Our findings suggest that Mediterranean dietary pattern has a favorable role in the prevention of sarcopenia.

Influence of MTHFR gene variations on perceived stress modification: Preliminary results of NURSE study.

Background: High level of perceived stress in nurses is due to a genetic predisposition and environmental stressors. The aim of NURSE (Nursing Unacquainted Related Stress Etiologies) study was to investigate the association of C677T MTHFR gene polymorphism and stress perception among nurses. Methods: In this comprehensive study, 216 female nurses were recruited. Perceived stress was assessed using the Cohen Perceived Stress Scale (PSS). Genomic DNA was extracted from peripheral blood, and MTHFR genotype was detected by the polymerase chain reaction. Results: MTHFR C677T genotype analysis revealed that half of the participants had normal C/C genotype, and the remaining half presented higher frequencies of C/T genotype (39.8%) compared to T/T genotype (10.2%). The mean±SD stress score in morning shift, night shift, and rotation was 15.39±4.75, 15.92±4.94, and 15.83±5.61, respectively (p= 0.7). Perceived stress score was more in highly educated group but it was not significant (p= 0.2). Distribution of different MTHFR genotypes in diverse groups revealed that in groups with more stress score, the frequency of heterozygote (C/T) and homozygote (T/T) genotypes increased. Data revealed that in low stress category, 87% of the participants had a normal genotype. However, in high stress category, 71.3% of the participants had a normal genotype. Conclusion: MTHFR genotype, independent of folate availability and probable confounding parameters, might be a potential risk factor of perceived stress among nurses.

Global DNA methylation as a possible biomarker for diabetic retinopathy.

BACKGROUND: We evaluated whether global levels of DNA methylation status were associated with retinopathy as well as providing a predictive role of DNA methylation in developing retinopathy in a case-control study of 168 patients with type 2 diabetes. METHODS: The 5-methylcytosine content was assessed by reversed-phase high-pressure liquid chromatography of peripheral blood leukocytes to determine an individual's global DNA methylation status in the two groups, either with or without retinopathy. RESULTS: The global DNA methylation levels were significantly higher in diabetic retinopathy patients compared with those in non-retinopathy patients (4.90 ± 0.12 vs. 4.22 ± 0.13, respectively; p = 0.001). There was a significant increasing trend in global DNA methylation levels in terms of progressing retinopathy (without retinopathy, 4.22 ± 0.13; non-proliferative diabetic retinopathy, 4.62 ± 0.17; proliferative diabetic retinopathy, 5.07 ± 0.21) (p = 0.006). Additionally, global DNA methylation independent of retinopathy risk factors, which include dyslipidaemia, hypertension, hyperglycaemia and duration of diabetes, was a predictive factor for retinopathy (OR = 1.53, p = 0.015). CONCLUSIONS: Global DNA methylation is modulated during or possibly before the primary stage of diabetes. This observation verifies the metabolic memory effect of hyperglycaemia in early stage of an aetiological process that leads to type 2 diabetes and its associated complications.

Investigating the effects of 25-hydroxyvitamin D3 on clinical outcomes in multiple sclerosis patients: A randomized, double-blind clinical trial- a pilot study.

BACKGROUND: The primary objective of this clinical trial was to assess whether administrating oral calcifediol (25(OH)D3) could enhance the clinical outcomes of patients diagnosed with multiple sclerosis. METHODS: This clinical trial was designed as a randomized, double-blind, two-arm study, with 25 participants receiving daily 50 µg of calcifediol and 25 people receiving daily 50 µg of cholecalciferol. The primary outcomes were serum levels of 25(OH)D3, number of relapses, changes in Kurtzke Expanded Disability Status Scale (EDSS), the 25-foot walk, and cognitive function. RESULTS: At the end of the trial, delta serum concentrations of 25(OH)D3 were 85.32±40.94 ng/ml in the calcifediol group compared to 13.72±11.56 ng/ml in the cholecalciferol group; 84 % of the calcifediol group and none of the cholecalciferol group had circulating 25(OH)D3 concentrations exceeding 70 ng/ml. While both groups showed an overall trend towards improved cognitive function at the end of the study, the calcifediol group exhibited greater improvements in most cognitive tests. However, the trial had no significant beneficial effects on MS relapse, EDSS score, quality of life, or fatigue in either group, the calcifediol or cholecalciferol. CONCLUSIONS: The trial shows that calcifediol is more effective in rapidly increasing 25(OH)D3 levels in MS patients compared to cholecalciferol when administrated at a similar dosage.

Association between disease-modifying therapies and adverse clinical outcomes in multiple sclerosis patients with COVID-19 infection.

BACKGROUND: This study aimed to consider the main risk factors related to adverse clinical outcomes in MS patients with COVID-19. METHODS: Using the electronic health records systems, this is a cross-sectional study of two years of hospital admissions in terms of COVID-19 in Iran from March 2019 to August 2021. The severities of COVID-19 outcomes were admitted to ICU, hospitalization days, and in-hospital mortality. RESULTS: A total of 1634 hospitalized MS patients with a definite diagnosis of COVID-19 based on PCR were recorded in the electronic health systems. MS patients had a 7% increased risk for longer hospitalization, a 3% increased risk for the need to the ICU, and no increased risk of mortality compared with the general population. MS patients who were taking immunosuppressive (IS)-disease modifying therapies (DMT) had longer hospitalization (adjusted OR=2.06, 95%CI: 1.48, 2.86) and higher mortality risk (adjusted OR=2.05, 95%CI: 1.52, 6.29) compared to patients were under the immunomodulatory (IM)-DMT. There was not any significant association between the types of DMT and ICU (12.2% vs. 12.7%). Besides, MS patients who were vaccinated against COVID-19 before admission had shorter hospitalization (adjusted OR=0.40, 95% CI: 0.18, 0.92). CONCLUSIONS: The current data suggest that MS healthcare providers should consider specific risks of severe COVID-19 infection before starting IS-DMT.