Vitamin D deficiency associations with metabolic, bone turnover and adverse general health markers in community free living adults.

BACKGROUND: Although there is some evidence that vitamin D deficiency is highly prevalent in the Middle East, however its health impact is still not clear. The aim of this study was to assess the prevalence, causes and health implications of vitamin D deficiency in local United Arab Emirates (UAE) citizens. METHODS: A cross-sectional study was conducted on community free living adults living in the city of Al Ain, UAE. Following informed written consent eligible subject's blood and urine samples were taken for measurements of vitamin D [25(OH)D], metabolic and bone turnover markers. Clinical assessment that includes general and self-rated health, muscle health, and physical activity were also performed. RESULTS: A total of 648 subjects (491 female) were included in this analysis. Their mean (SD) age was 38 (12) years. Mean 25(OH)D was 24 ng/ml (range: 4-67) with 286 (44%) subjects found to have vitamin D deficiency (< 20 ng/ml), 234 (36%) subjects have insufficiency (20-32 ng/ml) and 128 (20%) subjects have optimal concentrations (> 32 ng/ml). 25(OH)D concentrations were significantly higher in local indigenous UAE subjects compared to other Arab expatriates (p = 0.071). Although there were no statistically significant differences in clinical markers between groups, however, utra-sensitive C-reactive protein (us-CRP), parathyroid hormone (PTH), body mass index (BMI) and the bone markers U-PYD and PYD/CR were higher in vitamin D deficient older subjects aged ≥50 years and female subjects younger than 50 years respectively compared to those with insufficiency or optimal concentrations (p value < 0.05. Multiple logistic regression analysis revealed significant and independent association between 25(OH)D status and age and sex (p < 0.05). CONCLUSION: Older subjects with vitamin D deficiency have increased BMI, inflammation and PTH compared with those with insufficiency or optimal concentrations. Co-existence of obesity and vitamin D deficiency may have increased adverse health effects.

A randomized, double-blind, placebo-controlled trial of vitamin D supplementation with or without calcium in community-dwelling vitamin D deficient subjects.

BACKGROUND: Although vitamin D deficiency is highly prevalent in the Middle East, very few studies have attempted to measure its health impact. AIMS: We aimed to assess whether vitamin D3 and calcium, either alone or in combination, have health benefit. METHODS: In a 2 × 2 factorial design double-blind, placebo-controlled trial, Community free living adults living in the city of Al Ain, UAE were randomly assigned to receive daily 2000 IU oral vitamin D3 alone, 600 mg calcium alone, oral vitamin D3 (2000 IU per day) combined with 600 mg calcium, or a placebo for 6 months. Primary outcomes were self-rated health and bone turnover markers. RESULTS: Of the 545 randomized, 277 subjects completed 6 months follow up. 25(OH)D levels marginally increased in the two groups received vitamin D3 alone or combined with calcium compared to the decline seen in those who received calcium supplement alone or a placebo. Sub-group analysis revealed that parathyroid hormone (PTH) concentration decreased and Calcium/creatinine ratio increased significantly in the combined vitamin D and Calcium group compared to the vitamin D alone or Calcium alone in contrast to the increase seen in the placebo group [p < 0.05 for between group difference at 6 months]. There were no statistically significant differences between the supplement and placebo groups at the 6 months follow-up in body weight, body mass index (BMI), blood pressure, body pains and general health. CONCLUSION: PTH concentration decreased and calcium/creatinine ratio increased in subjects who received vitamin D and Calcium together compared to those who received vitamin D alone. TRIAL REGISTRATION: NCT02662491 , First registered on 25 January 2016 ( https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S00060CE&selectaction=Edit&uid=U0001M6P&ts=3&cx=scu4cb , Last update: 05 August 2019.

Epimers of Vitamin D: A Review.

In this review, we discuss the sources, formation, metabolism, function, biological activity, and potency of C3-epimers (epimers of vitamin D). We also determine the role of epimerase in vitamin D-binding protein (DBP) and vitamin D receptors (VDR) according to different subcellular localizations. The importance of C3 epimerization and the metabolic pathway of vitamin D at the hydroxyl group have recently been recognized. Here, the hydroxyl group at the C3 position is orientated differently from the alpha to beta orientation in space. However, the details of this epimerization pathway are not yet clearly understood. Even the gene encoding for the enzyme involved in epimerization has not yet been identified. Many published research articles have illustrated the biological activity of C3 epimeric metabolites using an in vitro model, but the studies on in vivo models are substantially inadequate. The metabolic stability of 3-epi-1α,25(OH)2D3 has been demonstrated to be higher than its primary metabolites. 3-epi-1 alpha, 25 dihydroxyvitamin D3 (3-epi-1α,25(OH)2D3) is thought to have fewer calcemic effects than non-epimeric forms of vitamin D. Some researchers have observed a larger proportion of total vitamin D as C3-epimers in infants than in adults. Insufficient levels of vitamin D were found in mothers and their newborns when the epimers were not included in the measurement of vitamin D. Oral supplementation of vitamin D has also been found to potentially cause increased production of epimers in mice but not humans. Moreover, routine vitamin D blood tests for healthy adults will not be significantly affected by epimeric interference using LC-MS/MS assays. Recent genetic models also show that the genetic determinants and the potential factors of C3-epimers differ from those of non-C3-epimers.Most commercial immunoassays techniques can lead to inaccurate vitamin D results due to epimeric interference, especially in infants and pregnant women. It is also known that the LC-MS/MS technique can chromatographically separate epimeric and isobaric interference and detect vitamin D metabolites sensitively and accurately. Unfortunately, many labs around the world do not take into account the interference caused by epimers. In this review, various methods and techniques for the analysis of C3-epimers are also discussed. The authors believe that C3-epimers may have an important role to play in clinical research, and further research is warranted.

Significantly Elevated Levels of Plasma Nicotinamide, Pyridoxal, and Pyridoxamine Phosphate Levels in Obese Emirati Population: A Cross-Sectional Study.

Water-soluble vitamins like B3 (nicotinamide), B6 (pyridoxine), and B9 (folic acid) are of utmost importance in human health and disease, as they are involved in numerous critical metabolic reactions. Not surprisingly, deficiencies of these vitamins have been linked to various disease states. Unfortunately, not much is known about the physiological levels of B6 vitamers and vitamin B3 in an ethnically isolated group (such as an Emirati population), as well as their relationship with obesity. The aim of the present study was to quantify various B6 vitamers, as well as B3, in the plasma of obese and healthy Emirati populations and to examine their correlation with obesity. A sensitive and robust HPLC-MS/MS-based method was developed for the simultaneous quantitation of five physiologically relevant forms of vitamin B6, namely pyridoxal, pyridoxine, pyridoxamine, pyridoxamine phosphate, and pyridoxal phosphate, as well as nicotinamide, in human plasma. This method was used to quantify the concentrations of these vitamers in the plasma of 57 healthy and 57 obese Emirati volunteers. Our analysis showed that the plasma concentrations of nicotinamide, pyridoxal, and pyridoxamine phosphate in the obese Emirati population were significantly higher than those in healthy volunteers (p < 0.0001, p = 0.0006, and p = 0.002, respectively). No significant differences were observed for the plasma concentrations of pyridoxine and pyridoxal phosphate. Furthermore, the concentrations of some of these vitamers in healthy Emirati volunteers were significantly different than those published in the literature for Western populations, such as American and European volunteers. This initial study underscores the need to quantify micronutrients in distinct ethnic groups, as well as people suffering from chronic metabolic disorders.

Role of Functional Biomarkers to Identify Early Vitamin B12 Deficiency in Patients with Sleeve Gastrectomy: A Cross-Sectional Study.

Background and objectives: Although laparoscopic sleeve gastrectomy (LSG) is effective for obesity management, postoperative vitamin B12 (B12) deficiency is of major concern. In this cross-sectional study, we assessed the levels of B12 and its related functional biomarkers, namely, total homocysteine (tHcy), methylmalonic acid (MMA), folate, methylcitric acid (MCA), and hemoglobin (Hb), in one-year postoperative LSG patients and matched controls. Materials and Methods: Plasma B12, tHcy, MMA, folate, and MCA were measured in matched controls (n = 66) and patients (n = 71) using validated liquid chromatography-tandem mass spectrometry techniques and protocols in the United Arab Emirates (UAE). Results: The median B12 concentration in patients (177 pmol/L) was significantly lower (p < 0.001) than in the controls (334.7 pmol/L). The tHcy and MMA levels were significantly increased (p < 0.001 and p = 0.011, respectively) and folate levels were significantly decreased (p = 0.001) in the LSG patients compared to the controls. Interestingly, no significant difference in MCA levels were observed between the two groups. The levels of tHcy and MMA were concomitantly increased with the decreased folate levels in postoperative LSG patients when compared with the controls. The Hb levels were significantly lower in males and females in the patient group compared with those in the control group, respectively (p = 0.005 and p = 0.043). Conclusions: This is the first report of serum levels of B12 and its functional biomarkers in postoperative LSG patients among a local population from the UAE. Our findings revealed significant alterations of the B12 biomarkers, total B12, MMA, and tHcy in one-year postoperative LSG patients.

Total adiponectin in overweight and obese subjects and its response to visceral fat loss.

BACKGROUND: Visceral obesity and related diabetes is reaching epidemic proportions in the United Arab Emirates (UAE). Adiponectin is a hormone that is secreted by adipose tissue and may play an important role in obesity-related morbidity. The aim of this study was to investigate total adiponectin levels in overweight and obese UAE subjects visiting health care facilities for weight management. METHODS: All overweight and obese subjects visiting community health centers were invited to take part in the study. Two hundred and six participants received individualized structured dietary education for weight management. Demographic data, anthropometric measurements and fasting venous blood samples were taken for measurements of total adiponectin and markers of inflammation and nutritional status at baseline and follow up. Multivariate analysis was performed to determine the independent effects of prognostic factors on serum adiponectin levels. RESULTS: A total of 193 (93%) females with a mean age (±SD) 36 ± 11 years were included in the analysis. During a follow up period of 427 ± 223 days, participants received 13 ± 5 structured dietary education sessions. We observed decreased levels of total adiponectin with increasing quartiles of both waist circumference (WC) and body mass index (BMI). Male gender and history of both gestational and type 2 diabetes were associated with significantly lower total adiponectin levels (p < 0.05). After adjusting for age, gender, BMI and hip circumference, multiple regression analysis revealed a significant and independent association between waist circumference and total adiponectin levels. At follow up visceral fat loss was associated with a significant decrease in inflammatory markers and a non-significant increase in total adiponectin levels. CONCLUSION: Increased visceral fat in overweight and obese subjects is associated with decreased total adiponectin levels. The health benefits of increasing adiponectin levels using different dietary intervention strategies need to be explored in larger studies. TRIAL REGISTRATION: NCT01691365 , registered on 11/09/2012.

Association between muscle function, cognitive state, depression symptoms and quality of life of older people: evidence from clinical practice.

BACKGROUND: Although low muscle function/strength is an important predictor of poor clinical outcome in older patients, information on its impact on mental health in clinical practice is still lacking. AIMS: The aim of this report is to measure the impact of low muscle function measured by handgrip strength on mental health of older people during both acute illness and recovery. METHODS: Four hundred and thirty-two randomly selected hospitalized older patients had their baseline demographic and clinical characteristics assessed within 72 h of admission, at 6 weeks and at 6 months. Low muscle strength-handgrip was defined using the European Working Group criteria. Mental health outcome measures including cognitive state, depression symptoms and quality of life were also measured. RESULTS: Among the 432 patients recruited, 308 (79%) had low muscle strength at baseline. Corresponding figures at 6 weeks and at 6 months were 140 (73%) and 158 (75%). Patients with poor muscle strength were significantly older with increased disability and poor nutritional status compared with those with normal muscle strength. After adjustment for age, gender, disability, comorbidity including severity of acute illness and body mass index patients with low muscle strength had worse cognitive function, quality of life and higher depression symptoms compared with those with normal muscle strength over a 6-month period (p < 0.05). CONCLUSION: Poor muscle strength in older people is associated with poor cognitive state and quality of life and increased depression symptoms during both acute illness and recovery.

Impact of poor muscle strength on clinical and service outcomes of older people during both acute illness and after recovery.

BACKGROUND: Although Low muscle strength is an important predictor of functional decline in older people, however information on its impact on clinical and service outcomes in acute care settings is still lacking. The aim of this study is to measure the impact of low muscle strength on clinical and service outcomes in older adults during both acute illness and recovery. METHODS: Randomly selected 432 hospitalised older patients had their clinical characteristics and nutritional status assessed within 72 h of admission, at 6 weeks and at 6 months. Low muscle strength-hand grip was defined using the European Working Group criteria. Health outcome measures including nutritional status, length of hospital stay, disability, discharge destination, readmission and mortality were also measured. RESULTS: Among the 432 patients recruited, 308 (79%) had low muscle strength at baseline. Corresponding figures at 6 weeks and at 6 months were 140 (73%) and 158 (75%). Patients with poor muscle strength were significantly older, increasingly disabled, malnourished and stayed longer in hospital compared with those with normal muscle strength. A significantly higher number of patients with normal muscle strength discharged home independently compared with those with poor muscle strength (p < 0.05). One-year death rate was lower in patients with normal muscle strength 5(6%), compared with those with poor muscle strength 52(15%), however, results were not statistically significant after adjusting for other poor prognostic indicators [adjusted hazard ratio 0.74 (95% CI: 0.14-3.87), p = 0.722]. CONCLUSION: Poor muscle strength in older people is associated with poor clinical service outcomes during both acute illness and recovery.

Zinc Depletion Increases Readmission in Older Patients: An Example of Interactions Between Nutrition and Disease.

Background: ill health may lead to poor nutrition and poor nutrition to ill health, so identifying priorities for management still remains a challenge. The aim of this report is to present data on the impact of plasma zinc (Zn) depletion on important health outcomes after adjusting for other poor prognostic indicators in hospitalised patients. METHODS: Hospitalised acutely ill older patients who were part of a large randomised controlled trial had their nutritional status assessed using anthropometric, hematological and biochemical data. Plasma Zn concentrations were measured at baseline, 6 weeks and at 6 months using inductively- coupled plasma spectroscopy method. Other clinical outcome measures of health were also measured. RESULTS: A total of 345 patients assessed at baseline, 133 at 6 weeks and 163 at 6 months. At baseline 254 (74%) patients had a plasma Zn concentration below 10.71 µmol/L indicating biochemical depletion. The figures at 6 weeks and 6 months were 86 (65%) and 114 (70%) patients respectively. After adjusting for age, co-morbidity, nutritional status and tissue inflammation measured using CRP, only muscle mass and serum albumin showed significant and independent effects on plasma Zn concentrations. The risk of non-elective readmission in the 6-months follow up period was significantly lower in patients with normal Zn concentrations compared with those diagnosed with Zn depletion (adjusted hazard ratio 0.62 (95% CI: 0.38 to 0.99), p = 0.047. CONCLUSIONS: Zn depletion is common and associated with increased risk of readmission in acutely-ill older patients, however, the influence of underlying comorbidity on these results can not excluded.

Poor vitamin C status is associated with increased depression symptoms following acute illness in older people.

BACKGROUND: Vitamin C has important physical and mental health benefits and plasma concentrations reflect recent intakes. Inflammation associated with any acute illness can lead to poor appetite and low food intake in older people. The aims of this report were to assess the prevalence and clinical significance of vitamin C deficiency among hospitalized acutely-ill older patients. METHODS: Three hundred and twenty two patients (152 [47%] female), aged 65 yrs. and over who took part in a randomized, double blind, placebo-controlled trial had their nutritional status assessed from anthropometric, hematological and biochemical data at baseline, and after 6 weeks and 6 months. Vitamin C was measured using a fluorimetric technique and logistic regression analysis was performed to determine the influence of a number of clinical indicators, including tissue inflammation measured using C-reactive protein on vitamin C concentrations. Clinical outcome measures including symptoms of depression were also compared between patients with vitamin C deficiency and those with normal levels. RESULTS: At baseline, 116 (36%) patients had a vitamin C concentration below 11 µmol/L indicating biochemical depletion. The figures at 6 weeks and 6 months were 28 (22%) and 44 (28%) patients, respectively. Older age, male gender, smoking, increased dependency and tissue inflammation were associated with lower vitamin C concentrations. Patients with vitamin C biochemical depletion had significantly increased symptoms of depression compared with those with higher concentrations at baseline (p=0.035) and at 6 weeks (p=0.028). CONCLUSIONS: A high proportion of older patients had sub-optimal vitamin C status and this was associated with increased symptoms of depression.

Unraveling the complex interplay between obesity and vitamin D metabolism.

Vitamin D deficiency and obesity are a worldwide health issue. Obesity refers to the accumulation of excessive fats in the body which could lead to the development of diseases. Obese people have low vitamin D levels for several reasons including larger volume of distribution, vitamin D tightly bound in fatty tissues, reduced absorption, and diets with low vitamin D. Accurately measuring vitamin D metabolites is challenging. The Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed and validated for the analysis of vitamin D metabolites in the serum. Blood samples were collected from 452 subjects which consisted of baseline (vitamin D deficient obese subjects), follow-up (supplemented obese subjects), and healthy volunteers. The vitamin D metabolites were separated adequately by the developed UHPLC-MS/MS method. Moreover, the validation criteria for the method were within an acceptable range. The baseline, follow-up and even healthy volunteers were deficient in 25OHD3 and 25OHD2. The baseline and healthy subjects had comparable concentration of vitamin D2 and D3. However, healthy subjects had a higher concentration of 25OHD and its epimer compared to the baseline subjects. The vitamin D3 was increased significantly in the follow- up subjects; therefore, the 25OHD3 was increased significantly compared to the baseline as well; however, the increase was insufficient to achieve the optimal range. The UHPLC-MS/MS method test was applied successfully on estimation of vitamin D metabolites in subjects. This study indicates the significance of taking into account the metabolic and storage effects when evaluating the vitamin D status in obese subjects.

Frequency of Vitamin D Receptor Gene Polymorphisms in a Population with a very High Prevalence of Vitamin D Deficiency, Obesity, Diabetes and Hypertension.

BACKGROUND: Although vitamin D levels and underlying vitamin D receptor (VDR) genetic polymorphisms have been linked to many common diseases including obesity, the association remains unclear. There is also co-existence of pathologically high proportions of obesity and vitamin D deficiency conditions in our UAE society. We therefore aimed to determine the genotypes and allele percentage frequency distribution of four polymorphisms-FokI, BsmI, ApaI and TaqI-in the VDR gene in healthy Emirati individuals and their association with vitamin D levels and chronic conditions including diabetes mellitus, hypertension and obesity. METHODS: 277 participants who were part of a randomized controlled trial had their assessment that included clinical and anthropometric data. Whole blood samples were taken for measurements of vitamin D [25(OH) D], four vitamin D receptor gene polymorphism SNPs, including BsmI, FokI, TaqI and ApaI, metabolic and inflammatory markers and related biochemical variables. Multiple logistic regression analysis was used to assess the influence of vitamin D receptor gene SNPs on vitamin D status after adjusting for clinical parameters known to influence vitamin D status in the study population. RESULTS: Overall, 277 participants with a mean (±SD) age of 41 ± 12, 204 (74%) of them being female, were included in the study. There were statistically significant differences in vitamin D concentrations between different genotypes of the four VDR gene polymorphisms (p < 0.05). There were, however, no statistically significant differences in vitamin D concentrations between subjects with and those without the four VDR gene polymorphisms genotype and alleles except for AA and AG and allele G in Apal SNP (p < 0.05). Multivariate analysis revealed no significant independent associations between vitamin D status and the four VDR gene polymorphisms after adjusting for dietary intake, physical activity, sun exposure, smoking and body mass index. In addition, no significant differences were found in the frequency of the genotypes and alleles of the four VDR genes among patients with obesity, diabetes and hypertension compared to those without these medical conditions. CONCLUSIONS: Although we found statistically significant differences in vitamin concentrations between different genotypes of the four VDR gene polymorphisms, multivariate analysis revealed no association after adjusting for clinical parameters known to influence vitamin D status. Furthermore, no association was found between obesity and related pathologies and the four VDR gene polymorphisms.

Increased Fruit and Vegetable Consumption Mitigates Oxidative Damage and Associated Inflammatory Response in Obese Subjects Independent of Body Weight Change.

INTRODUCTION: The growing prevalence of obesity and related type 2 diabetes is reaching epidemic proportions in the Gulf countries. Oxidative damage and inflammation are possible mechanisms linking obesity to diabetes and other related complications, including cardiovascular disease (CVD). AIMS: To measure the effects of increased fruit and vegetable consumption on body weight, waist circumference, oxidative damage, and inflammatory markers. MATERIALS AND METHODS: We recruited and followed up with 965 community free-living subjects. All recruited subjects had fruit and vegetable intakes, physical activity, antioxidants, and markers of oxidative damage and inflammation measured at baseline and follow up. A validated, semi-quantitative food-frequency questionnaire was used to assess subjects' fruit and vegetable consumption. We stratified subjects based on their daily fruit and vegetable consumption and compared metabolic risk factors between those with high fruit and vegetable consumption and those with low consumption. A multiple logistic regression analysis was performed to determine the independent effects of fruit and vegetable intake on changes in body weight and waist circumference (WC). RESULTS: A total of 965 community free-living subjects (801 (83%) females, mean (SD) age 39 ± 12 years) were recruited and followed up with for a mean (SD) period of 427 ± 223 days. Using WHO cut-off points for body mass index (BMI), 284 (30%) subjects were overweight and 584 (62%) obese, compared to 69 (8%) at normal body weight. An increased fruit and vegetable consumption was associated with a significant decrease in inflammatory markers (hs CRP, TNF-α) and oxidative damage markers (TBARs) and with increased antioxidant enzymes (catalase, glutathione peroxidase) compared to a low consumption (p < 0.05). The benefits of an increased fruit and vegetable consumption in obese subjects was independent of changes in body weight and WC and was maintained at follow up. CONCLUSION: Our results support the beneficial role of a higher fruit and vegetable intake in obese subjects independent of changes in body weight and WC.

Mechanisms and Effect of Increased Physical Activity on General and Abdominal Obesity and Associated Metabolic Risk Factors in a Community with Very High Rates of General and Abdominal Obesity.

BACKGROUND: The growing prevalence of obesity and related type 2 diabetes is reaching epidemic proportions in the UAE. Physical inactivity is one of the possible factors linking obesity to diabetes and other related complications. However, the molecular mechanisms through which physical inactivity is contributing to increased obesity-related pathologies are not clear. AIMS: to measure the effects of increased physical activity on obesity and related metabolic risk factors. MATERIALS AND METHODS: We investigated the effects of physical activity on body weight, waist circumference (WC) and metabolic risk factors in 965 community free-living Emirati subjects. Physical activity, dietary intake, antioxidant enzymes and markers of oxidative damage and inflammation were measured both at baseline and follow up. A validated questionnaire was used to assess occupation and leisure-related physical activity. We compared metabolic risk factors between subjects stratified by physical activity levels. The Cox proportional hazards analysis was used to determine the independent effects of increased physical activity on presence and absence of obesity, body weight and waist circumference (WC) change at follow up. RESULTS: A total of 965 community free-living subjects [801 (83%) females, mean (SD) age 39 ± 12 years] were recruited and followed up with for a period of 427 ± 223 days. Using WHO cut-of-points for body mass index (BMI), 284 (30%) subjects were overweight and 584 (62%) subjects were obese, compared to 69 (8%) at normal body weight. We found men to be more physically active than women at both leisure and work times. BMI, hip circumference, total body fat, HDL and inflammatory markers (us CRP, TNF) were significantly higher in female subjects, whilst fat free-mass, WC, blood pressure and HbA1c were higher in male subjects (p < 0.05). Hypertension and diabetes were more common in male subjects compared to female subjects (p < 0.05). Increased physical activity both at baseline and follow up were associated with decreased BMI, WC and inflammatory markers, including us-CRP and TNF. Increased physical activity was associated with significant decrease in abdominal obesity in female subjects and general obesity in both male and females after adjusting for important prognostic indicators [hazard ratio (95% CI): 0.531 (0.399, 0.707); p < 0.001; 0.475 (0.341, 0.662); p < 0.001 respectively]. CONCLUSION: Our findings suggest that increased physical activity may decrease the risk of obesity and also mitigate the associated oxidative damage and inflammatory responses.

Effects of mixed dietary supplements on total plasma homocysteine concentrations (tHcy): a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although a number of studies have reported raised total plasma homocysteine (tHcy) concentrations in free-living older people, there are no data on homocysteine response to a mixed nutrient supplement in older patients. A raised plasma homocysteine concentration in older patients is partly a reflection of their co-morbidity, including impaired renal function, and there is uncertainty about the extent to which dietary interventions can improve plasma tHcy. AIM: To determine the plasma tHcy response to dietary supplements during acute illness. METHODS: Two-hundred and thirty-six hospitalized, acutely ill older patients, who were part of a randomized double-blind placebo-controlled trial, were assigned to receive a daily oral nutritional supplement drink containing 1.3 mg of vitamin B2, 1.4 mg of vitamin B6, 1.5 µg of B12, 200 µg of folic acid, or a placebo, for 6 weeks. Outcome measures were plasma tHcy concentration at baseline, 6 weeks, and 6 months. RESULTS: The mean plasma tHcy concentration fell among patients given the supplements (mean difference 4.1 µmol/L [95 % C.I, 0.14 to 8.03), p = 0.043], but tHcy concentration increased between 6 weeks and 6 months, after patients stopped taking the supplements [mean difference -2.0 µmol/L (95 % C.I, -03.9 to -0.18), p = 0.033]. About 46 % of patients in the placebo group and 55 % of patients in the supplement group had hyperhomocysteinemia (>14 µmol/L) at baseline compared with 45 % and 29 % at the end of the treatment period. CONCLUSIONS: A mixed nutrient supplement containing physiological amounts of B vitamins significantly reduced plasma tHcy concentrations in older patients recovering from acute illness.

Vitamin D [25(OH)D] metabolites and epimers in obese subject: Interaction and correlations with adverse metabolic health risk factors.

BACKGROUND: Although both vitamin D deficiency and obesity are highly prevalent in the UAE, the role of vitamin D metabolites in mediating obesity-related adverse health effects is not clear. We aimed to assess the role of vitamin D metabolites as potential mediators in the association between obesity, inflammation and metabolic risk factors. METHODS: 277 participants who were part of a randomized controlled trial had their assessment that included clinical, anthropometric and physical activity data at baseline and at 6 months. Blood and urine samples were taken for measurements of serum 25(OH)D, 25(OH)D metabolites including 25(OH)D3), 25(OH)D2), 1,25(OH)2D3, 3-Epi-D3), metabolic and inflammatory markers and related biochemical variables. Multiple regression analysis used to assess the role of 25(OH)D metabolites in mediating the effect of increasing body mass index (BMI) on inflammation and metabolic risk factors. RESULTS: Overall, 277 participants with complete 6 months follow up with a mean (±SD) age of 41 ± 12 and 204 (74%) female were included in the study. Blood pressure, inflammatory, metabolic and lipid profile markers significantly increased in overweight and obese subjects compared to subjects with normal BMI both at baseline and at 6 months (p < 0.05). 25(OH)D revealed significant association with age, gender, HbA1c and type 2 diabetes (p < 0.05). No statistically significant changes in any of 25(OH)D metabolites assessed. Multivariate analysis revealed significant and independent associations between BMI and important inflammatory and metabolic risk factors (p < 0.05). No similar association observed with 25(OH)D metabolites. CONCLUSION: Although we found significant association between 25(OH)D and prevalence of type 2 diabetes, we found no evidence however to support a role of 25(OH)D metabolites in mediating the effect of BMI on inflammatory or metabolic risk factors.

Urinary Oxidative Damage Markers and Their Association with Obesity-Related Metabolic Risk Factors.

Oxidative damage and inflammation are possible mechanisms linking obesity to diabetes and related complications. This study investigates the levels of oxidative damage markers in the urine of community free-living subjects with increased prevalence of obesity. METHODS: Participants were assessed regarding clinical, anthropometric, and physical activity data at baseline and at 6 months. Blood and urine samples were taken for the measurements of oxidative markers in urine ((glutathione (GSH), thiobarbituric acid reactive substances (TBARS), pteridine, 8-isoprostane and 8-hydroxy-2'-deoxyguanosine (8-OH-dG)), metabolic and inflammatory markers, and related biochemical variables in the blood. Univariate and multiple regression analyses were used to assess the association between oxidative markers and other clinical prognostic indicators. RESULTS: Overall, 168 participants with a complete 6-month follow-up with a mean (±SD) age of 41 ± 12 (119 (71%) females) were included in the study. In multiple regression analysis, log-transformed urinary pteridine levels were significantly correlated with log-transformed urinary GSH, 8-isoprostane, and TBARS after adjusting for urinary creatinine at both baseline and follow-up. Significant correlations were also found between oxidative damage markers and cardiovascular disease risk factors, including systolic blood pressure, HbA1c, plasma glucose, us-C-reactive proteins, total cholesterol, and HDL. Higher TBARS levels were found in males and diabetic subjects, with lower GSH in diabetic hypertensive and obese subjects, but the latter result did not reach statistical significance. We found nonsignificantly higher TBARS, 8-isoprostane, and pteridine levels in smokers compared to those in nonsmokers. All measured urinary oxidative damage markers levels were higher in obese subjects compared with normal-weight subjects, but results did not reach statistical significance. CONCLUSION: we found significant associations between urinary oxidative damage and metabolic risk factors, and higher levels of urinary oxidative damage markers in diabetic, hypertensive, smoker, and male subjects.

Score Gains on the NBME Subject Examinations in Internal Medicine Among Clerkship Students: a Two-Year Longitudinal Study from the United Arab Emirates.

Background: The impact of clinical proficiency on individual student scores on the National Board of Medical Examiners (NBME) Subject Examinations remains uncertain. We hypothesised that increasing the length of time spent in a clinical environment would augment students' performance. Methods: Performance on the NBME Subject Examination in Internal Medicine (NBME-IM) of three student cohorts was observed longitudinally. Scores at the end of two unique internal medicine clerkships held at the third and fourth years were compared. The score differences between the two administrations were compared using paired t-tests, and the effect size was measured using Cohen's d. Moreover, linear regression was used to assess the correlation between the NBME-IM score gains and performance on a pre-clinical Comprehensive Basic Science Examination (CBSE). A two-tailed p-value <0.05 was considered significant. Results: Of the 236 students enrolled during the third year, age, gender, CBSE, and NBME-IM scores were similar across all cohorts. The normalised score gain on the NBME-IM at the fourth year was 9.5% (range -38 to +45%) with a Cohen's d of 0.47. However, a larger effect size with a Cohen's d value of 0.96 was observed among poorly scoring students. Performance on the CBSE was a significant predictor of score gain on the NBME-IM (R 0.51, R 2 0.26, p-value < 0.001). Conclusions: Despite the increased length of clinical exposure, modest improvement in students' performance on repeated NBME-IM examination was observed. Medical educators need to reconsider how the NBME-IM is used in clerkship assessments.

Testing homocysteine-induced neurotransmitter deficiency, and depression of mood hypothesis in clinical practice.

BACKGROUND: high total plasma homocysteine (tHcy) levels may cause neurotransmitter deficiency, and consequently depression of mood. We have recently shown that mixed oral nutritional supplements containing B-group vitamins led to a statistically significant benefit on depressive symptoms. The aim of this report was to examine the association between elevated plasma tHcy and symptoms of depression in older patients. METHODS: two-hundred and thirty-six hospitalised acutely ill older patients, who were part of a randomised double-blind placebo-controlled trial, were assigned to receive daily mixed oral nutritional supplements containing B-group vitamins or a placebo for 6 weeks. Outcome measures included symptoms of depression measured using Geriatric Depression score and plasma tHcy levels. RESULTS: the mean tHcy concentration fell by 22% among patients given the supplements compared with the placebo group (mean difference 4.1 µmol/l (95% CI: 0.14-8.03), P = 0.043). tHcy concentrations was divided into four quartiles and analysed against depression scores. tHcy concentrations in the first relative to the fourth quartile of the distribution were associated with a lower depression symptoms at the end of the supplement period (Geriatric depression score r = -0.20, P = 0.042). CONCLUSIONS: lower plasma tHcy concentrations were associated with reduced depression symptoms in older patients recovering from acute illness.

Glycemic indices of five varieties of dates in healthy and diabetic subjects.

BACKGROUND: This study was designed to determine the glycemic indices of five commonly used varieties of dates in healthy subjects and their effects on postprandial glucose excursions in individuals with type 2 diabetes mellitus. METHODS: Composition analysis was carried out for five types of dates (Tamer stage). The weights of the flesh of the dates equivalent to 50 g of available carbohydrates were calculated. The study subjects were thirteen healthy volunteers with a mean (± SD) age of 40.2 ± 6.7 years and ten participants with type 2 diabetes mellitus (controlled on lifestyle measures and/or metformin) with a mean HbA1c (± SD) of 6.6 ± (0.7%) and a mean age (± SD) of 40.8 ± 5.7 years. Each subject was tested on eight separate days with 50 g of glucose (on 3 occasions) and 50 g equivalent of available carbohydrates from the 5 varieties of date (each on one occasion). Capillary glucose was measured in the healthy subjects at 0, 15, 30, 45, 60, 90 and 120 min and for the diabetics at 0, 30, 60, 90, 120, 150 and 180 min. The glycemic indices were determined as ratios of the incremental areas under the response curves for the dates compared to glucose. Statistical analyses were performed using the Mann-Whitney U test and repeated measures analysis of variance. RESULTS: Mean glycemic indices ± SEM of the dates for the healthy individuals were 54.0 ± 6.1, 53.5 ± 8.6, 46.3 ± 7.1, 49.1 ± 3.6 and 55.1 ± 7.7 for Fara'd, Lulu, Bo ma'an, Dabbas and Khalas, respectively. Corresponding values for those with type 2 diabetes were very similar (46.1 ± 6.2, 43.8 ± 7.7, 51.8 ± 6.9, 50.2 ± 3.9 and 53.0 ± 6.0). There were no statistically significant differences in the GIs between the control and the diabetic groups for the five types of dates, nor were there statistically significant differences among the dates' GIs (df = 4, F = 0.365, p = 0.83). CONCLUSION: The results show low glycemic indices for the five types of dates included in the study and that their consumption by diabetic individuals does not result in significant postprandial glucose excursions. These findings point to the potential benefits of dates for diabetic subjects when used in a healthy balanced diet. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01307904.