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Vitamin D is endowed with a number of biological properties, including down-regulation of inflammation, and might contribute to the pathogenesis of autism spectrum disorders (ASD). Vitamin D binds to the vitamin D Receptor (VDR); the biological activity of the ensuing complex depends on VDR FokI, BsmI, ApaI, and TaqI gene polymorphisms. We evaluated such Single Nucletoide Polymorphismsm (SNPs) in a cohort of 100 Italian families with ASD children. FokI genotype distribution was skewed in ASD children compared with their healthy sibs (Pc = 0.03 2 df) and to a group of 170 Italian healthy women (HC) (Pc = 0.04 2 df). FokI genotype and allelic distribution skewing were also observed in mothers of ASD children compared to HC (Pc = 0.04 2 df). Both Transmission Disequilibrium Test for single loci and haplotype analysis distribution revealed a major FokI (C) allele-mediated protective effect, which was more frequently transmitted (73%) than not transmitted to healthy sibs (P = 0.02). A protective FokI-, BsmI-, ApaI-, and TaqI (CCAG) haplotype was more frequently carried by healthy sibs than by ASD children (P = 1 × 10-4 ; OR: 0.1, 95% CI: 0.03-0.4) too. Finally, a strong gene-dose association of FokI (T) allele with both higher Childhood Autism Rating Scale score (Pc = 0.01) and, particularly, with hyperactivity behavior (Pc = 0.006) emerged in ASD children. Because the protein produced by the FokI (T) allele is transcriptionally less active than that produced by the FokI (C) allele, the reduced biological activity of the vitamin D/VDR complex prevalent in ASD could favor ASD- and maternal immune activation- associated inflammation. Vitamin D supplementation might be useful in preventative and rehabilitation protocols for ASD. Autism Res 2020, 13: 680-690. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Vitamin D deficiency and Vitamin D receptor (VDR) polymorphisms are associated with structural and functional brain abnormalities and behavioral disorders. We analyzed the association of VDR gene polymorphisms in a cohort of 100 Italian families with ASD children. A strong correlation between one of the VDR polymorphisms and hyperactivity behavior was evidenced in ASD children. In healthy mothers, the same VDR polymorphism was also correlated with an increased risk of giving birth to children with ASD.

BACKGROUND: All proposed definitions of sarcopenia include the measurement of muscle mass, but the techniques and threshold values used vary. Indeed, the literature does not establish consensus on the best technique for measuring lean body mass. Thus, the objective measurement of sarcopenia is hampered by limitations intrinsic to assessment tools. The aim of this study was to review the methods to assess muscle mass and to reach consensus on the development of a reference standard. METHODS: Literature reviews were performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis working group on frailty and sarcopenia. Face-to-face meetings were organized for the whole group to make amendments and discuss further recommendations. RESULTS: A wide range of techniques can be used to assess muscle mass. Cost, availability, and ease of use can determine whether the techniques are better suited to clinical practice or are more useful for research. No one technique subserves all requirements but dual energy X-ray absorptiometry could be considered as a reference standard (but not a gold standard) for measuring muscle lean body mass. CONCLUSIONS: Based on the feasibility, accuracy, safety, and low cost, dual energy X-ray absorptiometry can be considered as the reference standard for measuring muscle mass.

This review emphasizes the safety profile of intra-articular hyaluronic acid treatment of knee osteoarthritis, as well as its moderate but real efficacy on symptoms, which is in the same range than other pharmacological modalities used in this indication. Effectiveness of intra-articular hyaluronic acid has also been highlighted based on ‘real-life' data, together with the clinical benefit of systematic repeated treatment cycles, and the influence of the molecular weight of hyaluronic acid on treatment outcome. These aspects should be particularly helpful to clinicians when making personalized care decisions.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with insulin resistance, even in the absence of overweight/obesity. The aim of the present study is to examine the global serum proteomic profile of adolescent, normal-weight females with PCOS in order to gain novel insight in the association of this endocrine disorder with insulin physiology and to identify novel circulating markers that can guide intervention protocols. Methods: Non-depleted serum from normal-weight (BMI: 18–23 kg m −2 ), adolescent females (13–21 years old) with PCOS (n = 20) is compared to BMI- and age-matched healthy controls (n = 20) using our 3D quantitative proteomics methodology. Serum samples from study participants are randomly pooled to form four biological replicates of females with PCOS and four of healthy controls (n = 5 per sample pool). Results: One-hundred and twenty-six proteins are differentially expressed in females with PCOS compared to controls. Gene ontology analysis shows significant enrichment for terms related to inflammatory immune response, metabolism and insulin-like growth factor receptor signaling pathway. Circulating levels of IGF-1 and -2 and IGFBP-2, -3, and -4 are found to be lower in females with PCOS compared to healthy controls. Conclusions: The present serum proteomics study provides insight into the pro-inflammatory status and insulin dysregulation in young females with PCOS and identifies potential serological markers that can guide early intervention protocols.

Background We aimed to compare the prevalence of childhood obesity and other cardiometabolic risk factors from two independent cohorts (2008 and 2013) in Riyadh, Saudi Arabia. Methods A total of 4549 adolescents aged 12–18 years [2454 boys, 2095 girls], taken from two independent cohorts, 5 years apart (2008 and 2013), were included. Anthropometrics were measured, and fasting blood samples were taken to ascertain glucose and lipid profile. Results The overall prevalence of obesity was significantly higher in 2013 [15.3 (95% confidence interval 13.7–16.9)] than 2008 [12.6 (11.3–13.9)] (P = 0.012). Stratified by sex, the prevalence of obesity among boys was significantly higher in 2013 than 2008 [2008 = 12.0 (10.3–13.7) versus 2013 = 17.4 (15.1–19.7); P

Background: Obesity is a risk factor for both vitamin D deficiency and cardiovascular disease. A link between vitamin D status optimisation and improved cardiometabolic profile among adults with obesity could inform public health initiatives. Methods: PubMed, Embase and Web of Science were searched for interventional studies examining the effects of vitamin D status improvement on cardiovascular risk factors (anthropometric measures, lipid profile, blood pressure, glucose tolerance) among nondiabetic adults with obesity. Results: Seventeen publications reporting results from 11 different studies were included. Number of participants ranged from 34 to 1179 subjects. Duration was between 6 weeks and 4 years. Vitamin D was administered as a supplement in ten studies (1000 IU daily to 120 000 IU fortnightly). In one study, participants were advised to increase sunlight exposure and dietary vitamin D intake. The random and fixed-effects meta-analysis showed that vitamin D significantly increased systolic blood pressure and LDL-C levels. The fixed-effects model also indicated a significant decrease in triglyceride levels, which was not evident using the random-effects model. Caution should be given to these results given the small number of studies used and the high heterogeneity between studies for the two latter outcomes. Additionally, a subset of eligible studies with compatible data presentation was included in the meta-analysis. Conclusion: This systematic review highlights a paucity of interventional studies examining the effects of vitamin D status improvement on cardiovascular risk factors among otherwise healthy adults with obesity. Large-scale studies at pharmacologically relevant doses and with sufficient duration are warranted.

Background Irisin, a novel myokine, has been shown to increase following vigorous exercise, with studies suggesting that it mediates some of the beneficial effects of exercise. Irisin might play a role in ‘browning’ of white adipocytes, thus increasing energy expenditure. The role of irisin in exercise and energy expenditure in subjects with diabetes mellitus type 2 (DMT2) remains largely unknown. We aimed to investigate the association between circulating irisin and habitual physical activity in subjects with and without DMT2. Material and methods In this cross-sectional study, 164 Saudi adults: 81 non-DMT2 controls [age: (mean ± SD) 51·6 ± 10·9; BMI: 29·6 ± 4·3 kg/m2] and 83 DMT2 subjects [age: 54·3 ± 10·3 year; BMI: 29·4 ± 4·7 kg/m2] were studied. Anthropometric and fasting serum biochemical data were collected. Circulating irisin was measured using an enzyme-linked immunosorbent assay (ELISA). Frequency intensity time (FIT) index was used to assess the level of habitual physical activity. Results We observed significantly higher levels of irisin in DMT2 subjects than in controls (P < 0·001). FIT index was positively associated (r = 0·20, P = 0·03) with circulating irisin in controls only. Additionally, irisin levels were significantly higher in tertile 3 (0·75 ± 0·07 μg/mL) than tertile 1 (0·49 ± 0·06 μg/mL) of the FIT index in healthy controls, whilst no such relation with physical activity was observed in DMT2 subjects. Conclusion This cross-sectional study has shown a weak association of irisin with physical activity levels in healthy controls but not in DMT2 subjects, suggesting the possibility of discordant regulation in the condition of DMT2.

Background: The aim of this study is to assess the short-term effects of non-surgical periodontal therapy (NSPT) on the gingival crevicular fluid (GCF) cytokine profile in sites with standardized periodontal bony defects in beagle dogs with and without diabetes. Methods: Four beagle dogs with streptozotocin (STZ)-induced diabetes and four healthy dogs were included. Fasting blood glucose levels were measured using a glucometer. In all animals, a 3-walled bony defect was created on the mesial surface of the second premolar and first molar in all quadrants. After 12 weeks, all animals underwent weekly NSPT for 3 weeks. Baseline and post-NSPT GCF samples were collected, and levels of interleukin (IL)-1, IL-1b, IL-6, IL-8, and tumor necrosis factor (TNF)-a were measured using enzyme-linked immunosorbent assay. Statistical analyses were performed using a software program, and P values

OBJECTIVE: Central obesity and sub-clinical inflammation increase metabolic risk, this study examined the intracellular inflammatory pathways in adipose tissue (AT) that contribute to this risk. DESIGN AND METHODS: This study therefore addressed the influence of NFκB and JNK activation in human abdominal subcutaneous (AbdSc) and omental (Om) AT, the effect of adiposity, T2DM status and the role of TNFα in vitro, using molecular biology techniques. RESULTS: Our data showed NFκB activity is increased in Om AT versus AbdSc AT (P

Background Visceral Adiposity Index (VAI) is a gender-specific mathematical index estimated with the use of simple anthropometric (body mass index and waist circumference) and biochemical (triglycerides and high density lipoprotein cholesterol) parameters. Recent studies have shown that VAI reflects accurately the degree of visceral adiposity and insulin resistance. However, up to now, VAI has not been evaluated if it correlates with carbohydrate metabolism disorders, as well as with adipokine secretion from the fat mass. Methods In a cohort of 308 out of 414 adult Saudi subjects screened for the study, detailed personal medical history, anthropometrics and metabolic/hormonal profiles were obtained. Additionally, the circulating concentrations of several circulating adipokines, namely adiponectin, leptin, tumour necrosis factor-α (TNF-α) and resistin, were measured. Results Stepwise multivariate analysis showed that VAI was the sole determinant of adiponectin levels (R2 = 0·07, beta ± SE: −0·25 ± 0·05), while BMI and female gender predicted leptin levels (R2 = 0·26, 0·10 ± 0·01 and 0·61 ± 0·15, respectively). Furthermore, the presence of impaired fasting glucose (IFG)/diabetes was predicted only by age and VAI. Conclusions We report for the first time the direct relations of VAI with adipose tissue secretion, as well as with functional glycaemic disorders. Because VAI is estimated easily with data obtained in everyday practice, it could be used as an indirect index of adiponectin levels and the risk of impaired glucose metabolism.

The role of vitamin D in maintaining calcium homoeostasis and bone mineralization is well-established. The aim of the current investigation was to evaluate the effect of calcitriol treatment on inflammation, insulin resistance and liver changes induced by increased body-weight. Four groups of mice (n = 11 each) were maintained on either low-fat diet (LFD) or high-fat diet (HFD) with and without 1α, 25-dihydroxyvitamin D3 (calcitriol) for 16 weeks. Body-weight of animals was recorded at the start of the study and every 4 weeks thereafter. At the end of the experiment, blood samples were collected for the determination of biochemical parameters, and liver tissues were harvested for the histopathological evaluation. A significant gradual decrease in weight was observed in HFD-fed mice treated with calcitriol compared with a steady increase in controls (p

Purpose Seasonal variations in circulating vitamin D levels provide vital information as to the most appropriate time to either start or increase vitamin D supplementation to maintain optimal vitamin D levels. In this follow-up study, we determined seasonal differences in serum 25(OH)-vitamin D (25(OH)D) levels, as well as parallel changes in metabolic parameters, in a cohort of adult, overweight and obese Saudis. Methods A total of 121 adult, overweight, obese, and consenting Saudis aged 18–70 years were randomly recruited from four Primary Health Care Centers in Riyadh, Saudi Arabia. They were divided according to the season when baseline measurements were made [74 summer (April–October); 47 winter (November–March)]. Anthropometrics were obtained, and fasting blood samples were taken at baseline and every 3 months for 1 year. Fasting blood glucose, corrected calcium levels, and lipid profiles were measured routinely. Serum 25(OH)-vitamin D was quantified using a specific enzyme-linked immunosorbent assay (ELISA). Results Age- and BMI-matched mean 25(OH)-vitamin D levels from the winter group were significantly higher than those of the summer group (P < 0·001). In both groups, HDL-C levels improved significantly as 25(OH)-vitamin D levels increased with subsequent follow-ups, even after adjusting for age, gender and BMI (P < 0·001). Conclusion Seasonal differences in serum 25(OH)-vitamin D levels in Saudi Arabia are counterintuitive, with circulating levels being higher during the winter than the summer season. Increased vitamin D supplementation is thus recommended to maintain optimal serum 25(OH)-vitamin D levels during the summer season.

Eur J Clin Invest 2011; 41 (9): 987–994 Abstract Background Prostate disease incidence is expected to rise among developing nations secondary to increased prevalence of obesity and the elderly. Although many case–control studies have associated obesity to prostate cancer aggressiveness, few have correlated markers of prostate pathology to biomarkers of visceral obesity and insulin resistance, using an apparently healthy cohort. This study aims to fill this gap. Materials and methods The 219 consenting adult Arab men, aged 30–70 years, were included in this cross-sectional study. Demographics were noted and anthropometrics measured. Fasting blood samples were extracted, and glycaemic and lipid profile were determined using routine laboratory methods. Serum adipocytokines and inflammatory markers were measured using multiplex assays. Total prostate-specific antigen (tPSA), free PSA (fPSA), parathyroid-related protein (PTHrP) and endoglin were measured using enzyme-linked immunosorbent assays. Results Serum triglycerides and waist–hip ratio (WHR) were significantly and positively associated with circulating (tPSA) levels in all subjects (P

The burning of incense is an important source of indoor air pollution in Asia. We assessed the effect of long-term exposure to incense smoke on the body weight and levels of circulating glucose, triglycerides, total cholesterol, HDL-cholesterol, insulin, adiponectin and leptin in Wistar albino rats. Two groups of rats were used. First group (n = 12) was exposed daily to incense smoke for 4 months at the rate of 4 g day−1 in the exposure chamber. Another group of rats (n = 12), was used as non-exposed control. Blood samples were collected from all animals after 4, 8, 12 and 16 weeks of exposure. Serum glucose, triglycerides, total cholesterol and HDL-cholesterol, LDL-cholesterol insulin, adiponectin and leptin were measured. Our results showed that incense smoke exposure was associated with decreased weight gain and the adverse metabolic changes of increased triglycerides and decreased HDL-cholesterol concentrations. Exposure to incense was also associated with a transient increase of leptin levels. Taken together, these data suggest that incense smoke influences metabolism adversely in rats. The effect of incense smoke on human health and the underlying mechanisms need to be studied further. Copyright © 2011 John Wiley & Sons, Ltd.

Eur J Clin Invest 2010; 40 (12): 1063–1066 Abstract Background Epidemiological studies have suggested an increased prevalence of metabolic syndrome (MS) among adults in the Middle-East. This study aims to determine the prevalence of MS in a large cohort of Saudi children and adolescents. Materials and methods In this cross-sectional observational study, a total of 1231 randomly selected Saudi children and adolescents aged 10–18 years were recruited. Subjects’ information was generated from a database of more than 10 000 Saudi citizens from the existing Biomarkers Screening in Riyadh Program (RIYADH Cohort), Saudi Arabia. Anthropometrics included body mass index, blood pressure, as well as waist and hip circumferences. Fasting blood glucose and lipid profile were determined using routine laboratory procedures. The modified definition of ATP-III (NHANES III) was used for the diagnosis of MS. Results Overall prevalence of complete MS was 9·4% [confidence interval (CI) 7·8–11·0]. Age-adjusted prevalence according to the European standard population is 5·8%. Boys had a comparable MS prevalence with girls [10·3% (CI 8·2–12·4) vs. 8·1% (CI 5·7–10·5), respectively (P = 0·20)]. Low HDL-cholesterol was the most prevalent of all MS risk factors, affecting 86% (CI 85·0–88·6) and hypertriglyceridemia, the second most prevalent, affecting 33% (CI 30·6–35·8) of the subjects. Conclusions The prevalence of MS manifestations among Arab children is extremely high, with dyslipidemia being the most common MS abnormality. Screening for dyslipidemia among Saudi children is warranted especially among those most at risk. Scientific inquiry into the molecular causes of these manifestations should be pursued as a first step in the discovery of aetiological therapies.

Background: Association of resistin with insulin resistance (IR) in humans is still controversial and few studies have investigated the association of plasminogen activator inhibitor-1 (PAI-1) with IR in children. The purpose of the present study was therefore to evaluate serum levels of resistin and active PAI-1 (aPAI-1) in Saudi children and their association with the various obesity-related complications. Methods: In this cross-sectional study, 73 boys and 77 girls with varying body mass index (BMI) were recruited. They were assessed for anthropometric measures and fasting serum levels of glucose, insulin, lipid profile, resistin, angiotensin II (ANG II) and aPAI-1. Results: Resistin was positively correlated with hips (r = 0.33, P

adiponectin;type 2 diabetes;central obesity;HDL cholesterol;ethnicity Aims: Adiponectin is a 30-kDa protein secreted by adipose tissue. The aim of the present study was to compare serum adiponectin in male Indo-Asian and Caucasian subjects and examine its association with fat topography and metabolic parameters. Methods: Diabetic and non-diabetic male subjects (n = 48) were studied. A single observer carried out blood pressure and anthropometric measurements. Serum glucose, insulin, lipid profile and adiponectin (measured by RIA) were measured on a fasting sample. Results: There was no statistically significant difference in serum adiponectin between diabetic and BMI-matched non-diabetic subjects. However, serum adiponectin was lower in Indo-Asians compared with BMI-matched Caucasians, [median adiponectin (interquartile range) 3.3 (2.1–3.9) vs. 4.9 (3.5–6.6) μg/ml respectively (p = 0.016)]. Univariate analysis showed serum adiponectin to be positively associated with HDL in diabetic (p = 0.039) and non-diabetic subjects (p = 0.0098). Waist circumference (p = 0.02), saggital diameter (p = 0.04) were negatively correlated with serum adiponectin in diabetic subjects. Multiple regression analysis including waist, HDL, fasting insulin, age, diabetes and ethnicity in all subjects showed HDL to be the best predictor of serum adiponectin. Conclusions: Serum adiponectin is associated with HDL cholesterol and central obesity. Caucasians have higher serum adiponectin levels compared with Indo-Asians. Further studies are needed to explore basis for the association of adiponectin with HDL cholesterol and the reason for lower levels in Indo-Asians.

Background: The objective of this study was to determine the effect of vitamin D3 supplementation in a cohort of Saudi DMT2 population on diet, insulin and/or different oral hypoglycemic agents and...