Bone metabolism markers are associated with neck circumference in adult Arab women.

The study aimed to determine whether neck circumference is associated with bone metabolism markers among adult Arab women and found modest but significant associations with bone resorption markers, suggesting that neck circumference, a surrogate measure of upper subcutaneous fat, influences bone turnover expression among adult females. INTRODUCTION: Body fat distribution is associated with decreased bone resorption and neck circumference (NC), a surrogate measure for upper body fat, has never been tested as a marker that can reflect bone turnover. This is the first study aimed to analyze the associations between NC and several bone biomarkers among adult Saudi women. METHODS: This cross-sectional study included a total of 265 middle-aged Saudi women [86 non-obese (mean age 52.7 ± 8.1; mean BMI 26.9 ± 2.3) and 179 obese (mean age 50.6 ± 7.5; mean BMI 35.7 ± 4.5)] recruited from primary care centers in Riyadh, Saudi Arabia. Anthropometrics included BMI, NC, waist and hip circumferences, total body fat percentage (%), and blood pressure. Biochemical parameters included glucose and lipid profile which were measured routinely. Serum levels of 25(OH) D, parathyroid hormone, RANKl, sclerostin, C-terminal telopeptide of collagen I (CTX-I), Dkk1, IL1ß, osteoprotegerin, osteopontin, and osteocalcin were measured using commercially available assays. RESULTS: In all groups, NC was inversely associated with PTH (R = - 0.22; p < 0.05) and positively associated with osteoprotegerin (R = 0.20; p < 0.05) even after adjustments for age and BMI. Using all anthropometric indices as independent variables showed that only NC explained the variance perceived in CTX-I (p = 0.049). In the non-obese, waist-hip ratio (WHR) was significantly associated with sclerostin (R = 0.40; p < 0.05) and body fat was significantly associated with osteopontin (R = 0.42; p < 0.05). CONCLUSION: NC is modestly but significantly associated with bone biomarkers, particularly the bone resorption markers, among adult Arab women. The present findings highlight the importance of NC as measure of upper body subcutaneous fat in influencing bone biomarker expression in adult females.

Serum 25-hydroxyvitamin D status among Saudi children with and without a history of fracture.

BACKGROUND: The significance of vitamin D deficiency in the incidence of bone fractures in children has been under investigated. Here, we aimed to associate serum 25-hydroxyvitamin D levels and fractures in Saudi children. MATERIALS AND METHODS: This cross-sectional study was conducted in 1022 Saudi children without fracture history [476 boys (age 14.56 ± 1.81, BMI 22.38 ± 5.81) and 546 girls (age 13.57 ± 1.67, BMI 22.24 ± 4.94)] and 234 Saudi children with a history of fracture [148 boys (age 14.25 ± 1.39, BMI 22.66 ± 6.08) and 86 girls (age 13.76 ± 1.35, BMI 21.33 ± 1.35)]. Anthropometric and fasting serum biochemical data were collected. Serum 25-hydroxyvitamin D level was assessed using electrochemiluminescence. RESULTS: Mean circulating 25-hydroxyvitamin (25OH) D level in subjects with a history of fracture was significantly lower in both boys (p < 0.01) and girls (p < 0.01) than those without, however both groups had low mean 25(OH)D levels. Furthermore, age was positively associated with 25-hydroxyvitamin D in boys (p < 0.05) and negatively in girls (p < 0.05) with a history of fracture. CONCLUSION: In conclusion, vitamin D levels were significantly lower in children with a history of bone fractures in both boys and girls than those without such a history; even in the absence of fracture history, vitamin D status correction is warranted in the general Saudi pediatric population.

Comparisons in childhood obesity and cardiometabolic risk factors among urban Saudi Arab adolescents in 2008 and 2013.

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 < 0.001]. The age groups 13 and 15 years had a significantly higher mean triglycerides in 2013 than 2008 (P-values 0.003 and <0.001, respectively) and lower mean HDL-cholesterol also in the 13 years old age group (P < 0.001). CONCLUSIONS: The prevalence of childhood obesity in Saudi Arabia has increased in particular age groups (13-15 years) during a 5-year span. Special attention is warranted in these vulnerable age groups, particularly in boys, as cardiometabolic risk factors appear to worsen.

Exposure to difenoconazole, diclofop-methyl alone and combination alters oxidative stress and biochemical parameters in albino rats.

The herbicides diclofop-methyl and the fungicide difenoconazole are widely used in agriculture and may lead to serious toxicity risks. However, limited studies have been done to evaluate differences in the metabolic effects of these herbicides. Difenoconazole (10 mg/kg) and Diclofop-methyl (1 mg/kg) were orally administrated individually (Groups 1 and 2 respectively) as well as combined (G3) to rats for 28 days. In all treated groups, alanine aminotransferase (ALT) and urea were significantly higher than the control group. Plasma creatinine was also significantly higher in groups G1 and G2 than control. Significant inhibition in gamma glutamyltransferase (γGT) was observed in all treated groups, in addition to significant inhibition of plasma acetylcholinesterase enzyme (AChE) in G3 (p < 0.01). There was no effect in aspartate aminotransferase (AST) and albumin. Total plasma triiodothy-ronine (T3) hormone was significantly higher in groups G2 and G3 (p < 0.01), but significantly lower in G1 group as compared to control. Thyroxin (T4) was significantly lower in all treated groups than control. Cholesterol level was significantly lower in G3 than control, and a total protein (TP) was significantly higher in all treated groups than control. No differences were observed in glucose levels. Malondialdehyde (MDA) and superoxide dismutase (SOD), an oxidative stress biomarker, was significantly increased in all treated groups comparing to control. Sulphur containing protein (SH-protein) was significantly lower in G1 than control. No significant changes were observed for GST in all treatments. The significant differences in measured biomarkers after application of diclofop-methyl, difenoconazole individually and combined indicate that the investigated pesticides may have potentially harmful effects on humans and the surrounding environment. We suggest that larger studies be conducted to better understand the toxicity mechanisms of these pesticides.

Normal circulating PTH in Saudi healthy individuals with hypovitaminosis D.

Recent studies in the Middle East have shown an increased incidence of vitamin D deficiency across this region of year-round sunlight. There is scarcity of information, however, as to the levels of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of vitamin D, and its associations with cardiometabolic parameters in an Arab cohort and this study aims to fill this gap. In a cross-sectional study, 33 male and 43 female (22 children and 54 adults, total 76) Saudis with previously established low levels of serum 25-hydroxyvitamin D [25(OH)D] (<50 ng/ml or 20 nmol/l) were recruited. Anthropometrics were obtained and fasting blood samples were taken for a routine measurement of glucose, lipid profile, calcium, and albumin, while serum 25(OH)D, 1,25-(OH)2D, and intact PTH were quantified using specific ELISAs. Serum calcium, intact PTH, and 1,25(OH)2D were all within the normal range in both children and adults in both genders. In all subjects, serum 1,25(OH)2D was not associated with intact PTH, while circulating 1,25(OH)D inversely correlated with systolic blood pressure (p=0.01) and waist circumference (p=0.04). Thus, vitamin D deficient Saudi children and adults with normal levels of 1,25-(OH)2D also had normal circulating calcium and PTH. This study suggests that local cutoffs should be set that will be of clinical significance in the identification of those at true risk for harder end-points, such as secondary hyperparathyroidism and bone-related diseases.

Hypovitaminosis D associations with adverse metabolic parameters are accentuated in patients with Type 2 diabetes mellitus: a body mass index-independent role of adiponectin?

BACKGROUND: Hypovitaminosis D has been associated with an increased prevalence of Type 2 diabetes mellitus (DMT2) and metabolic syndrome manifestations. The purpose of this study was to examine the association between 25-hydroxy-vitamin D (25-OH-VitD) levels and indices of insulin resistance (IR), including adipocytokines, in a Saudi population with or without DMT2. SUBJECTS AND METHODS: A total of 266 subjects (153 DMT2 and 113 healthy controls) aged 26-80 yr were randomly selected from the existing Biomarkers Screening in Riyadh Program (RIYADH Cohort). Subjects were assessed clinically, anthropometry was performed, morning blood chemistries, including fasting glucose (FG), triglycerides, total cholesterol, LDL cholesterol (LDL-C), and HDL cholesterol were obtained. Homeostasis model assessment of IR (HOMA-IR) was calculated, and serum 25-OH-VitD, leptin, adiponectin, resistin, insulin, high sensitivity CRP (hsCRP), and tumor necrosis factor α concentrations were measured using specific assays. RESULTS: In DMT2 subjects, negative correlations between 25-OH-vitD and body mass index (BMI), FG, insulin, HOMA-IR, cholesterol, LDL-C, and hsCRP were observed, while a positive correlation between 25-OH-VitD and adiponectin was detected. The later remained significant after controlling for BMI. Interestingly, only weak and nonsignificant associations between 25-OH-VitD and metabolic parameters were observed in the control group, whereas, when the entire population was examined, negative correlations were evident primarily between 25-OH-VitD and FG, HOMA-IR, total cholesterol, LDL-C. These associations remained significant after controlling for BMI. CONCLUSIONS: These results suggest that hypovitaminosis D associations with metabolic disturbances are accentuated in DMT2. The BMIindependent positive correlation between 25-OH-VitD and adiponectin suggests a potential role for this adipocytokine as a link between 25-OH-VitD and IR in patients with DMT2.

Urinary iodine is associated with insulin resistance in subjects with diabetes mellitus type 2.

BACKGROUND: Diabetes Mellitus (DM) is a major health problem worldwide and its prevalence in Saudi Arabia has reached 31.6%. Patients with diabetes mellitus are at an increased risk of thyroid disease. The purpose of this study was to examine the urinary excretion of iodine in type 2 DM (T2DM) patients, and to assess the clinical implication of iodine status on T2DM. METHODS: A total of 266 adult Saudis aged 18-55 years (109 T2DM patients and 157 healthy controls) were randomly selected from the Riyadh Cohort Study. Subjects were assessed for anthropometry, morning blood chemistries including fasting glucose, and lipid profile; serum concentrations of leptin, adiponectin, resistin, insulin, aPAI, hsCRP, Ang II, TNF-α, TSH, T3, T4, urine creatinine, urine iodine were measured using specific assays. RESULTS: The concentration of urine iodine was significantly lower in T2DM than in healthy control subjects (84.6±2.3 vs. 119.4±3.4, p<0.001), which remained significant after creatinine correction and controlling for age (p=0.01). Furthermore, urinary iodine is negatively correlated with waist, hips, SAD, glucose, insulin, HOMA-IR triglyceride, resistin, angiotensin II (Ang II), and CRP, while it was positively associated with TSH. CONCLUSIONS: The decreased levels of iodine concentration in T2DM patients and its likely deleterious effects on metabolic functions calls for a systematic approach to thyroid disease screening in diabetic patients. Routine annual urinary iodine determination is recommended and should target T2DM patients at risk of thyroid dysfunction.

Blood thiamine and its phosphate esters as measured by high-performance liquid chromatography: levels and associations in diabetes mellitus patients with varying degrees of microalbuminuria.

BACKGROUND: Thiamine deficiency has been linked to microvascular complications in patients with diabetes mellitus (DM). In this study, we aim to assess blood and urine thiamine status by high performance liquid chromatography (HPLC) in patients with DM Type 1 and Type 2 (DMT1, DMT2) and to identify associations with markers of incipient nephropathy and kidney dysfunction. SUBJECTS AND METHODS: A total of 205 subjects (43 DMT1 and 162 DMT2) with and without microalbuminuria and 26 non-diabetic controls were included. Fasting blood samples were collected and anthropometric parameters were measured. Fasting blood, lipid and renal profile were determined routinely. Blood thiamine concentration, its phosphate esters and urine thiamine were quantified using HPLC. RESULTS: Blood thiamine concentrations (ng 1-1) were decreased by 75.7% and 49.6% in patients with DMT1 and DMT2, respectively [controls (54.8+/-11.4); DMT1 (41.5+/-17.9); DMT2 (27.2+/-12.7), p<0.001]. Among those with normo-albuminuria, urinary excretion of thiamine was significantly increased to 390.1 microg/ml and 1212.4 microg/ml in DMT1 and DMT2 respectively, as compared to controls (326.4 microg/ml). DMT1 and DMT2 patients with micro- albuminuria on the other hand had 2.5- and 3.4-fold increase in urinary excretion of thiamine compared to controls. CONCLUSION: Low levels of blood thiamine are present in patients with DMT1 and DMT2, and are associated with increased thiamine clearance.

Gender-specific associations between insulin resistance, hypertension, and markers of inflammation among adult Saudis with and without diabetes mellitus type 2.

PURPOSE: In view of the important roles of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and the acute phase reactant C-reactive protein (CRP) in glucose metabolism and pathogenesis of diabetes mellitus type 2 (DMT2), we assessed gender-specific differences and relative associations of these inflammatory biomarkers to insulin resistance (IR) and risk markers for DMT2. MATERIALS AND METHODS: Serum levels of TNF-α, IL-6 and CRP were determined in 119 clinically diagnosed DMT2 cases, 114 non-DMT2 subjects with IR, and 97 age-matched controls. Fasting blood samples were collected and serum glucose levels, lipid profile, and inflammatory markers were analyzed. RESULTS: In women, a significant association between elevated levels of IL-6 and risk of developing IR [Odds ratio (OR), 4.389, 95 % Confidence Interval (CI) 1.6-11.52, p = 0.004] was found. Significant associations were also found between elevated levels of CRP and risk of hypertension only in female subjects [OR (95% CI) 2.153 (1.04-4.53), p = 0.046]. While, in male subjects, a significant association between elevated levels of TNF-α and risk of developing IR [OR (95% CI) 2.32 (1.09-4.93), p = 0.029] was found. CONCLUSION: The present study showed apparent gender differences in the association of IL-6, CRP, and TNF-a with risks of IR and hypertension, and this could be attributed to sexual dimorphism in fat distribution.

Telomere length in relation to insulin resistance, inflammation and obesity among Arab youth.

AIM: The aim of this study was to determine the associations of telomere length to markers of obesity, insulin resistance and inflammation in Saudi children. METHODS: A total of 69 boys and 79 girls, aged 5-12 years, participated in this cross-sectional study. Anthropometrics were measured. Serum glucose and lipid profile were measured using routine laboratory methods. Serum insulin, leptin, adiponectin, resistin, tumour necrosis factor-alpha and active plasminogen activator inhibitor 1 were quantified using customized multiplex assay kits. C-reactive protein and angiotensin II were quantified using ELISA. Leucocyte telomere length was examined by quantitative real time PCR utilizing IQ cycler. RESULTS: Mean telomere length was significantly shorter in obese boys compared with their lean counterparts (p = 0.049), not in girls. It was not associated to insulin resistance, adipocytokines and markers of inflammation. In girls, the significant predictor of telomere length was waist circumference, explaining 24% of variance (p = 0.041) while in boys, systolic blood pressure explained 84% of the variance (p = 0.01). CONCLUSION: Childhood obesity in boys corresponds to shorter leucocyte telomere length which is not evident in girls. The association of leucocyte telomere length to blood pressure and waist circumference in children suggests clinical implications as to the contribution of these parameters in premature ageing.

Bioequivalence of Jusline following subcutaneous administration in healthy subjects.

OBJECTIVE: The aim of the current work is to evaluate the pharmacokinetic and pharmacodynamic profile of a new human insulin preparation (jusline) following subcutaneous administration in healthy subjects, and to compare this profile with Humulin insulin. METHODS: 20 healthy male subjects received a single dose of 0.2 U/kg of test (Jusline) or reference insulin (Humulin) during an euglycemic clamp keeping blood sugar constant (90 +/- 5 mg/dl) by changing the glucose infusion rate. Pharmacokinetic and pharmacodynamic measurements were taken from blood measurements of glucose, insulin, and C-peptide levels for tested insulin formulations. RESULTS: The mean values of the individual AUC ratios were well within the 90% confidence interval (100.5% for Regular, 101.9% for NPH, and 100.0% for Premixed Regular/NPH (30/70)). Similarly, Cmax and tmax were within the bioequivalence limit (80 - 125%). The maximum GIR were 10.20 mg/kg/min and 9.72 mg/kg/min for Jusline Regular and Humulin Regular, respectively. The maximum GIR were 7.09 mg/kg/min and 7.91 mg/kg/min for Jusline NPH and Humulin NPH, respectively. The maximum GIR and tGIRmax were 6.39 mg/kg/min and 6.63 mg/kg/ min for Jusline Premixed Regular/NPH (30/70) and Humulin Premixed Regular/NPH (30/70), respectively. Both insulin products produced similar suppression of endogenous C-peptide level (-29.76% to -50.22%). CONCLUSION: The present study demonstrated that after subcutaneous administration, there are no significant differences between Jusline and Humulin to promote peripheral glucose uptake.