Synthesis of New Formyl Halo N-methylimidazole Derivatives

Bromo-formyl imidazoles 16-20 have been prepared by three different ways. The first consisted of conversion of bromo or iodo imidazoles 1-6 into diethyl acetals 13-15, and subsequent hydrolysis into formyl derivatives 7-9. In the second, bromination of. formyl imidazoles with NBS afforded compounds 16-18 in 45-70°/o yield. The third method used direct formylation of bromo imidazoles 10-12 with n-BuLi/DMF reagent into compounds 16, 19, and 20

The pre-analytical stability of 25-hydroxyvitamin D: storage and mixing effects

Background: There is an increasing demand for serum 25-OH VitD testing globally and this has led to the greater use of automated immunoassays. These may be more prone to nonspecific interference, that is thought to be related to pre-analytical stability of biological samples. We have investigated the changes in serum 25-OH VitD concentrations that are caused by storage and mixing conditions, and if such changes are statistical, or clinically important. Methods: Blood samples were collected into plain tubes from 31 healthy donors. After separation, serum samples were stored at -20C° and analysis was carried out with and without mixing (vortexing) at different time intervals of days (0,1,2,3,4,5,15, and 30). All samples were analyzed using a chemiluminescent immunoassay. Results: Mean serum 25-OH VitD concentrations for subsequent days of storage compared to day 0 showed a significant time effect (p< 0.05) except for the samples on day 1 (p=0.654) in non-vortexed samples and day 2 (p=0.087), 5 (p=0.118) and 30 (p=0.118) in vortexed samples. Comparing values for vortexed and non-vortexed samples on the same day, serum 25-OH VitD showed a significant difference on days 1 (p=0.003), 4 (p=0.037), 5 (p=0.002) and 30 (p=0.025). However, the maximum change value was 8.85% which was less than the known total allowable error (TEa) and reference change value (RCV) for serum 25-OH VitD. Conclusion: 25-OH VitD is pre-analytically stable after long-term sample storage at -20°C and can be analyzed without vortexing. This may be beneficial for both research and diagnostic laboratories

Dysglycemia risk score in Saudi Arabia: A tool to identify people at high future risk of developing type 2 diabetes

Abstract Aims/Introduction To develop a non-invasive risk score to identify Saudis having prediabetes or undiagnosed type 2 diabetes. Methods Adult Saudis without diabetes were recruited randomly using a stratified two-stage cluster sampling method. Demographic, dietary, lifestyle variables, personal and family medical history were collected using a questionnaire. Blood pressure and anthropometric measurements were taken. Body mass index was calculated. The 1-h oral glucose tolerance test was carried out. Glycated hemoglobin, fasting and 1-h plasma glucose were measured, and obtained values were used to define prediabetes and type 2 diabetes (dysglycemia). Logistic regression models were used for assessing the association between various factors and dysglycemia, and Hosmer?Lemeshow summary statistics were used to assess the goodness-of-fit. Results A total of 791 men and 612 women were included, of whom 69 were found to have diabetes, and 259 had prediabetes. The prevalence of dysglycemia was 23%, increasing with age, reaching 71% in adults aged ≥65 years. In univariate analysis age, body mass index, waist circumference, use of antihypertensive medication, history of hyperglycemia, low physical activity, short sleep and family history of diabetes were statistically significant. The final model for the Saudi Diabetes Risk Score constituted sex, age, waist circumference, history of hyperglycemia and family history of diabetes, with the score ranging from 0 to 15. Its fit based on assessment using the receiver operating characteristic curve was good, with an area under the curve of 0.76 (95% confidence interval 0.73?0.79). The proposed cut-point for dysglycemia is 5 or 6, with sensitivity and specificity being approximately 0.7. Conclusion The Saudi Diabetes Risk Score is a simple tool that can effectively distinguish Saudis at high risk of dysglycemia.Peer reviewe

Association Between Anthropometric Indices and Nonanthropometric Components of Metabolic Syndrome in Saudi Adults

Context: Waist circumference (WC) is used in screening for metabolic syndrome (MetS) based on its association with cardiometabolic risk.This might apply differently in ethnically different populations. Associations with other measures are also unclear. Objective: This work aimed to investigate the association between neck circumference (NC), WC, WC:hip circumference, WC:height (VVC:Ht), NC:Ht, fat percentage, body mass index (BMI), conicity index, abdominal volume index, and weight-adjusted waist index with nonanthropometric components of MetS in nondiabetic Saudi adults. Methods: This cross-sectional study took place in public health centers in Jeddah, comprising 1365 Saudi adults (772 men and 593 women) aged 18 years or older not previously diagnosed with diabetes. Main outcome measures included the presence of 2 or more nonanthropometric components of the MetS were used to define clinical metabolic abnormality (CMA). The predictive ability of studied anthropometric indices for CMA was determined using the area under receiver operating characteristics (AUC) curve and binary logistic regression. Results: A total of 157 men and 83 women had CMA. NC and NC:Ht had the highest predictive ability for CMA in men (odds ratio [OR](NC) = 1.79, P < .001 and ORNC:Ht = 1.68, P < .001; AUC(NC) = 0.69 [95% CI, 0.64-0.74] and ALS, = 0.69 [95% CI, 0.64-0.73]). In women, WC had the highest predictive ability ORWC = 1.81, P< .001; AUC(WC) = 0.75 [95% CI, 0.69-0.80]). Conclusion: Upper-body anthropometric indicators that were associated with subcutaneous fat had the highest predictive ability for CMA in men whereas abdominal obesity indictors had the best predictive ability in women, suggesting that fat distribution might contribute to CMA in a sex-specific manner.Peer reviewe

The association between hypertension and other cardiovascular risk factors among non-diabetic Saudis adults-A cross sectional study

Population specific associations between cardiovascular disease with various risk factors including pre-hypertension and hypertension were reported. We aimed to investigate the association of higher than optimal blood pressure with measures of dysglycemia, dyslipidemia, and markers of inflammation in non-diabetic Saudi adults hoping to improve current Saudi guidelines to prevent cardiovascular disease. Volunteers were recruited randomly from public healthcare centers in Jeddah. Demographic information, blood pressure (BP), and anthropometric measurements were taken. Fasting blood samples were drawn, then again following 1-hour oral glucose tolerance test. Glycated hemoglobin, fasting plasma glucose (FPG), lipid profile, highly sensitive C- reactive protein, gamma glutamyl transferase, and 1-hour plasma glucose were measured. Complete data was found for 742 men and 592 women. Pre-hypertension was found in 47.2% of men, and 24.7% of women, while 15.1% of men, and 14.6% of women were hypertensive. Means of measured variables differed significantly between normotensive, pre-hypertensive, and hypertensive groups of men and women in gender specific manner. Association between measured variables and elevated BP, and hypertension were assessed using logistic regression models. After adjustment for age, body mass index and waist circumference, elevated blood pressure was associated with elevated triglycerides in men, while hypertension was significantly associated with elevated fasting plasma glucose, total cholesterol, triglycerides, low density lipoprotein- cholesterol, and low high density lipoprotein- cholesterol in men, and elevated triglycerides, and total cholesterol in women. Therefore, it is strongly recommended to measure lipid profile, specifically TG, for all diagnosed pre-hypertensive and hypertensive patients in addition to FPG for men.Peer reviewe

Stability and validity of intact parathyroid hormone levels in different sample types and storage conditions

Background Several pre-analytical factors can affect the measurement of intact Parathyroid Hormone (IPTH). In this study, we have investigated the effects of using different types of tubes, time elapsed before separation, and storage conditions over time on the measured values of IPTH. Method Blood samples from 30 subjects were collected into plain, SST, and EDTA tubes. All serum and plasma were separated immediately (first set) and after 2 hrs delay (second set). The first set of samples were aliquoted and stored at RT (25°C), at fridge (4°C), and freezer (−20°C). IPTH was measured in all the stored aliquots at 2,4, and 8 days after collection using Architect analyzer. Results Paired T test and ANOVA repeated measures showed no significant difference between IPTH levels in all tubes. The second set of serum and plasma were significantly lower (3.8% and 7.4%, p < 0.001, respectively) when compared to samples measured initially. Serum samples stored at RT were significantly lower (by 45%,59%, and 77%) on days 2,4, and 8 when compared to the initial time (p < 0.001 in all cases). Plasma samples stored at RT, were significantly lower on day 8 after collection, by 30.8% (p < 0.001). These differences would be clinically important. Conclusion Plasma IPTH can be stored at RT for up to four days. Both plasma and serum IPTH are not affected by a delay in the separation of up to two h and they can be stored for up to 8 days in a fridge or freezer without any clinically significant changes in their values

Selection of the appropriate method for the assessment of insulin resistance

Insulin resistance is one of the major aggravating factors for metabolic syndrome. There are many methods available for estimation of insulin resistance which range from complex techniques down to simple indices. For all methods of assessing insulin resistance it is essential that their validity and reliability is established before using them as investigations. The reference techniques of hyperinsulinaemic euglycaemic clamp and its alternative the frequently sampled intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance. However, many simple methods, from which indices can be derived, have been assessed and validated e.g. homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI). Given the increasing number of simple indices of IR it may be difficult for clinicians and researchers to select the most appropriate index for their studies. This review therefore provides guidelines and advices which must be considered before proceeding with a study

Reference change values for insulin and insulin-like growth factor binding protein-1 (IGFBP-1) in individuals with varying degrees of glucose tolerance

Background. The reference change value (RCV) is an important parameter of biological variation used to assess the significance of differences between consecutive results obtained in a single individual. This study evaluated the RCV for insulin-like growth factor binding protein-1 (IGFBP-1) and fasting serum insulin (FSI) in individuals with different degrees of glucose tolerance. Methods. IGFBP-1 and FSI concentrations were measured in 33 fasting subjects who had two blood samples taken 10 days apart. Subjects were distributed in the following categories: Normal glucose tolerance (NGT), n = 15, impaired fasting glucose (IFG), n = 9 and impaired glucose tolerance (IGT), n = 9. Results. The RCV values for IGFBP-1 were 59.9%, 83.2% and 93.0% and for FSI were 68.5%, 79.0% and 93.4% for subjects with NGT, IFG and IGT respectively. Conclusions. The RCVs for IGFBP-1 and FSI increase with deteriorating glucose tolerance. When monitoring IGFBP-1 and FSI, changes in concentrations should be interpreted using glycaemic category-specific RCV values

Serum insulin-like growth factor binding protein-1: an improvement over other simple indices of insulin sensitivity in the assessment of subjects with normal glucose tolerance

BACKGROUND Insulin resistance is associated with an increased risk of cardiovascular disease and diabetes. It can be assessed using complex reference techniques, such as clamp or frequently sampled intravenous glucose tolerance test (FSIVGTT). Therefore, simple indices derived from fasting insulin and glucose concentrations have been proposed. The aim of this study is to assess fasting serum insulin-like growth factor binding protein-1 (IGFBP-1) as a simple index of insulin sensitivity compared with other simple indices and FSIVGTT. METHODS Fasting serum IGFBP-1, fasting plasma insulin (FPI), homeostasis model assessment (HOMA-IR), quantitative insulin check index (QUICKI), fasting glucose to insulin ratio (FGIR), Raynaud and insulin glycaemic index (ISI-gly) were correlated with FSIVGTT (Si) in 22 subjects with normal glucose tolerance (NGT) and nine with impaired fasting glucose (IFG). RESULTS In NGT individuals, IGFBP-1 correlated more strongly with Si than did any other index both before (r = 0.76) and after (r = 0.79) natural logarithm (ln) transformation. In subjects with IFG, IGFBP-1 was weakly correlated with Si before and after ln-transformation (r = 0.55, r = 0.56, respectively), but ISI-gly was the index most strongly correlated with Si (r = 0.77, r = 0.85, respectively). CONCLUSIONS In subjects with NGT, fasting serum IGFBP-1 could be used as a simple reliable marker of insulin sensitivity. For more accurate estimation of insulin sensitivity in normal subjects and those with IFG, ln-transformation is preferred over raw dat