Association of Protein Tyrosine Phosphatase Receptor Type D and Serine Racemase Genetic Variants with Type 2 Diabetes in Malaysian Indians.

Introduction: Type 2 diabetes (T2D) candidate genes, protein tyrosine phosphatase receptor type D (PTPRD), and serine racemase (SRR) were suggested by a genome-wide association study (GWAS) in the Chinese population. Association studies have been replicated among East Asian populations. The association of PTPRD and SRR genetic variants with T2D in Southeast Asian populations still needs to be studied. This study aimed to investigate the association of PTPRD and SSR genetic variants with T2D in Malaysian Indian subjects. Methods: The single nucleotide polymorphisms (SNPs) of PTPRD (rs649891 and rs17584499) and SRR (rs4523957, rs391300, and rs8081273) were genotyped in 397 T2D and 285 normal Malaysian Indian subjects. Results: The homozygous dominant genotype of rs17584499 is frequent in diabetic patients (56.5%) compared to normal subjects (47.3%). In contrast, the homozygous recessive genotype of rs8081273 is more frequent among normal subjects (12.5%) than diabetic patients (5.6%). The dominant genetic model showed that PTPRD rs17584499 (CC) is a risk factor for T2D (OR = 1.42, P = 0.029), whereas the recessive genetic model showed that SRS SNP rs8081273 was protective for T2D (OR = 0.42, P = 0.003). Conclusion: This study confirmed the association of PTPRD rs17584499 genetic variations with T2D in Malaysian Indians. While the SRR rs8081273 (TT) genotype showed protection against T2D, more investigation in different populations is required to confirm this protection.

Plasma Lipocalin-2 and Adiponectin are Affected by Obesity Rather Than Type 2 Diabetes Mellitus per se.

PURPOSE: Changes in plasma adipocytokines and inflammatory markers in type 2 DM remain controversial as to whether they are due to obesity or directly associated with the diabetic state. Our objective was to study the effect of obesity and diabetes on plasma lipocalin-2 (LCN2), adiponectin, and interleukin-1ß (IL-1ß) by comparing their levels in non-diabetic obese subjects and non-obese type 2 DM patients, as well as determining the association of these adipocytokines with metabolic syndrome factors and diabetic parameters. PATIENTS AND METHODS: In this study, 85 Yemeni male volunteers aged 30-60 years old were enrolled, 25 of whom were healthy subjects with BMI < 25 kg/m2 served as control; 30 non-diabetic obese subjects (BMI ≥ 30 kg/m2 and FBG < 6.1 mmol/l); and 30 non-obese type 2 DM patients (BMI < 25 kg/m2 and FBG > 7 mmol/l). RESULTS: Lipocalin-2 and adiponectin were significantly (p = 0.043 and p = 0.034) lower in non-diabetic obese subjects by 16.2% and 29.7% with respect to control group, with no effect in the non-obese type 2 DM patients. Moreover, LCN2 was significantly (p = 0.04) lower in the non-diabetic obese subjects by 15.8% as compared with the non-obese type 2 DM patients, with no significant difference in adiponectin levels. In contrast, serum IL-1ß was significantly (p = 0.001 and p = 0.003) higher in both non-diabetic obese subjects and the non-obese type 2 DM patients by 76.5% and 67.7% as compared to control group. The significant decrease in both LCN2 and adiponectin and the significant increase in IL-1ß in the non-diabetic obese subjects disappeared upon adjustment for waist circumference (WC). In contrast, the significant increase in IL-1ß in the non-obese Type 2 DM patients was not affected upon adjustment for WC. CONCLUSION: Plasma LCN2 and adiponectin were not affected by diabetes per se, suggesting that the observed changes in LCN2 and adiponectin in type 2 DM may be due to obesity rather than the diabetic state, whereas IL-1ß levels were affected by both obesity and diabetes.

Latent Autoimmune Diabetes in Adults (LADA) and its Metabolic Characteristics among Yemeni Type 2 Diabetes Mellitus Patients.

PURPOSE: Although there is ample data about the prevalence of diabetes in the Middle East, little is known about the prevalence and features of autoimmune diabetes in this region. The aim of this study was to investigate the prevalence and metabolic characteristics of latent autoimmune diabetes in adults (LADA) amongst Yemeni Type 2 DM patients. PATIENTS AND METHODS: In this cross-section study, 270 Type 2 DM patients aged 30-70 years were recruited from the National Diabetes Center, Al-Thowra Hospital, Sana'a city, during the period November 2015 to August 2016. All Type 2 DM patients were diagnosed within 5 years and who did not require insulin for a minimum of 6 months following diagnosis. Levels of glutamic acid decarboxylase autoantibodies (GADA) were measured in all patients, and LADA was diagnosed in patients testing positive for anti-GAD antibodies. Further, biochemical analysis was carried out including fasting blood glucose (FBG), glycated haemoglobin (HbA1c), insulin, and lipid profile. Insulin resistance (HOMA-IR) and ß-cell function (HOMA-ß) were calculated. RESULTS: The prevalence of LADA, as defined by GADA-positive, amongst patient with Type 2 DM was 4.4%; with no significant difference in the prevalence between male (5.8%) and female (3.4%). LADA patients were younger than GADA-negative Type 2 DM. Body mass index, waist circumference, insulin and HOMA-ß were significantly lower in LADA patients, whereas triglyceride, cholesterol, HDL-c and HOMA-IR were non-significantly lower with respect to Type 2 DM. In contrast, FBG and HbA1c were significantly higher in LADA patients. Moreover, the prevalence of metabolic syndrome was significantly lower in LADA as compared with Type 2 DM. Only 2 out of the 12 GADA-positive (16.7%) were on insulin treatment at the time of the study. CONCLUSION: The prevalence of LADA in Yemeni Type 2 DM is lower than many of those reported in the literature, with no gender preference. Metabolic syndrome was significantly lower in LADA patients. Patients with LADA share insulin resistance with Type 2 DM but display a more severe defect in ß-cell function, thus highlighting the importance of an early diagnosis of LADA, to correctly treat LADA patients, allowing safe and effective therapies.

Impact of triglycerides and waist circumference on insulin resistance and ß-cell function in non-diabetic first-degree relatives of type 2 diabetes.

BACKGROUND: Although there is abundant evidence indicating the relative contribution of insulin resistance (HOMA-IR) and ß-cell dysfunction (HOMA-ß) among first-degree relatives (FDRs) of Type 2 DM patients, few studies reported the association between HOMA-IR and HOMA-ß with metabolic syndrome. Our objective was to evaluate the impact of metabolic syndrome factors on HOMA-IR, HOMA-ß and glycoproteins in non-diabetic FDRs. METHODS: In this study, 103 Yemeni male subjects aged 25-42 years, with BMI < 25 kg/m2 were examined, 39 of whom were normal subjects with no family history of diabetes served as control and 64 subjects were non-diabetic FDRs of Type 2 DM patients. RESULTS: Both glycoproteins, glycated haemoglobin (HbA1c) and fructosamine as well as insulin, HOMA-IR and HOMA-ß were significantly (p = 4.9 × 10-9; 6.0 × 10-8; 6.6 × 10-12; 1.3 × 10-7; 5.5 × 10-12, respectively) higher in non-diabetic FDRs as compared to control group. Fasting plasma glucose, though within normal range, were significantly (p = 0.026) higher in non-diabetic FDRs. Linear regression analysis showed that both TG and WC are the main metabolic syndrome factors that significantly increased HOMA-IR (B = 0.334, p = 1.97 × 10-6; B = 0.024, p = 1.05 × 10-5), HOMA-ß (B = 16.8, p = 6.8 × 10-5; B = 0.95, p = 0.004), insulin (B = 16.5, p = 1.2 × 10-6; B = 1.19, p = 8.3 × 10-6) and HbA1c (B = 0.001, p = 0.034; B = 0.007, p = 0.037). CONCLUSION: Triglyceride and WC are the important metabolic syndrome factors associated with insulin resistance, basal ß-cell function and insulin levels in non-diabetic FDR men of Type 2 DM patients. Moreover, FDRs showed insulin resistance with compensatory ß-cell function (hyperinsulinaemia) suggesting that insulin resistance precede the development of pancreatic ß-cell dysfunction in individuals at risk of Type 2 DM.

Metabolic Syndrome and Prediabetes Among Yemeni School-Aged Children.

PURPOSE: In view of the high rate of obesity and physical inactivity as well as the rising incidence of Type 2 DM among children in the neighboring Gulf countries and Middle East region; the aim of this study was, therefore, to determine the prevalence of metabolic syndrome (MetS) and prediabetes in Yemeni school-aged children. PATIENTS AND METHODS: In this study, 1402 school children aged 12-13 years old (grade 7) were recruited from public schools in the capital Sana'a during the period April-May 2013. Anthropometric measurements and BP were recorded and BMI was calculated. Fasting venous blood (5 mL) was collected for biochemical analysis including FBG, HbA1c, insulin and lipids profile. Insulin resistance (HOMA-IR) and ß-cell function (HOMA-ß) were calculated. RESULTS: The prevalence of prediabetes (as defined by impaired fasting glucose) and MetS (as classified by the IDF 2007) were 0.86% and 0.5%, respectively. Our results also showed 5.21% and 20.26% of the children to have two or one factor(s) of the MetS criteria fulfilled, respectively, with low HDL-c (17%) being the most prevalent MetS component, followed by metabolic glucose (8%), raised TG (5.3%), DBP (1.4%), and high WC (0.5%). Moreover, the prevalence of overweight and obesity was 4.2% and 2.8%, respectively; and about 1.2% of children had abnormal high insulin levels. Children with impaired fasting glucose (IFG) had increased HOMA-IR (p = 0.016) and SBP (p = 0.042) and decreased HDL-c (p = 0.034) and HOMA-ß (p < 0.001); whereas obese children had increased WC (p < 0.001) and TG (p = 0.049). CONCLUSION: The main finding of this study is that Yemeni children are at potential risk of obesity, metabolic syndrome and prediabetes despite their low prevalences. These results highlight the need for early identification and close monitoring of children at risk of later Type 2 DM as an important primary care strategy that can effectively prevent or delay the onset of such condition.

Relationship of metabolic syndrome defined by IDF or revised NCEP ATP III with glycemic control among Malaysians with Type 2 Diabetes.

BACKGROUND: The chronic complications of Type 2 Diabetes (T2D) such as macrovascular disease is amplified with the increase in the number of metabolic syndrome (MetS) risk factors. This research aims to study the relationship of MetS, diagnosed by the International Diabetes Federation (IDF) or revised National Cholesterol Education Programs Adult Treatment Panel III (NCEP ATP III) criteria, with glycemic control, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), C-peptide, and insulin resistance in T2D patients. METHODS: The study is a cross-sectional observational study which, involved 485 T2D patients who are receiving treatment at the University Kebangsaan Malaysia Medical Center (UKMMC), Kuala Lumpur, Malaysia. The MetS among the T2D patients was diagnosed based on IDF and revised NCEP ATP III criteria. C-peptide and HbA1c levels were determined by an automated quantitative immunoassay analyzer and high-performance liquid chromatography, respectively. The MetS factors; FBG, triglyceride, and high-density lipoprotein cholesterol were measured by spectrophotometer. RESULTS: Application of the IDF and revised NCEP ATP III criteria respectively resulted in 73% and 85% of the T2D subjects being diagnosed with MetS. The concordance of these criteria in diagnosing MetS among T2D patients was low (κ = 0.33, P < 0.001). Both IDF and revised NCEP ATP III criteria indicated that T2D patients with 5 MetS factors had higher insulin resistance (P = 2.1 × 10-13; 1.4 × 10-11), C-peptide (P = 1.21 × 10-13; 4.1 × 10-11), FBG (P = 0.01; 0.021), and HbA1c (P = 0.039; 0.018) than those T2D patients without MetS, respectively. CONCLUSION: Although there is a low concordance between IDF and revised NCEP ATP III criteria in the diagnosis of MetS among T2D patients, both criteria showed that T2D patients with 5 MetS factors had higher insulin resistance, C-peptide, FBG, and HbA1c.

Asymptomatic carriage of Streptococcus pyogenes among school children in Sana'a city, Yemen.

OBJECTIVES: Streptococcus pyogenes is the most frequent cause of pharyngitis and skin infections in children. It is also the causative agent of dangerous immune-complications such as rheumatic fever and rheumatic heart disease which are common in Yemen. The aim of this study was to determine the throat carriage rate of Streptococcus pyogenes among asymptomatic school children in Sana'a city. RESULTS: A cross-sectional study was conducted from December to March of years 2012-2016. A total of 813 asymptomatic school children whose antistreptolysin O test was negative were included. The mean age of the students was 10.5 ± 2.8 years with a range from 5 to 15 years old. Throat swab and blood sample were taking from each student. One hundred and four (12.8%) healthy students were found to be Streptococcus pyogenes carriers. Pharyngeal Streptococcus pyogenes carriage rate was statistically insignificant among different age groups. However, it was found to be more common among females (66, 15%) than males (38, 10%) with statistically significant difference (χ2 = 4.52, P = 0.04). This study showed a high asymptomatic carriage rate of Streptococcus pyogenes in the throat of healthy school children in Sana'a city, Yemen.

Impact of Metabolic Syndrome Factors on Testosterone and SHBG in Type 2 Diabetes Mellitus and Metabolic Syndrome.

OBJECTIVE: Several studies have often reported low testosterone and SHBG to be associated with type 2 DM and the metabolic syndrome (MetS). Our objective was to determine the impact of metabolic syndrome and diabetic parameters on testosterone and SHBG in both MetS subjects and type 2 DM patients. METHODS: In this study, 120 Yemeni male aged 30-70 years old were enrolled, 30 of whom were healthy subjects with BMI < 25 kg/m2 that served as control, 30 MetS, 30 type 2 DM without MetS, and 30 type 2 DM with MetS according to IDF criteria. RESULTS: Testosterone (free and total) and SHBG were significantly lower in MetS subjects and modestly reduced in type 2 DM with and without MetS. Stepwise linear regression showed free and total testosterone to be negatively affected by waist circumference, and univariate analysis shows this significant difference to disappear when adjusted for waist circumference. On the other hand, stepwise linear regression showed SHBG to be positively affected by testosterone and age and negatively affected by FBG and TG. Univariate analysis shows this observed significant difference to disappear when adjusted for testosterone. CONCLUSION: Abdominal obesity is a major determinant of low testosterone levels irrespective of diabetes status. Thus, supporting evidence suggesting that the causative relationship between the often low testosterone and type 2 DM might be bidirectional or even multidirectional and interrelated with obesity, MetS, and IR.

Anger, anxiety, and depressive affect as predictors of stress-induced cortisol production in khat and tobacco users.

INTRODUCTION: Glucocorticoid activity is disrupted in substance users including khat chewers who also use tobacco. Anger, dysphoria, and anxiety can mediate this relationship. The aim of this study was to contrast emotion dysregulation and substance use variables as predictors of post-stress cortisol output. MATERIALS AND METHODS: Comparable numbers of males (n = 90) and females (n = 85) including controls, khat only, and concurrent khat and tobacco users participated in a stress study. Depressive affect, anxiety, anger, substance use patterns, and saliva samples were collected following a standardized laboratory stress manipulation. RESULTS: Regression analysis showed that high depression and low anxiety was associated with high post-stress cortisol, but only in co-users of tobacco and khat. Males, but not females, showed a significant association between co-use of khat and tobacco and cortisol, which appears to be mediated by frequency of use. The link between anxiety and post-stress cortisol in the co-users remained significant after controlling for nicotine dependence and substance use frequency. CONCLUSION: Anxiety predicted the neuroendocrine consequences of concurrent use of tobacco and khat above and beyond sex, nicotine dependence, anger, and substance use frequency. Sex differences, however, are related to differences in nicotine dependence.

Contributions of IKZF1, DDC, CDKN2A, CEBPE, and LMO1 Gene Polymorphisms to Acute Lymphoblastic Leukemia in a Yemeni Population.

BACKGROUND: Genome-wide and candidate gene association studies have previously revealed links between a predisposition to acute lymphoblastic leukemia (ALL) and genetic polymorphisms in the following genes: IKZF1 (7p12.2; ID: 10320), DDC (7p12.2; ID: 1644), CDKN2A (9p21.3; ID: 1029), CEBPE (14q11.2; ID: 1053), and LMO1 (11p15; ID: 4004). In this study, we aimed to conduct an investigation into the possible association between polymorphisms in these genes and ALL within a sample of Yemeni children of Arab-Asian descent. METHODS: Seven single-nucleotide polymorphisms (SNPs) in IKZF1, three SNPs in DDC, two SNPs in CDKN2A, two SNPs in CEBPE, and three SNPs in LMO1 were genotyped in 289 Yemeni children (136 cases and 153 controls), using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Logistic regression analyses were used to estimate ALL risk, and the strength of association was expressed as odds ratios with 95% confidence intervals. RESULTS: We found that the IKZF1 SNP rs10235796 C allele (p = 0.002), the IKZF1 rs6964969 A>G polymorphism (p = 0.048, GG vs. AA), the CDKN2A rs3731246 G>C polymorphism (p = 0.047, GC+CC vs. GG), and the CDKN2A SNP rs3731246 C allele (p = 0.007) were significantly associated with ALL in Yemenis of Arab-Asian descent. In addition, a borderline association was found between IKZF1 rs4132601 T>G variant and ALL risk. No associations were found between the IKZF1 SNPs (rs11978267; rs7789635), DDC SNPs (rs3779084; rs880028; rs7809758), CDKN2A SNP (rs3731217), the CEBPE SNPs (rs2239633; rs12434881) and LMO1 SNPs (rs442264; rs3794012; rs4237770) with ALL in Yemeni children. CONCLUSION: The IKZF1 SNPs, rs10235796 and rs6964969, and the CDKN2A SNP rs3731246 (previously unreported) could serve as risk markers for ALL susceptibility in Yemeni children.

Association of ARID5B gene variants with acute lymphoblastic leukemia in Yemeni children.

Studies have shown an association between ARID5B gene polymorphisms and childhood acute lymphoblastic leukemia. However, the association between ARID5B variants and acute lymphoblastic leukemia among the Arab population still needs to be studied. The aim of this study was to investigate the association between ARID5B variants with acute lymphoblastic leukemia in Yemeni children. A total of 14 ARID5B gene single nucleotide polymorphisms (SNPs) were genotyped in 289 Yemeni children, of whom 136 had acute lymphoblastic leukemia and 153 were controls, using the nanofluidic Dynamic Array (Fluidigm 192.24 Dynamic Array). Using logistic regression adjusted for age and gender, the risks of acute lymphoblastic leukemia were presented as odds ratios and 95% confidence intervals. We found that nine SNPs were associated with acute lymphoblastic leukemia under additive genetic models: rs7073837, rs10740055, rs7089424, rs10821936, rs4506592, rs10994982, rs7896246, rs10821938, and rs7923074. Furthermore, the recessive models revealed that six SNPs were risk factors for acute lymphoblastic leukemia: rs10740055, rs7089424, rs10994982, rs7896246, rs10821938, and rs7923074. The gender-specific impact of these SNPs under the recessive genetic model revealed that SNPs rs10740055, rs10994982, and rs6479779 in females, and rs10821938 and rs7923074 in males were significantly associated with acute lymphoblastic leukemia risk. Under the dominant model, SNPs rs7073837, rs10821936, rs7896246, and rs6479778 in males only showed striking association with acute lymphoblastic leukemia. The additive model revealed that SNPs with significant association with acute lymphoblastic leukemia were rs10821936 (both males and females); rs7073837, rs10740055, rs10994982, and rs4948487 (females only); and rs7089424, rs7896246, rs10821938, and rs7923074 (males only). In addition, the ARID5B haplotype block (CGAACACAA) showed a higher risk for acute lymphoblastic leukemia. The haplotype (CCCGACTGC) was associated with protection against acute lymphoblastic leukemia. In conclusion, our study has shown that ARID5B variants are associated with acute lymphoblastic leukemia in Yemeni children with several gender biases of ARID5B single nucleotide polymorphisms reported.

Chad Genetic Diversity Reveals an African History Marked by Multiple Holocene Eurasian Migrations.

Understanding human genetic diversity in Africa is important for interpreting the evolution of all humans, yet vast regions in Africa, such as Chad, remain genetically poorly investigated. Here, we use genotype data from 480 samples from Chad, the Near East, and southern Europe, as well as whole-genome sequencing from 19 of them, to show that many populations today derive their genomes from ancient African-Eurasian admixtures. We found evidence of early Eurasian backflow to Africa in people speaking the unclassified isolate Laal language in southern Chad and estimate from linkage-disequilibrium decay that this occurred 4,750-7,200 years ago. It brought to Africa a Y chromosome lineage (R1b-V88) whose closest relatives are widespread in present-day Eurasia; we estimate from sequence data that the Chad R1b-V88 Y chromosomes coalesced 5,700-7,300 years ago. This migration could thus have originated among Near Eastern farmers during the African Humid Period. We also found that the previously documented Eurasian backflow into Africa, which occurred ∼3,000 years ago and was thought to be mostly limited to East Africa, had a more westward impact affecting populations in northern Chad, such as the Toubou, who have 20%-30% Eurasian ancestry today. We observed a decline in heterozygosity in admixed Africans and found that the Eurasian admixture can bias inferences on their coalescent history and confound genetic signals from adaptation and archaic introgression.

Association of adipokines, leptin/adiponectin ratio and C-reactive protein with obesity and type 2 diabetes mellitus.

OBJECTIVE: Alterations in plasma adipokines and/or inflammatory parameters in Type 2 DM remain vague as to whether they are due to obesity and/or directly associated with the diabetic state. Our objective was to compare plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and hs-CRP in obese non-diabetic subjects and non-obese Type 2 DM patients, as well as determining the association of these adipokines with MetS and diabetes-related quantitative traits. METHODS: In this study, 92 Yemeni male volunteers aged 25-60 years old were enrolled, 31 of whom were healthy subjects with BMI < 25 kg/m(2) served as control; 30 non-diabetic obese subjects BMI ≥ 30 kg/m(2) and FBG < 6.1 mmol/l; and 31 non-obese Type 2 DM with FBG > 7 mmol/l and BMI < 25 kg/m(2). RESULTS: Adiponectin was lower in obese subjects, with no differences between non-obese Type 2 DM patients and controls. In contrast, leptin, LAR and hs-CRP were higher in both obese subjects and non-obese Type 2 DM patients. Linear regression analysis showed adiponectin to be associated negatively with BMI, waist circumference, insulin, HOMA-ß and HOMA-IR; whereas leptin, LAR and hs-CRP were associated positively with BMI, waist circumference, TG, FBG, insulin, HOMA-ß and HOMA-IR. Moreover, adiponectin negatively correlated with leptin, LAR and hs-CRP; whereas leptin and LAR positively correlated with hs-CRP and with each other. CONCLUSION: Plasma adiponectin is not affected by diabetes per se, suggesting that its alterations in Type 2 DM may be due to obesity and may be an important link between adiposity, IR and Type 2 DM.

The prospect of malaria elimination in the Arabian Peninsula: a population genetic approach.

BACKGROUND: In the Arabian Peninsula malaria control is progressing steadily, backed by adequate logistic and political support. As a result, transmission has been interrupted throughout the region, with exception of limited sites in Yemen and Saudi Arabia. Here we examined Plasmodium falciparum parasites in these sites to assess if the above success has limited diversity and gene flow. METHODS: We examined 108 P. falciparum isolates in three sites in Yemen (Taiz, Dhamar and Hodeidah) and 91 isolates from Saudi Arabia (Jazan). Nine microsatellites were analyzed for allelic diversity, multi-locus haplotype and inter-population differentiation. RESULTS: Diversity at each locus (unbiased heterozygosity [H]) was relatively lower in Yemen; (Hodeidah, H=0.615, Taiz, H=0.66, Dhamar, H=0.481), compared to Saudi Arabia (Jazan, H=0.76). Microsatellites were distributed widely and private alleles, detected in a single population, were rare. Pairwise comparisons revealed that parasites population in Dhamar was relatively distanced (FST=0.19). However, Taiz (Yemen) (FST=0.065) and Hodeidah (FST=0.107) populations were closer to that in Jazan (Saudi Arabia). Nonetheless, parasites in the four sites can be considered as one population. CONCLUSION: Although malaria risk in Saudi Arabia has been cut considerably, the extent of diversity and parasite genetic structure are indicative of a large population size. Elimination strategy should target demographic factors that favor parasite dispersal and flow of imported malaria.

Evaluation of chemopreventive effects of Acanthus ilicifolius against azoxymethane-induced aberrant Crypt Foci in the rat colon.

BACKGROUND: Acanthus ilicifolius, a mangrove medicinal plant, is traditionally used to treat a variety of diseases. The aim of this research is to assess the chemoprotective outcomes of A. ilicifolius ethanolic extract against azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) in rats. METHODOLOGY/PRINCIPAL FINDINGS: In our study, rats were arranged in to five groups. Rats in the normal control group were given subcutaneous injections of normal saline once weekly for 2 weeks. The AOM control, reference and treatment groups were given subcutaneous injection of AOM, 15 mg/kg body weight, once weekly for 2 weeks each. The reference group was treated with 35 mg/kg 5-Fluorouracil via intraperitoneal injection once weekly for 8 weeks, and the treatment groups were administered by gavage with 250 and 500 mg/kg A. ilicifolius extract daily for 8 weeks. Both normal and AOM control groups received the vehicle; 10% Tween-20 only. Rats treated with 250 mg/kg and 500 mg/kg of A. ilicifolius extracts showed a decrease in the mean number of ACF by 65% and 53%, respectively. Those fed with A. ilicifolius showed significantly decreased multiplicity of ACF formations when compared with the results from the AOM control group. The 250 mg/kg A. ilicifolius treatment group showed significant decreases in lipid peroxidation MDA levels when compared with the AOM control group. In immunohistochemistry staining, the proliferating nuclear cell antigen (PCNA)-positive cells were significantly higher in the AOM control group than in the A. ilicifolius-treated groups. RT-PCR showed that A. ilicifolius caused a change in the regulation of apoptosis-related genes expression. CONCLUSION/SIGNIFICANCE: The results of the current study show that AOM-treated rats receiving oral exposure to A. ilicifolius demonstrated a significant decrease in the number of ACF in the colon when compared to AOM-treated rats receiving vehicle only. A ilicifolius may be an effective herbal approach for the prevention of AOM-induced ACF in the rat colon.

Comparison of adults with insulin resistance (IR) in latent autoimmune diabetes versus IR in glutamic acid decarboxylase antibody-negative diabetes.

INTRODUCTION: Insulin resistance in latent autoimmune diabetes in adults (LADA) patients is controversial. The aim of this study was to evaluate insulin resistance and its related factors (metabolic syndrome parameters) among subjects with LADA and glutamic acid decarboxylase antibodies (GADA) negative diabetes, as well as the impact of these factors on insulin resistance. MATERIALS AND METHODS: GADA levels were investigated in 1140 diabetic patients aged between 30 and 70 years. Insulin resistance and metabolic syndrome parameters were assessed in LADA and GAD-negative diabetic patients by general linear model. In addition, the impact of metabolic syndrome factors on insulin resistance was assessed in LADA and glutamic acid decarboxylase (GAD)-negative diabetic patients. RESULTS: LADA was diagnosed in 33 subjects from 1140 Malaysian diabetic patients (prevalence = 2.9%). The results showed that LADA patients had higher insulin resistance and high density lipoprotein cholesterol (HDLc) (P = 0.003 and 0.00017 respectively) and lower body mass index (BMI) (P = 0.007) compared to GAD-negative diabetic patients. The HDLc was associated with decreased insulin resistance in LADA patients (P = 0.041), whereas HbA1c, triacylglycerides (TG) and waist were associated with increased insulin resistance in GAD-negative diabetic patients (P = 3.6×10⁻¹², 1.01×10⁻5 and 0.004 respectively). HbA1c was highly associated with decreasing ß-cell function in both LADA (P = 0.009) and GAD-negative diabetic subjects (P = 2.2×10⁻²8). CONCLUSION: Insulin resistance is significantly higher in LADA than GAD-negative diabetic Malaysian subjects.

Contribution of SLC30A8 variants to the risk of type 2 diabetes in a multi-ethnic population: a case control study.

BACKGROUND: Several studies have shown the association of solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 with type 2 diabetes (T2D). However, the association of alternative variants and haplotypes of SLC30A8 with T2D have not been studied in different populations. The aim of this study is to assess the association of the alternative SLC30A8 variants, rs7002176 and rs1995222 as well as the most common variant, rs13266634 and haplotypes with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian subjects. METHODS: Single nucleotide polymorphisms (SNPs) of SLC30A8; rs7002176, rs1995222 and rs13266634 were genotyped in 1140 T2D and 973 non-diabetic control subjects. Of these, 33 GADA positive diabetic subjects and 353 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. RESULTS: The recessive genetic model controlled for age, race, gender and BMI shows that the alternative SLC30A8 variant, rs1995222 is associated with GADA negative diabetes (OR = 1.29, P = 0.02) in Malaysian subjects. The most common variant, rs13266634 is also associated with GADA negative diabetes (OR = 1.45, P = 0.001). This association is more pronounced among Malaysian Indians (OR = 1.93, P = 0.001). Moreover, the CG haplotype and CG-CG diplotype have been equally associated with increased diabetic risk (OR = 1.67, P = 8.6 × 10-5). CONCLUSIONS: SLC30A8 SNPs and haplotypes are associated with GADA negative diabetes in Malaysian subjects, and this association is markedly higher among Malaysian Indian subjects.

Catha Edulis (Khat) Chewing Decreases Serum Levels of Iron, Ferritin and Vitamin B12 and Increases Folic Acid.

BACKGROUND: Catha edulis (Khat) is customarily chewed to attain a state of stimulation and reduce physical fatigue. In view of the reported common adverse effects of Khat, the aim of this study was to evaluate the levels of iron, ferritin, folic acid, vitamin B(12) and body mass index (BMI) as nutritive indicators in Yemeni Khat chewers. METHODS: This study was a prospective cohort study, carried out on 90 male workers aged 19 - 23 years old; 45 were healthy non-Khat chewers serving as control group and 45 were regular Khat chewers. Serum iron, ferritin, folic acid, vitamin B(12) and body mass index were measured at baseline and after a year of follow up. RESULTS: Serum iron and BMI were significantly (p < 0.01) lower at baseline in Khat chewers by 9 % and 6 %, respectively; whereas ferritin, folic acid and vitamin B(12) were non-significantly different from non-Khat chewers. In the follow-up one year later, serum iron, ferritin, vitamin B(12) and BMI were significantly (p < 0.001) lower in Khat chewers by 19.0, 31.4, 20.6 and 10.7 %; whereas folic acid was significantly (p = 0.007) higher by 26.7 %. Comparison within groups showed serum iron, ferritin, and BMI to be significantly (p < 0.01) decreased after one year in the Khat chewers with respect to its baseline; whereas folic acid significantly (p < 0.001) increased. CONCLUSION: This study shows Khat chewers to be more susceptible to malnutrition, which should be considered by the general population and the public health authorities.

Factors affecting dengue fever knowledge, attitudes and practices among selected urban, semi-urban and rural communities in Malaysia.

Dengue fever is a major public health problem in Malaysia. This study aimed to assess factors affecting knowledge, attitudes, and practices regarding dengue fever among a selected population in Malaysia. A descriptive, community-based, cross sectional study was conducted with 300 participants from three different geographical settings in urban, semi-urban, and rural areas within the states of Selangor and Kuala Lumpur. The questionnaire included questions on demographic data, knowledge, attitudes, and practices regarding dengue fever. Mean age of respondents was 34.4 (+/- 5.7) years, and the age ranged from 18 to 65 years. The majority of respondents were married (54.7%), Malays (72.7%) and heard about dengue fever (89.7%). Television was the common source of information about dengue fever (97.0%). Participants answered 4 out of 15 items of knowledge incorrectly. There was no significant association between knowledge score and socio-demographic factors. About one-fifth of the respondents (24%) believed that immediate treatment is not necessary for dengue fever, and the majority of them were not afraid of the disease (96.0%). Attitudes toward dengue fever were significantly associated with the level of education and employment status (p < 0.05). Practice was associated significantly with age, marital status, and geographic area (p < 0.05) and knowledge on dengue fever (p = 0.030). There is a need to increase health promotion activities through campaigns and social mobilization to increase knowledge regarding dengue fever. This would help to mold positive attitudes and cultivate better preventive practices among the public to eliminate dengue in the country.

IGF2BP2 alternative variants associated with glutamic acid decarboxylase antibodies negative diabetes in Malaysian subjects.

BACKGROUND: The association of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) common variants (rs4402960 and rs1470579) with type 2 diabetes (T2D) has been performed in different populations. The aim of this study was to evaluate the association of alternative variants of IGF2BP2; rs6777038, rs16860234 and rs7651090 with glutamic acid decarboxylase antibodies (GADA) negative diabetes in Malaysian Subjects. METHODS/PRINCIPAL FINDINGS: IGF2BP2; rs6777038, rs16860234 and rs7651090 single nucleotide polymorphisms (SNPs) were genotyped in 1107 GADA negative diabetic patients and 620 control subjects of Asian from Malaysia. The additive genetic model adjusted for age, race, gender and BMI showed that alternative variants; rs6777038, rs16860234 and rs7651090 of IGF2BP2 associated with GADA negative diabetes (OR = 1.21; 1.36; 1.35, P = 0.03; 0.0004; 0.0002, respectively). In addition, the CCG haplotype and diplotype CCG-TCG increased the risk of diabetes (OR = 1.51, P = 0.01; OR = 2.36, P = 0.009, respectively). CONCLUSIONS/SIGNIFICANCE: IGF2BP2 alternative variants were associated with GADA negative diabetes. The IGF2BP2 haplotypes and diplotypes increased the risk of diabetes in Malaysian subject.