Gender-Dependent Association of Vitamin D Deficiency with Obesity and Hypercholesterolemia (LDLC) in Adults.

BACKGROUND: Obesity, dyslipidemia and vitamin D deficiency are growing health problems in the Arabian Gulf region. Their association with each other is yet to be clarified. METHODS: Three-hundred and fourteen Bahraini adults, 164 males and 150 females comparable in median age (34.5 vs. 31.0 yrs), body mass index (BMI), and ethnicity were recruited. The plasma level of 25-hydroxyvitamin D3 (25OHD3) was measured by chemiluminescent immunoassay and lipid profile parameters were measured by an automated clinical chemistry analyzer. Based on BMI, study subjects were grouped into underweight, normal, overweight, moderate obesity, and severe obesity subjects. RESULTS: The results revealed an extremely high prevalence of vitamin D deficiency (79.9%) and insufficiency (18.8%). The predictors of low 25OHD3 levels were female gender, small age, conservative dressing, least exposure to sunlight, and less fish intake. In all subjects, the lowest 25OHD3 level was seen in underweight and severe obesity groups. Furthermore, the 25OHD3 level was significantly higher in males as compared to females and it was positively correlated with the age. However, detailed analysis showed that overweight males unlike females had the highest 25OHD3 levels which were significantly higher than in the severely obese males. While the lipid profile parameters were positively correlated with BMI, the total and LDL cholesterols were negatively correlated with the levels of 25OHD3 in males. CONCLUSION: Vitamin D deficiency was associated with both severely obese and underweight subjects, in the former it was likely to be institutional while in the latter it was likely to be nutritional. Furthermore, hypercholesterolemia (LDL-C) was associated with 25OHD3 sub-normality. Further analysis revealed that the significant associations were gender-dependent.

Leu72Met and Other Intronic Polymorphisms in the GHRL and GHSR Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population.

BACKGROUND: Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associations raise the issue of 'which SNPs in which populations.' The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis. METHODS: Blood was collected from 208 Saudi subjects with (n=107) and without (n=101) T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT) and GHSR (rs509030 GC) genes. In addition, plasma GHRL levels were measured by a radioimmunoassay. RESULTS: None of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region. CONCLUSION: Neither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR.

Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects.

BACKGROUND: Although the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM. METHODS: Patients with T2DM (n=107, cases) and non-diabetic apparently healthy subjects (n=101, controls) from Saudi Arabia were included in this study. The biochemical profiles and plasma insulin levels of all subjects were analyzed, and IR was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Active ghrelin levels in plasma were measured using the radioimmunoassay technique. RESULTS: Only 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3 ≤HOMA-IR <5). HOMA-IR values were not associated with age, disease duration, or gender. Importantly, T2DM itself and the co-occurrence of IR with T2DM were significantly associated with low plasma ghrelin levels. However, ghrelin levels were inversely correlated with the HOMA-IR index, body weight, and fasting plasma insulin levels, mainly in the control subjects, which was indicative of the breakdown of metabolic homeostasis in T2DM. CONCLUSION: The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM.

Independent associations of polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes with obesity and plasma 25OHD3 levels demonstrate sex dimorphism.

We investigated a possible association between polymorphisms in vitamin D binding protein (GC) and vitamin D receptor (VDR) genes and obesity in Bahraini adults. For this purpose, 406 subjects with varying body mass indexes (BMIs) were selected. Plasma levels of 25-hydroxyvitamin D3 (25OHD3) were measured by chemiluminescence immunoassay. Six single nucleotide polymorphisms, 2 in the VDR gene (rs731236 TC and rs12721377 AG) and 4 in the GC gene (rs2282679 AC, rs4588 CA, rs7041 GT, and rs2298849 TC), were genotyped by real-time polymerase chain reaction. We found that the rs7041 minor allele (G) and rare genotype (GG) were associated with higher BMI (p = 0.007 and p = 0.012, respectively), but they did not influence 25OHD3 levels. However, the minor alleles of rs2282679 (A) and rs4588 (C) were associated with low 25OHD3 plasma levels (p = 0.039 and p = 0.021, respectively), but not with BMI. Having categorized the subjects based on their sex, we found that (i) rs7041 GG associated with high BMI in females (p = 0.003), (ii) rs4588 CC associated with high BMI in females (p = 0.034) and low 25OHD3 levels in males (p = 0.009), and (iii) rs12721377 AA associated with low 25OHD3 levels in females (p = 0.039). Notably, none of the common haplotypes (6 in the GC gene and 3 in the VDR gene) were associated with BMI. Therefore, polymorphisms in the GC (rs2282679, rs4588, rs7041) and VDR (rs12721377) genes were independently associated with obesity and 25OHD3 levels with a clear sex dimorphism.

Leptin-to-adiponectin, adiponectin-to-leptin ratios, and insulin are specific and sensitive markers associated with polycystic ovary syndrome: a case-control study from Bahrain.

OBJECTIVE: Hyperinsulinemia and adipokines such as leptin and adiponectin with respective proatherogenic and antiatherogenic properties are reported to be the major contributors to pathogenesis of polycystic ovary syndrome (PCOS), including to the development of type 2 diabetes and coronary artery disease. In this study, the association of hyperinsulinemia, hyperleptinemia, hypoadiponectinemia, high leptin-to-adiponectin (L/A) and adiponectin-to-leptin (A/L) ratios as risk factors associated with PCOS in Bahraini women was investigated. PARTICIPANTS AND METHODS: Serum levels of insulin, leptin, adiponectin, cholesterol, triglyceride, A/L and L/A ratios were compared in women with PCOS and controls to investigate tentative and potential diagnostic markers for women with PCOS. RESULTS: Insulin was significantly higher in PCOS cases than controls (15.0±3.0 vs. 6.5±1.72, P<0.001). Leptin was significantly higher in PCOS cases than in controls (39.9±4.6 vs. 26.4±3.4, P<0.001), whereas adiponectin was significantly lower in PCOS cases than in controls (8.7±3.0 vs. 11.1±3.6, P<0.001). In addition, L/A ratios were significantly higher in PCOS cases than in controls (4.8±2.7 vs. 2.3±1.6, P<0.001), whereas A/L ratios were significantly lower in PCOS cases than in controls (0.25±0.08 vs. 0.50±0.1, P<0.001). In multivariate logistic regression analyses, insulin [odds ratio (OR)=2.1, confidence interval (CI) 1.2-3.8, P=0.01], A/L (OR=1.6, CI 1.4-7.2, P=0.03), and L/A (OR=1.4, CI 1.2-2.0, P=0.04) were independently associated with PCOS. Receiver operating characteristic analyses showed that the best predictive markers for PCOS were insulin [area under the curve (AUC)=0.937, CI 0.887-0.989] L/A and A/L ratios (AUC=0.861, CI 0.786-0.936), indicating their high sensitivity and specificity for diagnosis of PCOS. CONCLUSION: In Bahraini women with PCOS, insulin, L/A, and A/L ratios seem to be the best markers to distinguish women with and without PCOS.

Cardiovascular Responses to Tonic Pain in REM Sleep-Deprived Rats: Role of Melatonin and Beta Endorphin.

OBJECTIVE: Chronic pain is associated with increased incidence of hypertension. Sleep deprivation, common in patients with chronic pain, is associated with increased blood pressure and heart rate. This study was designed to determine whether sleep deprivation induces increased cardiovascular responses to pain. In addition; we examined the role of melatonin and endorphins in mediating these responses. METHOD: The study was conducted in Sprague-Dawely rats divided into a control group (n=8) and Rapid Eye Moment sleep deprived (REMSD) group (n=8). REM sleep deprivation was done for three days using the inverted flowerpot technique. Systolic BP and HR were recorded at baseline as well as 5, 10 and 30 minutes after intra-plantar formalin injection. In addition, serum melatonin and endorphin levels were determined. RESULTS: Under basal conditions, BP and HR and following acute pain (1(st) phase of formalin injection) were comparable with non-sleep deprived (non-SD) state. In contrast, the REMSD rats showed significantly greater increases in HR and BP during the 2(nd) phase of formalin pain as compared to non-SD state. These changes were associated with significant reductions in serum melatonin and endorphin levels in REMSD rats. CONCLUSION: These data indicate that exaggerated blood pressure and HR responsiveness to pain in sleep deprivation could be mediated through reductions in melatonin and endorphin.

The Middle-East connection of Wolman Disease.

The clinical, laboratory and cytological features of 2 Bahraini infants with Wolman's disease are described. While one of the cases showed the classical diagnostic features, the other case exhibited a few atypical features such as lack of adrenal calcification and unusual morphology of vacuolated marrow macrophages. Literature review shows that this disorder may not be rare in this region.