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.
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.
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.
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.
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.
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.
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.
The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM.
Insertion/deletion (
I/D
) polymorphism, of a 287-bp
Alu
repetitive sequence in intron 16 of the angiotensin-converting enzyme (ACE) gene has been shown to be associated with different types of ...diseases and has been widely investigated in different populations with different ethnic origins. Various reports were published suggesting inter-ethnic variations in the frequency of allelic forms of the ACE gene. The goal of this study was to test the distribution of alleles and the different genotypes of ACE (
I
/
D
) polymorphism in Bahraini subjects and compare the results with those obtained from other population studies. The Bahraini population is an Arabic peninsula population with a high prevalence of T2DM and hypertension. A total of 560 unrelated Bahraini individuals were recruited in this study and the presence (insertion)/absence (deletion) (
I/D
) polymorphism of a 287-bp Alu1 element inside intron 16 of the ACE gene was done by PCR-based assays and the presence or absence of the genotypes were analyzed by the gel electrophoresis. The distribution of
II
,
ID
, and
DD
genotypes showed differences among Bahraini subjects, and the frequency of the
D
allele was significantly (
P
< 0.05) higher in the studied group. The results obtained for the
D
allele are consistent with those obtained from previous studies among Arabs, Africans, and Caucasians, but differs significantly (
P
< 0.05) from those in Japanese and Chinese, thus proving the ethnic variation in the distribution of the ACE alleles in different populations.
Context: Preeclampsia is a severe complication of human pregnancy often associated with maternal risk factors. Insulin resistance represents a major risk for developing preeclampsia during pregnancy.
...Objective: A putative second messenger of insulin, inositol phosphoglycan P type (P-IPG), was previously shown to be highly increased during active preeclampsia. Its association with insulin resistance was investigated.
Design and Setting: A cross-sectional study was carried out in a referral center.
Patients: Nine preeclamptic (PE) and 18 healthy women were recruited and matched for maternal age, body mass index, parity, and ethnicity in a 1:2 ratio. Placental specimens were collected immediately after delivery.
Intervention: Placental tissue was incubated with insulin and P-IPG production assessed. Insulin signaling proteins were subsequently studied by immunoblotting.
Results: P-IPG extracted from human term placentas upon incubation with insulin was found to be far lower in those with preeclampsia than controls (P < 0.001). Immunoblotting studies revealed serine phosphorylation of insulin receptor substrate-1 and -2 in PE placentas (P < 0.001) with downstream impairment of insulin signaling. The activation of the p85 regulatory subunit of phosphatidylinositol 3- kinase was markedly decreased in PE samples (P < 0.001).
Conclusions: These findings highlight the importance of P-IPG in active preeclampsia and demonstrate a substantially different response to the insulin stimulus of human PE placentas. Acquired alterations in activation of proteins involved in insulin signaling may play a role in the complex pathogenesis of preeclampsia, probably as a consequence of the immunological dysfunction that occurs in this syndrome. These results seem to confirm an insulin-resistant state in PE placenta and shed a different light on its role in the pathogenesis of this disease with potential therapeutic implications.
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.
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.
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.
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.
Introduction:
Bahrain has a high prevalence of type 2 diabetes mellitus (T2DM). Previously, Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism was found to be associated with ...T2DM in Bahrainis. The relationship between the disease progression in Bahraini T2DM population and the genetic polymorphism of methylene-tetrahydrofolate-reductase (MTHFR) C677T is still under investigation.
Aim:
The current study investigated the distribution of MTHFR C677T gene polymorphism among Bahraini T2DM patients and examined the interaction between ACE I/D and MTHFR C677T polymorphisms on the risk of developing T2DM and its long-term complications.
Materials and methods:
Polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP) were used to test for the presence of ACE I/D and MTHFR C677T polymorphisms in 171 patients with T2DM compared to 188 healthy (non-diabetic) age-matched control subjects from Bahrain.
Results:
The incidence of the DD genotype and D allele of the ACE gene was high among Bahraini T2DM patients. MTHFR allele and genotype frequencies did not differ between patients and controls. No significant relationship was identified between the combinations of ACE I/D and MTHFR C677T polymorphisms with T2DM.
Conclusions:
The results clearly showed an association of the ACE I/D polymorphism with the progression of T2DM, but when it interacts with MTHFR polymorphism no influence was detected on the increased risk of T2DM.
Bahrain has one of the highest incidence rates of type 2 diabetes mellitus (T2DM). Development of diabetic nephropathy (DN) as a complication was noticed in some patients while absent in others. This ...interesting observation raises the role of certain genetic risk factors for the development of DN. Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism was found to be associated with T2DM. While some patients have predisposition to DN in the population, others have negative association. The present case-control association study was designed to investigate the association of ACE I/D polymorphism in T2DM patients in Bahrain especially in those who developed DN. A total of 360 T2DM patients (110 with DN and 250 without DN) and 360 healthy (non-diabetic) age-matched subjects were recruited for this study for comparison. The presence (insertion)/absence (deletion) (I/D) polymorphism of a 287-bp Alu1 element inside intron 16 of the ACE gene was investigated using PCR-gel electrophoresis. The results show that the distribution of the homozygote DD genotype of the ACE gene was high among Bahraini T2DM patients compared to the healthy non-diabetic subjects. In addition, the distribution of the deletion (D) allele was high among Bahraini T2DM patients with DN when compared to the healthy non-diabetic subjects. However, there was no significant difference in the distribution of ACE I/D allele and genotypes between DN patients when compared to those T2DM patients without DN. The results obtained in this study are in closely agreement with some previous reports which show a strong association of ACE polymorphism with T2DM patients, yet not a risk factor for development of DN.
Abnormal secretion of P-type inositol phosphoglycans (IPG-P) has been described in maternal urine of pre-eclamptic women. The aim of this study was to determine the origin of production of IPG-P. We ...examined the IPG-P content of maternal and fetal serum, maternal urine and amniotic fluid in both normal pregnancy and pre-eclampsia.
Established extraction and bioactivity assay techniques were used to compare total IPG-P levels in serum samples, and a polyclonal-antibody-based ELISA to assay the amniotic fluid and urine samples in matched pairs of women.
Eleven women with pre-eclampsia requiring caesarean section (subjects), 11 pregnant women requiring elective caesarean section for reasons other than pre-eclampsia (controls).
Our data confirm the abnormal level of IPG-P in maternal urine during pre-eclampsia. Moreover, IPG-P levels were higher in umbilical sera than in maternal sera samples. Amniotic fluid as well as urine ELISA results were significantly higher in the pre-eclamptic group compared with normal controls. Total IPG-P bioactivity in serum did not vary between serum compartments in normal pregnancy. Uterine vein IPG-P levels were lower in pre-eclampsia when compared with normal pregnancy. A possible correlation was observed between urine and amniotic fluid levels in normal women. No correlation was observed between measured blood levels and those in urine and amniotic fluid.
It is hypothesized that steady state equilibrium of IPG-P in serum in normal pregnancy is disrupted in pre-eclampsia. Additionally, an abnormal IPG-P sub-fraction, detectable in urine and amniotic fluid, may be present and involved in the pathophysiology of the syndrome, although sites of production of this abnormal form remain unclear.
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.
Clinical and experimental studies have reported the role of homocysteine in ventricular hypertrophy. Activation of the renin-angiotensin system mediated by angiotensin II type 1 (AT1) receptor has ...also been suggested to contribute to the pathogenesis of ventricular hypertrophy. There are also reports suggesting the affect of angiotensin II (Ang II) on cardiac hypertrophy is mediated by hyperhomocysteinemia. However, there is limited information on the mechanisms of the possible relationship between homocysteine and Ang II in ventricular hypertrophy. In this study we tested the hypothesis that hyperhomocysteinemia induced ventricular hypertrophy and remodelling may be mediated through activation of Ang II AT1-receptors in rats.
This study was conducted on control non-treated rats (n=13), methionine-treated rats (1.5 mg/kg/day, n=18) and methionine plus oral AT1 antagonist (valsartan, 30 mg/kg/day, n=13) treated rats for 56 days. Systolic blood pressure (SBP) was determined in rats at baseline, 28 and 56 days. Echocardiography was also performed in all rats after eight weeks, and blood samples were obtained for determination of plasma tHcy. Rats were then sacrificed for histopathological and biochemical assessment of cardiac structure.
The SBP in the methionine-treated rats was significantly higher compared with controls and significantly lower compared with the methionine-valsartan group at 28 and 56 days (p<0.001). In addition, left ventricular wall thickness (LVWT) in the methionine-valsartan group (4.36+0.11 mm) was significantly lower compared with the methionine group (5.0+0.23 mm, p=0.03). Furthermore, cardiac collagen to total protein ratio was significantly lower in the methionine-valsartan group (2.19+0.11%) compared with the methionine group (2.64+0.08%, p=0.026). Fractional shortening (FS) was not significantly different between groups.
Results from this study suggest that hyperhomocysteinemia-induced hypertension and ventricular hypertrophy in rats are mediated, at least partly; by Ang II activation of AT1-receptors.
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