Leptin and the rs2167270 Polymorphism Are Associated with Glycemic Control in Type Two Diabetes Mellitus Patients on Metformin Therapy.

Background and Objectives: Type two diabetes mellitus (T2DM) is a chronic disease with debilitating complications and high mortality. Evidence indicates that good glycemic control delays disease progression and is hence a target of disease management protocols. Nonetheless, some patients cannot maintain glycemic control. This study aimed to investigate the association between serum leptin levels and several SNPs of the LEP gene with the lack of glycemic control in T2DM patients on metformin therapy. Materials and Methods: In a hospital-based case-control study, 170 patients with poor glycemic control and 170 patients with good glycemic control were recruited. Serum leptin was measured. Patients were genotyped for three SNPs in the LEP gene (rs7799039, rs2167270, and rs791620). Results: Serum leptin was significantly lower in T2DM patients with poor glycemic control (p < 0.05). In multivariate analysis, serum leptin levels significantly lowered the risk of having poor glycemic control (OR = 0.985; CI: 0.976-0.994; p = 0.002); moreover, the GA genotype of rs2167270 was protective against poor glycemic control compared to the GG genotype (OR = 0.417; CI: 0.245-0.712; p = 0.001). Conclusions: Higher serum leptin and the GA genotype of the rs2167270 SNP of the LEP gene were associated with good glycemic control in T2DM patients on metformin therapy. Further studies with a larger sample size from multiple institutions are required to validate the findings.

Does four-week consecutive, dawn-to-sunset intermittent fasting during Ramadan affect cardiometabolic risk factors in healthy adults? A systematic review, meta-analysis, and meta-regression.

AIMS: This study aimed to evaluate the effects of Ramadan diurnal intermittent fasting (RDIF; 29-30 days) on cardiometabolic risk factors (CMRF) in healthy adults, and examine the effect of various cofactors on the outcomes using sub-group meta-regression. DATA SYNTHESIS: We conducted a systematic review and meta-analysis to measure the effect sizes of changes in CMRF in healthy adult Muslims observing RDIF. Ten scientific databases (EBSCOhost, CINAHL, Cochrane, EMBASE, PubMed/MEDLINE, Scopus, Google Scholar, ProQuest Medical, ScienceDirect, and Web of Science) were searched from the date of inception (1950) to the end of November 2020. The CMRF searched and analyzed were total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), diastolic blood pressure (DBP), and heart rate (HR). We identified 91 studies (4431 adults aged 18-85 years) conducted between 1982 and 2020 in 23 countries distributed over four continents. RDIF-induced effect sizes for CMRF were: TC (no. of studies K = 77, number of subjects N = 3705, Hedge's g = -0.092, 95% confidence interval (CI): -0.168, 0.016); TG (K = 74, N = 3591, Hedge's g = -0.127, 95% CI: -0.203, 0.051); HDL-C (K = 68, N = 3528, Hedge's g = 0.138, 95% CI: 0.051, 0.224); LDL-C (K = 65, N = 3354, Hedge's g = -0.115, 95% CI: -0.197, -0.034); VLDL-C (K = 13, N = 648, Hedge's g = -0.252, 95% CI: -0.431, 0.073), DBP (K = 32, N = 1716, Hedge's g = -0.255, 95% CI: -0.363, 0.147), and HR (K = 12, N = 674, Hedge's g = -0.082, 95% CI: -0.300, 0.136). Meta-regression revealed that the age of fasting people was a significant moderator of changes in both HDL-C (P = 0.02) and VLDL-C (P = 0.01). Male sex was the only significant moderator of changes in LDL-C (P = 0.055). Fasting time duration was the only significant moderator of HDL-C (P = 0.001) at the end of Ramadan. CONCLUSIONS: RDIF positively impacts CMRF, which may confer short-term transient protection against cardiovascular disease among healthy people.

Eating disorders risk among medical students: a global systematic review and meta-analysis.

PURPOSE: Medical students appear to be a high-risk group to develop psychological problems including eating disorders (ED). The prevalence estimates of ED risk vary greatly between studies. This systematic review and meta-analysis was done to estimate the prevalence of ED risk among medical students. METHODS: An electronic search of EMBASE, MEDLINE, ProQuest and Google Scholar was conducted. Studies that reported the prevalence of ED risk among medical students and were published in English peer-reviewed journals between 1982 and 2017 were included. Information about study characteristics and the prevalence of ED risk were extracted by four investigators. Each article was reviewed independently by at least two investigators. Estimates were pooled using random-effects meta-analysis using the DerSimonian-Laird method. The main outcome of interest was the prevalence of ED risk in medical students. RESULTS: The prevalence of ED risk among medical students was extracted from nineteen cross-sectional studies across nine countries (total participants n = 5722). The overall pooled prevalence rate of ED risk was 10.4% (497/5722 students, 95% CI 7.8-13.0%), with statistically significant evidence between-study heterogeneity (Q = 295, τ2 = 0.003, I2 = 94.0%, P < 0.001). Prevalence estimates between studies ranged from 2.2 to 29.1%. CONCLUSION: In this systematic review and meta-analysis, the summary prevalence of ED risk among medical students was 10.4%. Further research is needed to identify and prevent ED in this population. Studies are also needed to investigate concurrent pathologies associated with ED risk. LEVEL OF EVIDENCE: Level I, systematic review and meta-analysis.

Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage.

STUDY QUESTION: Is recurrent spontaneous miscarriage (RSM) associated with changes in vascular endothelial growth factor (VEGF) serum levels, and with polymorphisms in the VEGFA gene? SUMMARY ANSWER: Reduced serum VEGF levels, and VEGFA -460T/C (rs833061), 398G/A (rs833068), -583T/C (rs3025020) variants, were associated with RSM. WHAT IS KNOWN ALREADY: Reduced expression of VEGF has been linked with spontaneous miscarriage, likely due to defective fetal and placental angiogenesis. Since VEGF production is in part inherited, VEGFA polymorphisms associated with altered VEGF secretion have been investigated for their association with RSM, often with variable conclusions. STUDY DESIGN, SIZE, DURATION: A retrospective case-control study, which was conducted between January 2011 and April 15, 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects comprised 296 women with RSM (mean age: 31.6 ± 5.4 year), and 305 age-matched (mean age: 31.6 ± 4.9 year) control Arab women, who had attended outpatient obstetrics and gynecology clinics in two teaching hospitals in Bahrain. VEGFA -2578C/A (rs699947), -460T/C (rs833061), -1154G/A (rs15703060), -634G/C (rs2010963), 398G/A (rs833068), 497G/A (rs833070), -583T/C (rs3025020) and 936C/T (rs3025039) genotyping was done by real-time PCR, with defined clusters; VEGF serum levels were measured by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: Higher minor allele frequency (MAF) and genotype distribution of -460T/C [corrected P (Pc) = 0.003], 398G/A (Pc = 0.016) and -583T/C (Pc < 0.001) single nucleotide polymorphisms (SNPs) were seen in RSM cases than control women. Increased RSM risk was seen with homozygous -460T/C and 398G/A SNPs and with heterozygous -583T/C, which had a stronger effect when homozygous. Serum VEGF levels were significantly reduced in RSM cases compared with control women (P = 0.016), and correlated with -460T/C, 398G/A and -583T/C genotypes. Haploview analysis revealed heterogeneity in linkage disequilibrium between VEGFA variants, and two blocks were identified: Block 1 comprising -2578C/A, -460T/C and -1154G/A, while Block 2 contained -634G/C, 398G/A, 497G/A, -583T/C and 936C/T. Both negatively and positively RSM-associated 3-locus (Block 1) and 5-locus (Block 2) VEGFA haplotypes were identified, after controlling for a number of covariates. LIMITATIONS, REASONS FOR CAUTION: The study was retrospective and can only demonstrate association and not a cause-effect relationship. Furthermore, it was limited to Bahraini Arabs,thereby necessitating parallel studies on other ethnic groups. WIDER IMPLICATIONS OF THE FINDINGS: Reduced VEGF secretion, and specific VEGFA variants may contribute to the pathogenesis of RSM. However, the association of VEGFA SNPs with RSM appears to be independent of their association with altered VEGF serum levels. The differential association of VEGFA variants with RSM is in line with previous findings on the contribution of ethnicity/racial background to genetic association studies.

Plasma IL-6, TREM1, uPAR, and IL6/IL8 biomarkers increment further witnessing the chronic inflammation in type 2 diabetes.

OBJECTIVES: Type 2 diabetes (T2D) is known to be associated with chronic inflammation, but the inflammatory regulators/markers are not exactly defined and the link between them remains undetermined. The objective of this study is to identify these markers by testing traditional (IL6 & IL8) and non-traditional (TREM1 & uPAR) inflammatory markers. METHODS: Data and blood samples were obtained from 114 T2D and 74 non-diabetic Kuwaiti subjects attending health facilities in Kuwait. Chemical analyzers were used to measure glycemic and lipid profiles, while ELISA was used to measure plasma levels of insulin and several inflammatory markers. RESULTS: Showed that the IL-6 and TREM1 were significantly higher in T2D compared to non-diabetic controls, and the uPAR level was borderline higher in T2D but significantly correlated with IL-6 levels. Unexpectedly, IL8 was significantly below normal in T2D and IL6/IL8 ratio was significantly higher in T2D patients. Unlike other tested markers, uPAR was in addition strongly correlated with insulin levels and HOMA-IR index. CONCLUSIONS: Raised levels of IL6, TREMI, IL6/IL8 ratio, and the strong positive correlation of plasma levels of uPAR with IL-6, insulin, and HOMA-IR index, are reliable spectators of chronic inflammation in T2D patients. The reduced level of IL-8 in T2D was a peculiar observation that needs further explanation. Finally, the consequences and impact of the sustained rise of these inflammatory regulators in diabetic tissues need to be meticulously explored.

Protein Z polymorphisms associated with vaso-occlusive crisis in young sickle cell disease patients.

We investigated the association of protein Z (PZ) promoter (rs3024718, rs3024719, and rs3024731) and intron (rs3024735; G79A) SNPs with sickle cell disease (SCD) vaso-occlusive crisis (VOC). Study subjects included 239 SCD patients with VOC and 138 pain-free SCD control patients. PZ genotyping was done by allelic discrimination (real-time PCR) assays. The minor allele frequency of rs3024718 (P=0.03), rs3024719 (P=0.02), rs3024731 (P<0.001), and rs3024735 (P<0.001) were higher in VOC patients than control SCD patients. Significant differences in the distribution of rs3024731 (P=0.028) and rs3024735 (P=0.045) genotypes were seen between VOC and steady-state SCD patients. This association remained significant after adjusting for gender, HbS, and HbF. Four-locus (rs3024718/rs3024719/rs3024731/rs3024735) PZ haplotypes analysis demonstrated increased frequency of GAAA (P=0.024), AGAA (P=0.011), and GGTG (P=0.002), and reduced frequency of AGTG haplotype (P=0.001) in VOC than in steady-state control patients, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. Of these, only AGTG (P(c)=0.001) and GGTG (P(c)=0.018) remained significant after applying the Bonferroni correction. In conclusion, specific PZ variants and haplotypes are significantly associated with SCD VOC.

The relation of vascular endothelial growth factor (VEGF) gene polymorphisms on VEGF levels and the risk of vasoocclusive crisis in sickle cell disease.

OBJECTIVE: The association of vascular endothelial growth factor (VEGFA) variants and VEGF secretion with sickle cell disease (SCD) vasoocclusive crisis (VOC) was investigated in 210 VOC patients and 114 pain-free control patients. METHODS: VEGFA -2578C/A (rs699947), -460T/C (rs833061), -1154G/A (rs15703060), -634G/C (rs2010963), 398G/A (rs833068), 497G/A (rs833070), -583T/C (rs3025020), and 936C/T (rs3025039) were carried out by real-time PCR. RESULTS: Higher frequency of rs2010963 C-allele, rs833068 A-allele, and rs3025020 C-allele and significant differences in rs2010963, rs833068, and rs3025020 genotype distribution were seen in VOC than steady-state patients. Increased VOC risk was seen with rs2010963 as heterozygous and more as homozygous, and in rs833068 and rs3025020 homozygous carriers. While there were no differences in VEGF levels between VOC and steady-state controls, there was a progressive decline in serum VEGF in rs2010963 and rs833068 heterozygous and homozygous genotypes, but an opposite trend was seen in VOC patients. Haploview analysis revealed high LD between rs699947, rs833061, rs1570360, rs2010963, rs833068, and rs833070, but weak or no LD between rs3025020 and rs3025039 and other SNPs. Six-locus (rs699947/rs833061/rs1570360/rs2010963/rs833068/rs833070) VEGFA haplotype analysis identified haplotype 111111 to be negatively (OR = 0.68) and haplotype 111222 to be positively (OR = 1.89) associated with VOC. rs2010963, rs833068, and rs3025020 were correlated with VOC type, while rs3025020 was correlated with hospitalization, VOC treatment, and duration. CONCLUSION: Specific VEGFA variants contribute to the pathogenesis of SCD VOC.

Diabetic sarcopenia: metabolic and molecular appraisal.

Myopathy is the missing slot from the routine clinical checkup for diabetic complications. Similarly, its pathophysiological, metabolic, and molecular bases are insufficiently explored. In this review, the above issues are highlighted with a focus on skeletal muscle atrophy (also described as diabetic sarcopenia), in contrast to the normal histological, physiological, and molecular features of the muscles. Literature search using published data from different online resources was used. Several diabetic myopathy etiological factors are discussed explicitly including; inflammation and immunological responses, with emphasis on TNFα and IL-6 overproduction, oxidative stress, neuropathy and vasculopathy, aging sarcopenia, antidiabetic drugs, and insulin resistance as a denominator. The pathophysiological hallmark of diabetic muscle atrophy is the decreased muscle proteins synthesis and increased degradation. The muscle protein degradation is conveyed by 4 systems; ubiquitin-proteasome, lysosomal autophagy, caspase-3, and calpain systems, and is mostly mediated via the IL6/STAT, TNF&IL6/NFκB, myostatin/Smad2/3, and FOXO1/3 signaling pathways, while the protein synthesis inhibition is mediated via suppression of the IGF1-PI3K-Akt-mTOR, and SC-Gαi2-pathways. Moreover, the satellite cells and multilineage muscle mesenchymal progenitor cells differentiation plays a major role on the fate of the affected muscle cells by taking an adipogenic, fibrogenic, or connective tissue lineage. As a conclusion, in this article, the pathological features of diabetic sarcopenia are reviewed at gross level, while at a molecular level the normal protein turnover, signal transduction, and pathways involved in muscle atrophy are described. Finally, an integrated network describing the molecular partakers in diabetic sarcopenia is presented.

Diabetes mellitus tendino-myopathy: epidemiology, clinical features, diagnosis and management of an overlooked diabetic complication.

Tendino-myopathy, an unexplored niche, is a non-vascular unstated T2DM complication, which is largely disregarded in clinical practice, thus, we aim to explore it in this review. Literature search using published data from different online resources. Epidemiologically, reported prevalence varies around 10-90%, which is marked variable and unreliable. Clinically, diabetic tendino-myopathy is typified by restriction of movement, pain/tenderness, cramps and decreased functions. Moreover, myopathy is characterized by muscle atrophy, weakness and ischemia, and tendinopathy by deformities and reduced functions/precision. In tendonapthy, the three most affected regions are: the hand (cheiroarthropathy, Dupuytren's contracture, flexor tenosynovitis and carpel tunnel syndrome), shoulder (adhesive capsulitis, rotator cuff tendinopathy and tenosynovitis) and foot (Achilles tendinopathy with the risk of tear/rupture), in addition to diffuse idiopathic skeletal hyperostosis. Pathologically, it is characterized by decreased muscle fiber mass and increased fibrosis, with marked extracellular matrix remodeling and deposition of collagens. The tendon changes include decreased collagen fibril diameter, changed morphology, increased packing and disorganization, with overall thickening, and calcification. Diagnosis is basically clinical and radiological, while diagnostic biomarkers are awaited. Management is done by diabetes control, special nutrition and physiotherapy, while analgesics, steroids and surgery are used in tendinopathy. Several antisarcopenic drugs are in the pipeline. This review aims to bridge clinical practice with research and update routine diabetic checkup by inclusion of tendino-myopathies in the list with an emphasis on management.

Anti-annexin V IgG and IgM antibodies in sickle cell disease patients with vaso-occlusive crisis.

Vaso-occlusive crisis (VOC) is a significant cause of morbidity and mortality in sickle cell anemia (SCA) patients; however, its mechanisms are poorly understood. In view of their prothrombotic nature, we hypothesized that SCA-associated VOC may be due to the presence of anti-annexin V antibodies. Anti-annexin V antibodies were measured with ELISA in 177 VOC and 81 steady-state SCA patients. Anti-annexin V IgM and IgG concentrations were significantly higher in VOC patients than in steady-state patients and were associated with elevated VOC risk. After categorizing anti-annexin V antibodies, the adjusted odds ratio increased as the percentile value increased. Monovariate logistic regression analysis demonstrated a positive dose-effect relationship for anti-annexin V IgM with VOC, with increased VOC risk seen with increased antibody titers. Multivariate logistic regression analyses confirmed the association of anti-annexin V IgM, more so than IgG, as an independent VOC risk factor. Anti-annexin V IgG antibodies correlated positively with VOC type and negatively with HbF and age of VOC onset, while anti-annexin V IgM correlated positively with VOC type, duration, frequency, site, pain severity, hospitalization, and medication, and negatively with age of VOC onset and HbS levels. High levels of anti-annexin V IgM antibodies constitute a risk factor for VOC in SCA patients.

Influence of CYP2C9, VKORC1, and CYP4F2 polymorphisms on the pharmacodynamic parameters of warfarin: a cross-sectional study.

BACKGROUND: Warfarin is the most commonly evaluated drug in pharmacogenetic-guided dosing studies. However, gaps remain regarding the influence of the genetic polymorphisms of CYP2C9, VKORC1, and CYP4F2 on specific pharmacodynamic parameters like the warfarin sensitivity index (WSI), prothrombin time international normalized ratio (PT-INR), and log-INR variability. METHODS: A cross-sectional study was conducted in non-smoking adults receiving warfarin for at least 6 months. Their demographics, diagnoses, warfarin dosing regimen, concomitant drugs, PT-INR, and bleeding episodes were obtained. CYP2C9 (rs1057910-*3 and rs1799853-*2 alleles), CYP4F2 (rs2108622), and VKORC1 (rs9923231) polymorphisms were assessed using real-time polymerase chain reaction. Three genotype groups (I-III) were defined based on the combined genetic polymorphisms of CYP2C9 and VKORC1 from the FDA's recommendations. Key outcome measures included anticoagulation control, time spent in therapeutic range, stable warfarin dose, WSI, log-INR variability, and Warfarin Composite Measure (WCM). RESULTS: The study recruited 236 patients; 75 (31.8%) carried a functional CYP2C9 variant allele, and, 143 (60.6%) had at least one T allele in CYP4F2 and 133 (56.4%) had at least one T allele in VKORC1. Groups' II and III CYP2C9 and VKORC1 genotypes were observed with reduced stable warfarin dose, increased WSI, higher log-INR variability, and increased bleeding risk. The presence of *2 or *3 allele in CYP2C9 was observed with reduced stable warfarin doses akin to the presence of T alleles in VKORC1; however, the doses increased with T alleles in CYP4F2. CONCLUSION: The evaluated genetic polymorphisms significantly influenced all the pharmacodynamic parameters of warfarin. Evaluating CYP2C9, VKORC1, and CYP4F2 genetic polymorphisms prior to warfarin initiation is likely to optimize therapeutic response.

The influence of TERC, TERT and ACYP2 genes polymorphisms on plasma telomerase concentration, telomeres length and T2DM.

Telomeres are duplex tandem repeats of DNA sequence 5'-TTAGGG-3' at chromosomal ends synthesized by telomerase enzyme (TE). Telomeres length (TL) shortening is associated with age and age-related disorders. Recently, we demonstrated marked leukocytes TL (LTL) shortening in T2DM. To set the relationship between the TE, LTL and T2DM, we analyzed samples from 212 Kuwaiti subjects, 112 patients withT2DM and 100 non-diabetic subjects. The plasma TE and fasting insulin were measured by ELISA, the LTL was estimated by qPCR and three SNPs of genes related to TL; TERC rs12696304 (C/G), TERT rs2736100 (C/A) and ACYP2 rs6713088 (C/G) were genotyped by rtPCR. Results revealed comparable TE levels and alleles/genotypes between the cases and controls with no influence of either on the LTL. Interestingly, although the plasma concentration of the TE was generally low, it was significantly influenced by the TERT and ACYP2 but not TERC polymorphisms. The CC genotype carriers of rs2736100 (C/A) had significantly higher plasma TE levels compared to CA and AA carriers, p 0.009 and p 0.047, respectively, and the A-allele was associated with low TE, p 0.018. Similarly, significantly higher TE levels were detected in CC carriers of ACYP2 rs6713088 (C/G) compared with GC carriers, p 0.002, and the G-allele was associated with low TE, p 0.009. Finally, the TERT and ACYP2 polymorphisms had an influence on blood glucose levels. In conclusion, the telomeres shortening in T2DM was not due to TE deficiency or gene polymorphisms, while the TE levels were significantly associated with the TERT and ACYP2 but not TERC polymorphisms.

Analogous telomeres shortening and different metabolic profile: hypertension versus hypertension/type 2 diabetes mellitus comorbidity.

BACKGROUND: Eukaryotes chromosomal ends are capped and protected by telomeres, which are noncoding DNA repeats synthesized by telomerase enzyme. The telomerase enzyme is a nucleoprotein encoded by TERC and TERT genes. Naturally, the length of the telomeres shortens with each cell cycle but the shortening is fastened in certain age-related diseases like hypertension (HTN) and type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Blood samples (n = 171) were obtained from Kuwaiti subjects with HTN, and HTN/T2DM comorbidity (HTN-DM) and healthy subjects. The leukocyte telomere length (LTL) was measured by SYBR green quantitative rtPCR, and plasma telomerase enzyme was measured by ELISA, in addition, three single nucleotide polymorphisms (SNPs) in telomere-related genes; TERC rs12696304GC, TERT rs2736100CA, and ACYP2 rs6713088GC were genotyped by real-time PCR. RESULTS: Marked LTL shortening in subjects with HTN and HTN-DM compared to healthy subjects, P = 0.043 and P < 0.001, respectively, was noticed. On the contrary, the plasma telomerase enzyme levels and minor allele frequencies and genotypes of the tested SNPs were comparable between the study groups, except for TERT (CA) genotype which was over-represented in HTN (P = 0.037). Furthermore, the comparisons between HTN and HTN-DM revealed significantly higher total cholesterol (P = 0.015) and LDL-C (P = 0.008) in HTN, while higher insulin levels (P < 001), HOMA-IR (P < 001), and BMI (P = 0.004) were observed in HTN-DM. CONCLUSION: This study showed comparable LTL shortening in HTN and HTN-DM, irrespective of plasma telomerase enzyme levels or tested TERC, TERT, and ACYP2 gene polymorphisms, although HTN and HTN-DM differed in several metabolic markers. More studies are required to affirm these observations.

The relation of C-reactive protein to vasoocclusive crisis in children with sickle cell disease.

In view of evidence linking sickle cell anemia (SCA) with chronic inflammation, and given the role of high sensitivity C-reactive protein (hs-CRP) as inflammatory mediator, we hypothesized that SCA vasoocclusive crisis (VOC) is associated with heightened hs-CRP levels. Study subjects comprised 104 SCA patients who experienced VOC event during the study period (VOC group), and 40 SCA patients who did not develop VOC for at least 9 months prior to blood collection (Steady-state group). hs-CRP determination was done by latex-enhanced nephelometry. Higher hs-CRP levels were seen in VOC [median(range)=31.3(1.14-363.0)] than steady-state [median(range)=5(0.16-185.0)] groups (P<0.001), with enrichment in high hs-CRP percentiles in VOC cases, which translated into step-wise increased VOC risk. Receiver-operating characteristic (ROC) analysis was employed in assessing the usefulness of hs-CRP as predictor of the frequency and severity of VOC. Spearman's correlation coefficient between hs-CRP and VOC was 0.65 (P<0.001) among unselected patients (0.71 in males and 0.59 in females). hs-CRP area under ROC curves was 0.90 (95% CI=0.85-0.94) among unselected patients, 0.94 (95% CI=0.89-0.98) for males, and 0.85 (95% CI=0.77-0.93) for females. Logistic regression analysis confirmed the positive association of increased hs-CRP levels with VOC, which correlated positively with VOC frequency (P<0.001), type (P<0.001), pain (P<0.001), and need for hospitalization (P=0.024). These data support strong association of increased hs-CRP levels with VOC, which impacts VOC-related parameters, and support a role for hs-CRP in VOC follow-up.

The prevalence of absence of the palmaris longus muscle in the Bahraini population.

Absence of the palmaris longus muscle has been well documented in several populations at a prevalence rate ranging between 2.2 and 63.9% which varies according to race, sex, and side of the body. There is little documentation of the prevalence of absence of this muscle from populations in the Arabian Gulf region. We examined 1,043 subjects, 3-85 years old, from the Kingdom of Bahrain for the presence or absence of the palmaris longus muscle using the conventional test for the presence of this muscle. Statistical analyses investigated the association of muscle absence with sex, hand dominance, and laterality. The palmaris longus muscle was absent in 36.8% of subjects. Bilateral absence (19%) was more common than unilateral absence (17.9%) with preponderance in female subjects. The muscle was absent more often on the left side than the right (P = 0.003). In the right upper limbs the muscle was absent in female subjects more than male subjects (P = 0.031). This study reaffirms that there is population variation in the frequency of absence of the palmaris longus muscle. The tendon of the palmaris longus bifurcated at the wrist in 7.1% of subjects, with male subjects showing this feature more frequently than female subjects in the right hand (P = 0.037) and the left hand (P = 0.030). This has not been reported before. The clinical significance of our findings is discussed.

Shortening of the leucocytes' telomeres length in T2DM independent of age and telomerase activity.

AIMS: This study aimed to examine the role of plasma telomerase (TE), plasma insulin, patient's age and disease duration in determination of the leucocytes' telomeres length (LTL) in T2DM. METHODS: Blood samples from Kuwaiti patients with T2DM (110) and non-diabetic subjects (94) were analyzed by SYBR Green Quantitative PCR for estimation of the Absolute Human Telomere Length and by ELISA for estimation of the TE activity and insulin level. The body mass index (BMI) and HOMA-IR were calculated. RESULTS: The results revealed marked shortening of the LTL in T2DM compared with the non-diabetic subjects (6.068, 2.276-11.652 vs. 10.979, 6.495-23.402 kb), p < 0.001, while the TE concentration was comparable between the two groups (3.16, 0.00-6.02 vs. 4.16, 1.38-7.94 U/L, respectively), p 0.100. Importantly, in T2DM the LTL did not vary significantly with the disease duration (1 month to 40 years), p 0.959, and did not correlate with age, BMI, insulin-resistance, or glycemic parameters. Interestingly, there was a positive correlation between the LTL and insulin levels in T2DM (CC 0.211, p 0.0419). Finally, in non-diabetic subjects, HbA1c ≥ 6% was associated significantly with shorter LTL, this observation together with the lack of association of the LTL with the disease duration, suggests a causal role of short telomeres in T2DM development. CONCLUSIONS: This study confirmed the LTL shortening in T2DM in Kuwaiti Arabs, and showed that the LTL was independent of age and TE activity but positively influenced by insulin levels. Furthermore, the study suggested that telomeres shortening could be a risk factor for T2DM.

Protein Z variants associated with protein Z plasma levels and with risk of idiopathic recurrent miscarriage.

Protein Z (PZ) deficiency due to anti-PZ autoantibodies and/or mutations in PZgene was linked with adverse pregnancy outcomes, including idiopathic recurrent miscarriage (IRM). We investigated the association of rs3024718, rs3024719, rs3024731, rs3024778, rs3024772, and rs3024735 (G79A) PZ variants and changes in PZ levels in 287 women with IRM, and 308 control women. Of the 6 single nucleotide polymorphisms (SNPs) analyzed, higher minor allele frequency of rs3024735 (G79A) and rs3024731 were seen in IRM cases than in control women. Significantly higher frequencies of rs3024735/G79A G/A and A/A (P< .001), rs3024719 G/A (P= .009), and rs3024731 A/A (P = .012), but not rs3024718 (P= .12), rs3024778 (P = .76), or rs3024772 (P= .27) genotype carriers were seen between IRM cases versus control women, respectively, and was linked with reduced PZ levels. Six-locus (rs3024718/rs3024719/rs3024778/rs3024731/rs3024735/rs3024772) PZhaplotypes analysis demonstrated increased frequency of GAGAAG and AGGTAG and reduced frequency of AGGTGC haplotypes in IRM cases, thereby conferring disease susceptibility and protective nature to these haplotypes, respectively. These results demonstrate that specific PZSNPs and haplotypes are significantly associated with IRM.

Anti-phosphatidylserine, anti-cardiolipin, anti-ß2 glycoprotein I and anti-prothrombin antibodies in recurrent miscarriage at 8-12 gestational weeks.

OBJECTIVE: To investigate the association of antibodies to ß2-glycoprotein I (anti-ß2GPI), cardiolipin (ACA), phosphatidylserine (anti-PS) and prothrombin (anti-PT) with recurrent spontaneous miscarriage (RSM). STUDY DESIGN: Case-control study involving 277 RSM cases and 288 controls: autoantibody levels were measured by ELISA. Differences between cases and controls were analyzed by nonparametric Mann-Whitney test, and logistic regression was used in analyzing the association of autoantibodies with RSM. RESULTS: Anti-PS IgG, ACA IgM and IgG, and anti-PT IgM were significantly associated with RSM risk, and differential antibody association was noted according to BMI and primary and secondary RSM. Higher prevalence of elevated anti-PS IgG was seen in cases, with the strongest risk above the 99th percentile. For ACA IgM, 28 cases (10.1%) and 5 controls (1.7%) were positive, with increasing OR for increasing cut-off points, which was significant at antibody titers >99th percentile. For ACA IgG, 101 cases (36.5%) and 13 controls (4.5%) were positive, with graded increase in OR for increasing cut-off points, which was significant at titers >90th percentile (maximal at titers >99th percentile). For anti-PT, 23 cases (12.0%) and 9 controls (6.1%) were positive, with increased OR at titers >90th percentile. Regression analyses confirmed the independent association of anti-PS IgG, ACA IgM and IgG with RSM, and significant RSM risk was associated with high anti-PS IgG (P<0.001) and ACA IgM (P<0.001) titers, and a dose-dependent increase in RSM risk was seen with progressively increased ACA IgG titers. No significant association existed between anti-PT IgM and RSM. CONCLUSION: Elevated ACA IgM and IgG, and anti-PS IgG antibodies are positively associated with RSM.

Replication study of common variants in CDKAL1 and CDKN2A/2B genes associated with type 2 diabetes in Lebanese Arab population.

We investigated the association of CDKAL1 (rs7754840 and rs7756992) and CDKN2A/2B (rs10811661) variants with T2DM. Higher MAF of rs7754840 and rs7756992 were seen in patients, and both were associated with T2DM under additive, dominant, and recessive models. CDKAL1 rs7754840 and rs7756992, but not CDKN2A/2B rs10811661, are associated with T2DM in Lebanese.

Effect of the functional VEGFA-583C/T variant on vascular endothelial growth factor levels and the risk of recurrent spontaneous miscarriage.

The association of vascular endothelial growth factor (VEGF) -583C/T variant with recurrent miscarriage (RSM) was investigated in 173 RSM cases and 248 control women. Increased minor allele and genotype frequencies of -583C/T, and reduced serum VEGF concentrations were associated with increased risk of RSM.