Gut-Derived Endotoxin and Telomere Length Attrition in Adults with and without Type 2 Diabetes.

Premature aging, as denoted by a reduced telomere length (TL), has been observed in several chronic inflammatory diseases, such as obesity and type 2 diabetes mellitus (T2DM). However, no study to date has addressed the potential inflammatory influence of the gut-derived Gram-negative bacterial fragments lipopolysaccharide, also referred to as endotoxin, and its influence on TL in low-grade inflammatory states such as type 2 diabetes mellitus (T2DM). The current study therefore investigated the influence of endotoxin and inflammatory factors on telomere length (TL) in adults with (T2DM: n = 387) and without (non-diabetic (ND) controls: n = 417) obesity and T2DM. Anthropometric characteristics were taken, and fasted blood samples were used to measure biomarkers, TL, and endotoxin. The findings from this study highlighted across all participants that circulating endotoxin (r = -0.17, p = 0.01) was inversely associated with TL, noting that endotoxin and triglycerides predicted 18% of the variance perceived in TL (p < 0.001). Further stratification of the participants according to T2DM status and sex highlighted that endotoxin significantly predicted 19% of the variance denoted in TL among male T2DM participants (p = 0.007), where TL was notably influenced. The influence on TL was not observed to be impacted by anti-T2DM medications, statins, or anti-hypertensive therapies. Taken together, these results show that TL attrition was inversely associated with circulating endotoxin levels independent of the presence of T2DM and other cardiometabolic factors, suggesting that low-grade chronic inflammation may trigger premature biological aging. The findings further highlight the clinical relevance of mitigating the levels of circulating endotoxin (e.g., manipulation of gut microbiome) not only for the prevention of chronic diseases but also to promote healthy aging.

Vitamin D Receptor Gene Variants Susceptible to Osteoporosis in Arab Post-Menopausal Women.

Post-menopausal osteoporosis (PMO) is a multifactorial bone disorder in elderly women. Various vitamin D receptor (VDR) gene variants have been studied and associated with osteoporosis in other populations, but not in a homogenous Arab ethnic group. Herein, the current study explores the association between VDR polymorphisms and susceptibility to osteoporosis in Saudi postmenopausal women. In total, 600 Saudi postmenopausal women (N = 300 osteoporosis; N = 300 control) were genotyped for VDR gene variants (rs7975232, rs1544410, rs731236) using TaqMan® SNP genotyping assays. Bone mineral density (BMD) for the lumbar spine and femur was assessed using dual-energy X-ray absorptiometry (DEXA). The heterozygous frequency distributions AC of rs7975232, CT of rs1544410, and AG of rs731236 were significantly higher in the osteoporosis group than controls (p < 0.05). Heterozygous AC of rs7975232 (1.6; 95% CI 1.1-2.3; p < 0.023), CT of rs1544410 (1.6; 95% CI 1.1-2.4; p < 0.022), and AG of rs731236 (1.6; 95% CI 1.1-2.4; p < 0.024) were significantly associated with increased risk of osteoporosis, independent of age and BMI. In conclusion, VDR gene variants rs7975232, rs1544410, rs731236 had a significant effect on BMD and were associated with osteoporosis risk in Saudi postmenopausal women.

Vitamin D Metabolites and Sex Steroid Indices in Postmenopausal Women with and without Low Bone Mass.

While the independent roles of vitamin D and sex hormones in skeletal health are well established, the associations of vitamin D and its metabolites to sex hormones and their indices are less investigated. In this observational study, clinical information of 189 Saudi postmenopausal women aged ≥50 years old [N = 80 with normal bone mineral density (BMD), aged 53.3 ± 7.7 years with body mass index (BMI)= 34.1kg/m2 ± 5.8, and N = 109 with low BMD (T-score -1.0 to -2.5), aged 57.0 ± 8.2 years, BMI = 32.4kg/m2 ± 6.2] was extracted from an existing capital-wide osteoporosis registry in Riyadh, Saudi Arabia. Data included were BMD scores, serum total 25(OH)D, sex hormones, and bone turnover markers which were measured using commercially available assays. Age- and BMI-adjusted comparisons revealed significantly higher parathyroid hormone (PTH) levels as well as significantly lower testosterone and bioavailable testosterone in the low BMD group than the normal BMD group (p-values 0.04, 0.02, and 0.03, respectively). Stepwise linear regression showed that circulating testosterone levels accounted for 9.7% and 8.9% of the variances perceived in bioavailable 25(OH)D and free 25(OH)D, respectively (p < 0.01), independent of other sex hormones, sex hormone indices, and bone turnover markers. Our study suggests that androgens are significantly associated with non-conventional vitamin D metabolites and these associations may have clinical relevance in assessing risk for low BMD and osteoporosis in Arab postmenopausal women.

ABCA1 C69T gene polymorphism and risk of type 2 diabetes mellitus in a Saudi population.

Type 2 diabetes mellitus (T2DM) is a disease induced by complex interactions between environmental factors and certain genetic factors. Genetic variants in the Adenosine Binding Cassette Transporter Proteins 1 (ABCA1) have been associated with abnormalities of serum lipid levels of high-density lipoprotein (HDL-C). Decreased serum levels of HDL-C have often been observed in T2DM cases, and this condition has been considered to be involved in the mechanism of insulin resistance (IR). Therefore, we investigated possible association between ABCA1 C69T gene polymorphism and T2DMin a Saudi population. This study was carried out with 380 healthy control subjects and 376 T2DM patients. Genotyping of ABCA1 C69T polymorphism was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique. We observed that the frequency of the T allele of the ABCA1 C69T gene was significantly higher in healthy subjects compared to T2DMpatients (0.28 vs 0.45; p less than 0.0001; OR (95 percent CI) = 0.4624 (0.3732-0.5729), and therefore the T allele may be a protective factor against T2DM in the Saudi population.