The aim of this trial was to characterize the beneficial effects of probiotics on decreasing endotoxin levels and other cardiometabolic parameters in Arab patients with type 2 diabetes mellitus ...(T2DM).
Saudi adults with naïve T2DM (n = 30; 12 males and 18 females) were randomly allocated to receive twice daily placebo or 2.5 × 109 cfu/g of Ecologic®Barrier (multi-strain probiotics; n = 31; 14 males and 17 females) in a double-blind manner over a 6 month period, respectively. Anthropometrics were measured and fasting blood samples were collected to analyze endotoxin, glycemic parameters glucose, insulin, c-peptide and homeostasis model assessment for insulin resistance (HOMA-IR), lipids triglycerides, total cholesterol, low and high-density lipoprotein (LDL and HDL, respectively) cholesterol and total/HDL-cholesterol ratio, inflammatory markers tumor-necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) and adipocytokines leptin, adiponectin and resistin at baseline and after 3 and 6 months of intervention.
Multi-strain probiotics supplementation for 6 months caused a significant decrease in circulating levels of endotoxin by almost 70% over 6 months, as well as glucose (38%), insulin (38%), HOMA-IR (64%), triglycerides (48%), total cholesterol (19%), total/HDL-cholesterol ratio (19%), TNF-α (67%), IL-6 (77%), CRP (53%), resistin (53%), and a significant increase in adiponectin (72%) as compared with baseline. Only HOMA-IR had a clinically significant reduction (−3.4, 64.2%) in the probiotics group as compared to placebo group at all time points. No other clinically significant changes were observed between the probiotic or placebo group at 3 and 6 months in other markers.
Multi-strain probiotic supplementation over 6 months as a monotherapy significantly decreased HOMA-IR in T2DM patients, with the probiotic treatment group highlighting reduced inflammation and improved cardiometabolic profile. As such, multi-strain probiotics is a promising adjuvant anti-diabetes therapy.
ClinicalTrials.gov Identifier: NCT01765517.
There is conflicting evidence on the favorable effects of vitamin D supplementation on metabolic profile in Type 2 diabetes mellitus (T2DM) patients and this might be due to genetic variations in ...vitamin D receptors (VDRs). Thus, we studied the metabolic effects of a 12-month vitamin D supplementation in T2DM patients according to VDR polymorphisms. A total of 204 T2DM subjects received 2000 IU vitamin D3 daily for 12 months. Serum 25(OH)D and metabolic profiles were measured at baseline and after 12 months. VDR polymorphisms (Taq-I, Bsm-I, Apa-I and Fok-I) were identified using TaqMan genotyping assays. Vitamin D supplementation significantly increased HOMA β-cell function (p = 0.003) as well as significantly decreased triglycerides, total and LDL-cholesterol (p < 0.001). The lowest increment in 25(OH)D levels was detected in patients with Fok-I CC genotypes (p < 0.0001). With vitamin D supplementation, Taq-I GG genotype carriers showed significant improvements in triglycerides, LDL- and total cholesterol, insulin, HbA1c and HOMA-IR (p < 0.005, 0.01, < 0.001, < 0.005, 0.03 and 0.01, respectively). Similarly, Bsm-I TT genotype carriers showed significant improvements in triglycerides (p = 0.01), insulin and HOMA-IR (p-values < 0.05). In conclusion, improvements in metabolic profile due to vitamin D supplementation is influenced by VDR polymorphisms, specifically for carriers of Taq-I GG and Bsm-I TT genotypes.
•The potency of vitamin D status correction in reversing MetS has not been addressed on Arab adolescents.•Oral vitamin D supplementation reduces the incidence of MetS in Arab adolescents.•Oral ...vitamin D supplementation is clinically superior to fortified foods in reducing MetS risk factors.
There is little evidence on the efficacy of various vitamin D supplementation strategies in reversing metabolic syndrome (MetS) in adolescents. The present study aims to fill this gap. A total of 535 (243/292) out of 650 apparently healthy Saudi adolescents were randomly selected from the Vitamin D School Project database which has baseline and post-intervention information of more than 1000 Saudi adolescents 12–18 years old attending 34 schools in Riyadh, Saudi Arabia from Nov 2014-May 2015. Allocation of intervention was done in 3 groups using cluster randomization: vitamin D tablet, 1000IU/day (N = 180; 69 boys, 111 girls); vitamin D fortified milk consumption, 200 ml/day, 40IU/100 ml (N = 189; 93 boys, 96 girls) and control (educational awareness) (N = 166; 81 boys, 85 girls). All groups were given educational awareness on how to increase vitamin D levels. All groups were matched for BMI and analysis adjusted for age. Post-intervention and using intent-to-treat approach, within-group analysis revealed a statistically significant increase in 25(OH)D levels in all groups, and a clinically significant increase in favor of the tablet group (between-group) 10.7 nmol/l (34.7%) versus 6.3 nmol/l (19.8%) in milk and 2.1 nmol/l (7.0%) in control; p < 0.001, adjusted for age and BMI-matched. Between group analysis also revealed a clinically significant decrease in triglycerides (p = 0.05), glucose (p < 0.001) and systolic blood pressure (p = 0.005) as well as a clinically significant increase in HDL-cholesterol (p = 0.004) over time, all in favor of the tablet group. Within-group comparison showed a significant decrease in the incidence of MetS in the tablet group (9.4% versus 4.4%; p < 0.05) only. In conclusion, oral vitamin D supplementation is superior to vitamin D fortified milk in improving vitamin D status. Reduction in the incidence of MetS in the Arab adolescent population secondary to vitamin D correction may be dose-dependent.
Spexin (SPX) is a novel peptide thought to have a role in various metabolic regulations. Given its presumed body-weight regulatory functions, we aimed to determine whether lifestyle intervention ...programs on weight loss and fasting glucose (FG) improvement among people with impaired glucose regulation also alter levels of circulating SPX. A total of 160 Saudi adult males and females with prediabetes were randomly selected from a larger cohort (N = 294) who underwent a 6-month lifestyle modification program to improve their glycemic status. Participants were split into two groups based on differences in glucose levels post-intervention, with the first 50% (improved group) having the most significant reduction in FG. SPX was measured at baseline and after 6 months. Changes in SPX was significant only in the improved group baseline: median (Q1-Q3) of 164 pg/ml (136-227) vs follow-up: 176 pg/ml (146-285); p < 0.01. When stratified by sex, the significant increase was observed only in females 159 pg/ml (127-252) vs 182.5 (152,369.1); p < 0.01. Furthermore, SPX levels showed a significant inverse association with FG (β = -0.22, p = 0.003) even after adjustment with age and BMI, again only in females. Circulating SPX levels increase over time in people with prediabetes, particularly women who responded favorably in a 6-month lifestyle intervention program. Whether an unknown mechanism regulating the sexual disparity seen in SPX levels post-intervention exists should be further investigated using a larger sample size.
There are discrepancies in the reports on the association of metabolic syndrome (MetS) and its components with bone mineral density (BMD) and hence more population-based studies on this subject are ...needed. In this context, this observational study was aimed to investigate the association between T-scores of BMD at lumbar L1-L4 and full MetS and its individual components. A total of 1587 participants (84.7% females), >35 years and with risk factors associated with bone loss were recruited from February 2013 to August 2016. BMD was done at L1-L4 using dual-energy X-ray absorptiometry (DXA). T-Scores were calculated. Fasting blood samples and anthropometrics were done at recruitment. Fasting lipid profile and glucose were measured. Screening for full MetS and its components was done according to the National Cholesterol Education Programme Adult Treatment Panel III (NCEP ATP III) criteria. Logistic regression analysis revealed that the odds of having full MetS increased significantly from the lowest T-score tertile to the highest one in both sexes (OR, odd ratio (95% CI, confidence interval) of tertile 2 and 3 at 1.49 (0.8 to 2.8) and 2.46 (1.3 to 4.7),
= 0.02 in males and 1.35 (1.0 to 1.7) and 1.45 (1.1 to1.9),
< 0.01 in females). The odds remained significant even after adjustments with age, body mass index (BMI), and other risk factors associated with bone loss. Among the components of MetS, only central obesity showed a significant positive association with T-score. The study suggests a significant positive association of T-score (spine) with full MetS irrespective of sex, and among the components of MetS this positive association was seen specifically with central obesity.
The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal ...osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1–L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO (OR=1.49, 95% CI 1.0-2.1, P=0.03). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; P=0.048. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO.
Vitamin D supplementation may be used to lower oxidative stress. This interventional study aimed to investigate the effects of vitamin D supplementation on glutathione peroxidase 1 (GPx1) levels and ...other parameters in Arab adults with prediabetes. A total of 203 Saudi adults with prediabetes and vitamin D deficiency intervention group,
= 146 (53 males and 93 females); control group,
= 57 (25 males and 32 females) were included in this non-randomized, six-month intervention study. The intervention group received 50,000 international units (IU) cholecalciferol tablets once a week for two months, then twice a month for the next two months, followed by 1000 IU daily for the last two months. The control group received no supplementation. Serum 25(OH)D, lipid profile, glucose, C-reactive protein (CRP) and GPx1 were measured at baseline and after six months. Post-intervention, GPx1 concentrations increased significantly in the intervention group 17.3 (11.5-59.0) vs 26.7 (11.4-59.9)
< 0.01 while no changes were observed in the control group (
= 0.15). This significant increase in 25(OH)D and GPx1 levels persisted after adjusting for age and BMI. Stratification according to sex revealed that this favourable increase in GPx1 was true only for males (
= 0.002). In all groups, baseline GPx1 was inversely correlated with low density lipoprotein (LDL)-cholesterol (
= -0.26,
< 0.01) and body mass index (BMI) (
= -0.20,
< 0.05), while positively correlated with age (
= 0.18,
< 0.05) and systolic blood pressure (
= 0.19,
< 0.05). In conclusion, vitamin D supplementation favourably enhanced GPx1 levels in adult Arabs with prediabetes, particularly in males.
Osteoporosis and osteopenia has a significant link with substantial fracture risk. Epidemiological data revealed a protective role of adipose tissue on bone biology in postmenopausal osteoporosis. ...The current study assessed the associations between select adipokines and bone mineral density (BMD) in postmenopausal women. A total of 175 Saudi postmenopausal women were selected and categorized based on their BMD (normal & low-BMD). Circulating levels of select adipokines (adiponectin, resistin, leptin, and adipsin), insulin, 25(OH)D and RANKl were determined using commercially available assay kits. BMD was measured by dual-energy X-ray absorptiometry (DXA). Overall and among low-BMD subjects, adiponectin consistently showed a significant inverse association with BMD (overall −0.34, p < 0.01; low BMD group −0.34, p < 0.01). In multiple regression, adiponectin (−0.29 ± 0.06, p < 0.00) and resistin (−0.08 ± 0.04, p < 0.05) were inversely significant with BMD overall, but after stratification the significance was lost for resistin (−0.05 ± 0.04, p < 0.224) whereas adiponectin remained (−0.22 ± 0.07, p < 0.02) in low-BMD subjects. Adipsin, leptin and lipocalin-2 showed no significant associations. Findings of the present study revealed that only adiponectin showed a significantly strong inverse association with low BMD, suggesting that insulin sensitivity may influence bone health in Arab postmenopausal women.
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 T2DM in 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 T2DM patients (0.28 vs 0.45; p<0.0001; OR (95% CI) = 0.4624 (0.3732–0.5729), and therefore the T allele may be a protective factor against T2DM in the Saudi population.
•The effect of vitamin D supplementation in apolipoproteins is limited.•Vitamin modifies apolipoproteins, particularly the apolipoproteins B and C class.•Effects of vitamin D on apolipoproteins are ...sexually dimorphic.
Numerous studies have been done to establish the relationship between vitamin D and lipids, yet a definitive causal link is not found. This interventional study aims to evaluate and compare levels of apolipoproteins among vitamin D deficient subjects at baseline and after they achieved full vitamin D status correction.120 Saudi adults with vitamin D deficiency 25(OH)D < 50nmol/l were recruited and given 50,000IU cholecalciferol weekly for first 2 months, then twice a month for next 2 months, followed by daily 1000IU until month 6. Blood samples were taken at baseline and after 6 months. Serum 25(OH)D, lipid profile and apolipoproteins (A1, A2, B, C1, C2, C3, E and H) were analyzed using commercially available kits. Overall, serum 25(OH)D increased significantly(63.3 ± 16.5nmol/l at end of study vs. 32.5 ± 10.8 at baseline; p < 0.0001). In parallel, a significant increase in apolipoproteins C1, C2, C3 and E (all p-values < 0.01) and a significant decrease in apolipoprotein B (p = 0.02) was observed. Following, stratification according to sex, apolipoproteins C2 and C3 significantly increased only in males (p-values < 0.01) while apolipoprotein C1 significantly increased only in females (p < 0.01). In addition, apolipoprotein B significantly decreased only in females (p = 0.002). These results suggests role of vitamin D in modulation of circulating levels of lipoproteins. The sexual dimorphism observed in circulating levels of measured apolipoproteins following vitamin D correction may explain, in part, known sexual disparity in the events of cardiometabolic health.