Associations of Type 2 Diabetes with Common Variants in PPARD and the Modifying Effect of Vitamin D among Middle-Aged and Elderly Chinese

BACKGROUND: Previous studies have identified that variants in peroxisome proliferator-activated receptor PPAR-δ (PPARD), a target gene of vitamin D, were significantly associated with fasting glucose and insulin sensitivity in European populations. This current study sought to determine (1) whether the genetic associations of PPARD variants with type 2 diabetes and its related traits could be replicated in Chinese Han population, and (2) whether the associations would be modified by the effect of vitamin D status. METHODS AND FINDINGS: We genotyped 9 tag single nucleotide polymorphisms (SNPs) that cover the gene of PPARD (rs2267664, rs6902123, rs3798343, rs2267665, rs2267668, rs2016520, rs2299869, rs1053049, and rs9658056) and tested their associations with type 2 diabetes risk and its related traits, including fasting glucose, insulin and HbA1c in 3,210 Chinese Hans. Among the 9 PPARD tag SNPs, rs6902123 was significantly associated with risk of type 2 diabetes (odds ratio 1.75 [95%CI 1.22-2.53]; P = 0.0025) and combined type 2 diabetes and impaired fasting glucose (IFG) (odds ratio 1.47 [95%CI 1.12-1.92]; P = 0.0054). The minor C allele of rs6902123 was associated with increased levels of fasting glucose (P = 0.0316) and HbA1c (P = 0.0180). In addition, we observed that vitamin D modified the effect of rs6902123 on HbA1c (P for interaction = 0.0347). CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that common variants in PPARD contribute to the risk of type 2 diabetes in Chinese Hans, and provided suggestive evidence of interaction between 25(OH)D levels and PPARD-rs6902123 on HbA1c

Effects of vitamin D supplementation on endothelial function:a systematic review and meta-analysis of randomised clinical trials

Background: In addition to regulating calcium homoeostasis and bone health, vitamin D influences vascular and metabolic processes including endothelial function (EF) and insulin signalling. This systematic review and meta-analysis of randomised clinical trials (RCTs) were conducted to investigate the effect of vitamin D supplementation on EF and to examine whether the effect size was modified by health status, study duration, dose, route of vitamin D administration, vitamin D status (baseline and post-intervention), body mass index (BMI), age and type of vitamin D.  Methods: We searched the Medline, Embase, Cochrane Library and Scopus databases from inception until March 2015 for studies meeting the following criteria: (1) RCT with adult participants, (2) vitamin D administration alone, (3) studies that quantified EF using commonly applied methods including ultrasound, plethysmography, applanation tonometry and laser Doppler.  Results: Sixteen articles reporting data for 1177 participants were included. Study duration ranged from 4 to 52 weeks. The effect of vitamin D on EF was not significant (SMD: 0.08, 95 % CI −0.06, 0.22, p = 0.28). Subgroup analysis showed a significant improvement of EF in diabetic subjects (SMD: 0.31, 95 % CI 0.05, 0.57, p = 0.02). A non-significant trend was found for diastolic blood pressure (β = 0.02; p = 0.07) and BMI (β = 0.05; p = 0.06).  Conclusions: Vitamin D supplementation did not improve EF. The significant effect of vitamin D in diabetics and a tendency for an association with BMI may indicate a role of excess adiposity and insulin resistance in modulating the effects of vitamin D on vascular function. This remains to be tested in future studies

Vitamin D Receptor Gene Polymorphisms Modify Cardiometabolic Response to Vitamin D Supplementation in T2DM Patients

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

25-Hydroxyvitamin D and pre-clinical alterations in inflammatory and hemostatic markers: a cross sectional analysis in the 1958 British Birth Cohort

BACKGROUND: Vitamin D deficiency has been suggested as a cardiovascular risk factor, but little is known about underlying mechanisms or associations with inflammatory or hemostatic markers. Our aim was to investigate the association between 25-hydroxyvitamin D [25(OH)D, a measure for vitamin D status] concentrations with pre-clinical variations in markers of inflammation and hemostasis. METHODOLOGY/PRINCIPAL FINDINGS: Serum concentrations of 25(OH)D, C-reactive protein (CRP), fibrinogen, D-dimer, tissue plasminogen activator (tPA) antigen, and von Willebrand factor (vWF) were measured in a large population based study of British whites (aged 45 y). Participants for the current investigation were restricted to individuals free of drug treated cardiovascular disease (n = 6538). Adjusted for sex and month, 25(OH)D was inversely associated with all outcomes (p or =75 nmol/l compared to < 25 nmol/l. D-dimer concentrations were lower for participants with 25(OH)D 50-90 nmol/l compared to others (quadratic term p = 0.01). We also examined seasonal variation in hemostatic and inflammatory markers, and evaluated 25(OH)D contribution to the observed patterns using mediation models. TPA concentrations varied by season (p = 0.02), and much of this pattern was related to fluctuations in 25(OH)D concentrations (p < or =0.001). Some evidence of a seasonal variation was observed also for fibrinogen, D-dimer and vWF (p < 0.05 for all), with 25(OH)D mediating some of the pattern for fibrinogen and D-dimer, but not vWF. CONCLUSIONS: Current vitamin D status was associated with tPA concentrations, and to a lesser degree with fibrinogen and D-dimer, suggesting that vitamin D status/intake may be important for maintaining antithrombotic homeostasi

Maternal Plasma 25-Hydroxyvitamin D Concentrations and the Risk for Gestational Diabetes Mellitus

Background: Evidence is accumulating for a role of vitamin D in maintaining normal glucose homeostasis. However, studies that prospectively examined circulating concentrations of 25-hydroxyvitamin D (25-[OH] D) in relation to diabetes risk are limited. Our objective is to determine the association between maternal plasma 25-[OH] D concentrations in early pregnancy and the risk for gestational diabetes mellitus (GDM). Methods: A nested case-control study was conducted among a prospective cohort of 953 pregnant women. Among them, 57 incident GDM cases were ascertained and 114 women who were not diagnosed with GDM were selected as controls. Controls were frequency matched to cases for the estimated season of conception of the index pregnancy. Results: Among women who developed GDM, maternal plasma 25-[OH] D concentrations at an average of 16 weeks of gestation were significantly lower than controls (24.2 vs. 30.1 ng/ml, P<0.001). This difference remained significant (3.62 ng/ml lower on average in GDM cases than controls (P value = 0.018)) after the adjustment for maternal age, race, family history of diabetes, and pre-pregnancy BMI. Approximately 33% of GDM cases, compared with 14% of controls (P<0.001), had maternal plasma 25-[OH] D concentrations consistent with a pre-specified diagnosis of vitamin D deficiency (<20 ng/ml). After adjustment for the aforementioned covariates including BMI, vitamin D deficiency was associated with a 2.66-fold (OR (95% CI): 2.66 (1.01–7.02)) increased GDM risk. Moreover, each 5 ng/ml decrease in 25-[OH] D concentrations was related to a 1.29-fold increase in GDM risk (OR (95% CI): 1.29 (1.05–1.60)). Additional adjustment for season and physical activity did not change findings substantially. Conclusions: Findings from the present study suggest that maternal vitamin D deficiency in early pregnancy is significantly associated with an elevated risk for GDM

The effects of progressive resistance training combined with a whey-protein drink and vitamin D supplementation on glycaemic control, body composition and cardiometabolic risk factors in older adults with type 2 diabetes: study protocol for a randomized controlled trial

Background - While physical activity, energy restriction and weight loss are the cornerstone of type 2 diabetes management, less emphasis is placed on optimizing skeletal muscle mass. As muscle is the largest mass of insulin-sensitive tissue and the predominant reservoir for glucose disposal, there is a need to develop safe and effective evidence-based, lifestyle management strategies that optimize muscle mass as well as improve glycaemic control and cardiometabolic risk factors in people with this disease, particularly older adults who experience accelerated muscle loss. Methods/Design - Using a two-arm randomized controlled trial, this 6-month study builds upon the community-based progressive resistance training (PRT) programme Lift for Life® to evaluate whether ingestion of a whey-protein drink combined with vitamin D supplementation can enhance the effects of PRT on glycaemic control, body composition and cardiometabolic health in older adults with type 2 diabetes. Approximately 200 adults aged 50 to 75 years with type 2 diabetes, treated with either diet alone or oral hypoglycaemic agents (not insulin), will be recruited. All participants will be asked to participate in a structured, supervised PRT programme based on the Lift for Life® programme structure, and randomly allocated to receive a whey-protein drink (20 g daily of whey-protein plus 20 g after each PRT session) plus vitamin D supplements (2000 IU/day), or no additional powder and supplements. The primary outcome measures to be collected at baseline, 3 and 6 months will be glycated haemoglobin (HbA1c) and insulin sensitivity (homeostatic model assessment). Secondary outcomes will include changes in: muscle mass, size and intramuscular fat; fat mass; muscle strength and function; blood pressure; levels of lipids, adipokines and inflammatory markers, serum insulin-like growth factor-1 and 25-hydroxyvitamin D; renal function; diabetes medication; health-related quality of life, and cognitive function. Discussion - The findings from this study will provide new evidence on whether increased dietary protein achieved through the ingestion of a whey-protein drink combined with vitamin D supplementation can enhance the effects of PRT on glycaemic control, muscle mass and size, and cardiometabolic risk factors in older adults with type 2 diabetes