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1.  Vitamin D Receptor Fok-I Polymorphism Modulates Diabetic Host Response to Vitamin D Intake 
Diabetes Care  2013;36(3):550-556.
OBJECTIVE
Interpopulation as well as interindividual variations in response to vitamin D intake commonly observed in subjects with type 2 diabetes may be related to genetic makeup. One of the candidate genes potentially responsible for this diversity is vitamin D receptor (VDR). This study aimed to investigate the interactive effect of VDR Fok-I polymorphism and vitamin D intake on diverse aspects of diabetic host response.
RESEARCH DESIGN AND METHODS
Glycemic status, lipid profiles, inflammatory biomarkers, and VDR Fok-I genotypes were determined in diabetic subjects (n = 140) who participated in a randomized controlled trial. Participants consumed two 250-mL bottles per day of yogurt drink (doogh) fortified with 500 IU vitamin D/250 mL for 12 weeks.
RESULTS
Mean serum 25(OH)D increased by ~30 nmol/L (P < 0.001). The time × intervention effect was significant for 25(OH)D (P = 0.030), HDL (P = 0.011), high-sensitivity C-reactive protein (hsCRP) (P < 0.001), interleukin (IL)-4 (P = 0.008), and IL-6 (P = 0.017) among the genotypic groups. The alleles were defined as ‘‘F’’ or ‘‘f’’ depending on the absence or presence of the restriction site, respectively. The least increment in 25(OH)D was in ff (23.0 ± 3.8 nmol/L) compared with Ff (31.2 ± 3.4 nmol/L) and FF (35.6 ± 2.7 nmol/L) (P for trend = 0.009), but only the difference between ff and FF was significant (P = 0.023). FF group had the largest decrement of both hsCRP and IL-6 compared with Ff (P < 0.001 and P = 0.038) and ff (P = 0.010 and P = 0.048), respectively.
CONCLUSIONS
We concluded that those of VDR ff genotype may be regarded as “low responders” to vitamin D intake in terms of response of circulating 25(OH)D and certain inflammatory biomarkers. A nutrigenetic approach may, therefore, be needed to protect diabetic patients from vitamin D deficiency.
doi:10.2337/dc12-0919
PMCID: PMC3579338  PMID: 23160722
2.  Regular consumption of vitamin D-fortified yogurt drink (Doogh) improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial 
BMC Medicine  2011;9:125.
Background
Endothelial dysfunction has been proposed as the underlying cause of diabetic angiopathy that eventually leads to cardiovascular disease, the major cause of death in diabetes. We recently demonstrated the ameliorating effect of regular vitamin D intake on the glycemic status of patients with type 2 diabetes (T2D). In this study, the effects of improvement of vitamin D status on glycemic status, lipid profile and endothelial biomarkers in T2D subjects were investigated.
Methods
Subjects with T2D were randomly allocated to one of the two groups to receive either plain yogurt drink (PYD; containing 170 mg calcium and no vitamin D/250 mL, n1 = 50) or vitamin D3-fortified yogurt drink (FYD; containing 170 mg calcium and 500 IU/250 mL, n2 = 50) twice a day for 12 weeks. Anthropometric measures, glycemic status, lipid profile, body fat mass (FM) and endothelial biomarkers including serum endothelin-1, E-selectin and matrix metalloproteinase (MMP)-9 were evaluated at the beginning and after the 12-week intervention period.
Results
The intervention resulted in a significant improvement in fasting glucose, the Quantitative Insulin Check Index (QUICKI), glycated hemoglobin (HbA1c), triacylglycerols, high-density lipoprotein cholesterol (HDL-C), endothelin-1, E-selectin and MMP-9 in FYD compared to PYD (P < 0.05, for all). Interestingly, difference in changes of endothelin-1, E-selectin and MMP-9 concentrations in FYD compared to PYD (-0.35 ± 0.63 versus -0.03 ± 0.55, P = 0.028; -3.8 ± 7.3 versus 0.95 ± 8.3, P = 0.003 and -2.3 ± 3.7 versus 0.44 ± 7.1 ng/mL, respectively, P < 0.05 for all), even after controlling for changes of QUICKI, FM and waist circumference, remained significant for endothelin-1 and MMP-9 (P = 0.009 and P = 0.005, respectively) but disappeared for E-selectin (P = 0.092). On the contrary, after controlling for serum 25(OH)D, the differences disappeared for endothelin-1(P = 0.066) and MMP-9 (P = 0.277) but still remained significant for E-selectin (P = 0.011).
Conclusions
Ameliorated vitamin D status was accompanied by improved glycemic status, lipid profile and endothelial biomarkers in T2D subjects. Our findings suggest both direct and indirect ameliorating effects of vitamin D on the endothelial biomarkers.
Trial registration
ClinicalTrials.gov: NCT01236846
doi:10.1186/1741-7015-9-125
PMCID: PMC3239240  PMID: 22114787
3.  Efficacy of vitamin D3-fortified-yogurt drink on anthropometric, metabolic, inflammatory and oxidative stress biomarkers according to vitamin D receptor gene polymorphisms in type 2 diabetic patients: a study protocol for a randomized controlled clinical trial 
Background
Development of type 2 diabetes mellitus (T2DM) is determined by the interactions of genetic and environmental factors. This study was designed to evaluate the possible role of VDR single nucleotide polymorphisms (SNPs) on different aspects of diabetic host response (anthropometric, metabolic, oxidative stress and inflammatory) to daily intake of vitamin D through fortified yogurt drink for 12 weeks.
Methods/Design
This study comprises two parts: (i) a case-control study; and (ii) an intervention trial. In the first part, VDR polymorphisms (Taq1, FokI, Apa1, Bsm1, and Cdx2) are determined in 350 T2DM patients and 350 non-diabetic subjects. In the second part, the possible effects of daily intake of two servings of vitamin D3-fortified yogurt drink (FYD; 500 IU vitamin D/250 mL) on some selected metabolic (including insulin resistance), inflammatory and oxidative stress biomarkers in 135 T2DM patients are assessed. To relate the resulted changes in the biomarkers to vitamin D replenishment, another group of diabetic patients (n = 45) are also included in the study who receive 2 servings of plain yogurt drink (PYD) a day. The primary outcome is serum level of 25(OH) D, which it is expected to be elevated only in FYD group. Secondary outcomes include improvements in glycemic, metabolic, inflammatory and oxidative stress biomarkers in FYD group compared to PYD group. Three VDR FokI polymorphisms are determined only in FYD group followed by comparison of changes in the biomarkers among these genotypic variants.
Discussion
The present study, at least in part, elucidates the discrepancies in the results of different vitamin D-diabetes studies pertaining to the genetic variations of the population. If VDR polymorphisms are found to influence the response to our intervention, then knowing distribution of VDR polymorphisms in both diabetic and non-diabetic populations can give a picture of the proportion of the community in whom up to 1000 IU/d vitamin D may not be effective enough to improve insulin resistance and related morbidities. Therefore, they should ideally receive further nutritional support according to their genotype.
Trial Registration
ClinicalTrials.gov: NCT01236846
doi:10.1186/1472-6823-11-12
PMCID: PMC3146888  PMID: 21696575
vitamin D; vitamin D receptor; polymorphism; type 2 diabetes; study protocol

Results 1-3 (3)