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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.  Effect of omega-3 supplementation versus placebo on acylation stimulating protein receptor gene expression in type 2 diabetics 
Background
This randomized controlled trial investigated the role of omega-3 supplementation on C5L2 gene expression in type 2 diabetics.
Methods
Subjects in the omega-3 group received 4 g omega-3 per day and subjects in the placebo group took four capsules of placebo per day for 10 weeks. Gene expression was measured by RT- PCR at the beginning and end of the study.
Results
The results of this study show depletion in the omega-3 group, but the mean difference between two groups was not significant.
Conclusions
Understanding the effect of the omega-3 pathway could contribute to targeting treatment of diabetes and its comorbidities.
doi:10.1186/2251-6581-13-1
PMCID: PMC3937173  PMID: 24393631
Omega-3; Acylation stimulating protein receptor (C5L2); Type 2 diabetes mellitus; Gene expression
3.  Brewer's Yeast Improves Glycemic Indices in Type 2 Diabetes Mellitus 
Background:
Brewer's yeast may have beneficial effects on insulin receptors because of itsglucose tolerance factor in diabetic patients. This study was conducted to investigate the effects of brewer's yeast supplementation on glycemic indices in patients with type 2 diabetes mellitus.
Methods:
In a randomized double-blind controlled clinical trial, 84 adults (21 men and 63 women) aged 46.3 ± 6.1 years old with type 2 diabetes mellitus were recruited and divided randomly into two groups: Supplement group receiving brewer's yeast (six 300mg tablets/day, total 1800 mg) and control group receiving placebo (six 300mg tablets/day) for 12 weeks. Body weight, height, body mass index, food consumption (based on 24h food record), fasting blood sugar (FBS), glycosylated hemoglobin, insulin sensitivity, and insulin resistance were measured before and after the intervention. Data analysis was performed using the Statistical Package for Social Sciences (version 18.0).
Results:
The changes in FBS, glycosylated hemoglobin, and insulin sensitivity were significantly different between the two groups during the study (respectively P < 0.001, P < 0.001, P = 0.02 independent sample t-test). There was a significant difference in FBS, glycosylated hemoglobin, and insulin sensitivity at the end of the study between the two groups after removing the effects of baseline values (respectively P = 0.002, P < 0.001, P = 0.02, analysis of covariance). Changes in body mass index, 24h food record, insulin resistance were not significant.
Conclusions:
Dietary supplementation with brewer›s yeast besides the usual treatment of diabetes can ameliorate blood glucose variables in type 2 diabetes mellitus.
PMCID: PMC3843299  PMID: 24319552
Brewer's yeast; HbA1c; type 2 diabetes
4.  Brewer’s Yeast Improves Blood Pressure in Type 2 Diabetes Mellitus 
Iranian Journal of Public Health  2013;42(6):602-609.
Background
This study was conducted to investigate the effects of Brewer’s yeast supplementation on serum lipoproteins and blood pressure in patients with Type 2 diabetes mellitus.
Methods:
In a randomized double blind clinical trial, 90 adults with type 2 diabetes mellitus were recruited, and divided randomly into 2 groups, trial group received brewer’s yeast (1800 mg/day) and control group received placebo for 12 weeks. Weight, BMI, food consumption (based on 24 hour food recall), fasting serum lipoproteins (Cholesterol, Triglyceride, LDL-c, HDL-c), systolic and diastolic blood pressures were measured before and after the intervention. Data analyses were performed by Statistical Package for Social Sciences ver. 18.0, and the statistical tests included Independent t-test, Paired t-test, Kolmogorov-Smirnov and analysis of covariance. This trial was registered in Iranian Registry of Clinical Trials (IRCT), No.IRCT138807062513N1.
Results:
Eighty-four subjects (21 men and 63 women) aged 46.3±6.1 years completed the study. After 12 weeks supplementation, systolic and diastolic blood pressures were decreased in the group receiving brewer’s yeast (4.1±1.5, P=0.007 and 5.7±0.6, P=0.001 respectively). No-significant changes in LDL-c, HDL-c, Triglyceride and Cholesterol were shown.
Conclusion:
Supplementation with Brewer’s yeast besides the usual treatment of type 2 diabetes mellitus can reduce systolic and diastolic blood pressures in diabetic patients.
PMCID: PMC3744257  PMID: 23967428
Diabetes; Brewer’s yeast; Blood pressure
5.  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
6.  The effect of Omega-3 fatty acids on serum paraoxonase activity, vitamins A, E, and C in type 2 diabetic patients 
BACKGROUND:
Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia. Studies showed paraoxonase activity, and vitamin C and A levels are decreased in diabetes. The effect of omega-3 fatty acids on serum paraoxonase activity and vitamins A, E, C in patients with type 2 diabetes is not fully understood. This study aimed to determine the effect of omega-3 fatty acids on paraoxonase activity, vitamins C, A and E levels in type 2 diabetic patients.
METHODS:
In a double-blind, placebo controlled trial, 80 type 2 diabetic patients were randomly enrolled into the study. Study subjects received daily 2714 mg of omega-3 fatty acids or placebo for 8 weeks. Ten milliliter fasting blood was collected before and after treatments. Serum paraoxonase activity and vitamin C levels were measured by spectrophotometry. Vitamin A and vitamin E were measured using high performance liquid chromatography. Nutrient intake was estimated using 24-hours dietary recall questionnaire (for 2 days) before and after treatments. Dietary data were analyzed using FPII. To compare the means of variables between the two groups, independent t-test was employed. Differences between variables before and after interventions were calculated using paired t-test.
RESULTS:
Serum levels of paraoxonase activity were significantly increased after omega-3 intake (126.47 IU/ml vs. 180.13 IU/ml). However, omega-3 intake caused no significant change in serum vitamin A, C, and E.
CONCLUSIONS:
Supplementation of omega-3 fatty acids was found to increase paraoxonase activity in diabetic patients.
PMCID: PMC3263099  PMID: 22279454
Paraoxonase; Diabetes mellitus; Vitamin C; Vitamin A; Vitamin E
7.  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 1-7 (7)