Improvement of NRF2 gene expression and antioxidant status in patients with type 2 diabetes mellitus after supplementation with omega-3 polyunsaturated fatty acids: A double-blind randomised placebo-controlled clinical trial.

BACKGROUND: Nrf2 is a transcription factor that induces the expression of several proteins with antioxidant properties such as sestrin2 (Sesn2) and is therefore considered as the major regulator of anti-oxidative defence system. OBJECTIVES: The aim of this research was to study the effect of supplementation with n-3 PUFAs on the antioxidant status and the gene expression of Nrf2 and Sestrin2 (Sesn2) in patients with type 2 diabetes mellitus (T2DM). PARTICIPANTS: Sixty patients with T2DM were enrolled in a placebo-controlled, double-blind, randomised clinical trial. INTERVENTION AND DESIGN: The participants were randomly allocated to two intervention groups receiving either n-3 PUFAs (2,700 mg/day) (n = 30) or placebo soft gels containing 900 mg of edible paraffin (n = 30). The main outcome measures were the expression of Sesn2 and Nrf2 genes which were assessed in peripheral blood mononuclear cells (PBMCs) after RNA extraction and cDNA synthesis by real-time PCR. Total antioxidant status in plasma samples was also measured based on the ferric reducing ability of plasma. RESULTS: NRF2 gene expression was significantly increased in n-3 PUFA-supplemented subjects, compared with the placebo group. Plasma total antioxidant status was also significantly augmented in n-3 PUFA-supplemented subjects. SESN2 gene expression was not significantly affected by n-3 PUFA supplementation although a slight up-regulation was observed. CONCLUSION: Supplementation with n-3 PUFAs enhanced NRF2 gene expression and improved overall antioxidant capacity and thus might be considered beneficial in the amelioration of oxidative stress and prevention of T2DM complications. TRIAL REGISTRATION: IRCT20150926024198N4.

Long Chain n-3 Fatty Acids Improve Depression Syndrome in Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is commonly associated with depressive symptoms, which affect prognosis and quality of life. We investigated the antidepressant effects of n-3 fatty acids (n-3FAs) monotherapy (without conventional antidepressants) for T2DM patients with mild to moderate depressive symptoms. METHODS: A 10-wk, placebo-controlled, double-blind, parallel-group (1:1 ratio) randomized trial of n-3FAs (2700 mg/day EPA: DHA ratio=2) versus placebo in 88 Iranian diabetic patients with mild to moderate depression based on Beck Depression Inventory II (BDI-II-PERSIAN) was conducted. This study started from July 2014 to January 2015 in Tehran University of Medical Sciences, Tehran, Iran. The primary event was defined as worsened, non-changed, or inconsiderably improved depression (<5 unit decrease in BDI-II-PERSIAN depression scores after treatment) (ClinicalTrials.gov Identifier: NCT02261545). RESULTS: Randomly, 44 T2DM patients were treated with n-3FAs supplements and 44 cases received placebo (three patients discontinued). n-3FAs could significantly protect patients against the aforesaid event and exhibit satisfactory prevention (number needed to treat with 95% confidence interval: 2.52, 1.71-4.74). No serious adverse reactions were reported. CONCLUSION: n-3FAs supplementation had significant antidepressant effects in T2DM patients with mild to moderate depressive symptoms, not confounded by metabolic factors and disease duration.

Beneficial Effects of n-3 Fatty Acids on Cardiometabolic and Inflammatory Markers in Type 2 Diabetes Mellitus: A Clinical Trial.

OBJECTIVE: To determine the effect of supplementation with n-3 polyunsaturated fatty acids (PUFAs) on circulatory resistin and monocyte chemoattractant protein 1 (MCP-1) levels in type 2 diabetes mellitus (T2DM) patients. SUBJECTS AND METHODS: This was a 10-week, placebo-controlled, double-blind, randomized trial of n-3 PUFAs (2,700 mg/day) versus placebo (soft gels containing 900 mg of edible paraffin). Forty-four T2DM patients were supplemented with n-3 PUFAs and another 44 patients received placebo (3 patients discontinued the trial). Serum resistin, MCP-1, and the lipid profile were measured before and after supplementation. The adiponectin-resistin index (1 + log10 [resistin] - log10 [adiponectin]) and atherogenic index (log10 triglyceride/high-density lipoprotein cholesterol) of plasma (an indicator of cardiovascular complications) were assessed. The independent Student t test was used to assess the differences between the supplement and placebo groups and the paired t test to analyze the before/after changes. RESULTS: In this study, n-3 PUFAs reduced serum MCP-1 levels (from 260.5 to 230.5 pg/mL; p = 0.002), but they remained unchanged in the placebo group. n-3 PUFAs could not decrease serum resistin levels. The adiponectin-resistin index was significantly reduced after supplementation with n-3 PUFAs when compared to the placebo. The atherogenic index was also significantly improved after supplementation with n-3 PUFAs (from 1.459 to 1.412; p = 0.006). CONCLUSIONS: The MCP-1 levels and lipid profile were improved after supplementation with n-3 PUFAs, but resistin serum levels were not changed. Hence, the anti-inflammatory effects of n-3 PUFAs might be mediated by targeting MCP-1.

The Effect of n-3 Polyunsaturated Fatty Acids Supplementation on Serum Irisin in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Diabetes refers to a group of metabolic diseases with blood glucose of higher than normal ranges. Furthermore, n-3 polyunsaturated fatty acids are necessary for the regulation of the activity of human function. The effect of n-3 PUFA on diabetes has been investigated in animal studies, yet, the exact amount has not been set, to date. Irisin, as a new myokine, is released from skeletal muscle and Irisin levels decrease as a result of physical inactivity, overweightness, and obesity. Also, the reduction of serum irisin level is associated with development of insulin resistance and type 2 diabetes. This study was performed to assess the effects of n-3 PUFA supplementation on serum irisin level in patients with diabetes. METHODS: This randomized clinical trial included 43 patients with type 2 diabetes (21 patients in the placebo group and 22 patients in the n-3 PUFA supplement group). They were randomized to groups, one receiving 10 weeks of either n-3 PUFA supplement and the other the placebo (1250 mg capsule, three times per day). Samples were also matched by age, gender, and body mass index (BMI) in the 2 groups. Anthropometric measurements, demographic information and dietary intakes were obtained both before and after the intervention. Serum irisin levels were measured before and after the intervention using human irisin enzyme linked immunosorbent assay (ELISA) kit. Independent t-test was used to compare the mean outcomes between groups. RESULTS: At baseline, irisin serum levels were not significantly different between the placebo and n-3 PUFA supplementation groups (P > 0.05). However, a significant change was observed between the groups after intervention (P = 0.04). Also there was a significant difference in mean change (after versus before the intervention) (P = 0.05). Compared to the placebo, n-3 PUFA supplementation decreased serum FBS and HbA1C (P = 0.036 and 0.001; respectively). Also, there were significant differences between changes of diastolic blood pressure and HOMA-IR after the intervention between the groups. The duration of illness was not considered as a confounding factor because there was no significant association between irisin level (after versus before the intervention) and the illness duration. CONCLUSIONS: The current study indicated that n-3 PUFA supplementation with a dosage of 1250 mg three times per day, resulted in increased serum irisin level of diabetic patients.

Beneficial effects of n-3 polyunsaturated fatty acids on adiponectin levels and AdipoR gene expression in patients with type 2 diabetes mellitus: a randomized, placebo-controlled, double-blind clinical trial.

INTRODUCTION: There is evidence that n-3 polyunsaturated fatty acids (n-3 PUFAs) exert beneficial effects to improve type 2 diabetes mellitus (T2DM), but its complications remain poorly understood. Hypoadiponectinemia is one of the important mechanisms responsible for T2DM which necessitates developing novel therapeutic strategies. We aimed to determine the effect of n-3 PUFA supplementation on circulating adiponectin and mRNA expression of adiponectin receptors (AdipoR1, AdipoR2) and Sirt-1 in T2DM patients. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled trial of 10-week follow-up of n-3 PUFAs (2.7 g/day) vs. placebo in T2DM patients (n = 88) was conducted. In detail, T2DM patients (n = 44) were treated with n-3 PUFAs and the remainder received placebo. Anthropometric and metabolic characteristics were assessed in all participants. Circulating level of adiponectin and mRNA expression of AdipoR1, AdipoR2 and Sirt-1 were measured in peripheral blood mononuclear cells (PBMC) using real-time polymerase chain reaction before and after the intervention. RESULTS: It was found that n-3 PUFAs increased AdipoR1 gene expression (fold change = 1.321 in n-3 PUFAs vs. 1.037 in placebo) and AdipoR2 mRNA (fold change = 1.338 in n-3 PUFAs vs. 1.034 in placebo). No significant changes were observed for Sirt-1 expression. The serum level of adiponectin significantly (p = 0.035) increased in n-3 PUFAs (5.09 to 5.58 µg/ml) but remained unchanged in the placebo group. CONCLUSIONS: Daily supplementation with n-3 PUFAs (2.7 g) was effective to significantly improve gene expression of AdipoR1 and AdipoR2 and the serum level of adiponectin in T2DM patients. Therefore, n-3 PUFAs might emerge as an adjuvant for current antidiabetic therapies. However, confirmatory long-term studies are required.

Portal and systemic levels of visfatin in morbidly obese subjects undergoing bariatric surgery.

The aim of the present study was to compare the levels of visfatin in portal and systemic circulations and to assess the possible relationship of visfatin with systemic inflammation and insulin resistance in morbidly obese patients undergoing bariatric surgery. A total of 46 morbidly obese patients (BMI = 45.3 ± 5.3 kg/m(2)) undergoing bariatric surgery were included in this study. Blood samplings were performed simultaneously from portal and systemic veins during surgery. Visfatin was measured in both portal and systemic venous samples. Besides, fasting serum levels of insulin, glucose, lipid profile, visfatin, and hs-CRP were determined in systemic venous blood samples. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). Visfatin concentrations were significantly higher in portal vein than systemic veins (11.9 ± 12.1 vs. 5.1 ± 3.3 ng/ml, p < 0.0001). While systemic levels of visfatin were significantly correlated with circulating levels of hs-CRP (r = 0.527, p < 0.0001), there were no significant correlations between portal levels of visfatin with systemic levels of hs-CRP concentrations. Substantially higher levels of visfatin in portal vein than systemic veins provide evidence that visceral adipose tissue is the major secretory source of visfatin in humans. Our findings underscore that visceral adipose tissue is an active endocrine organ that is involved in the complex interrelationship between obesity and pathologic conditions.

Elevated serum visfatin levels in patients with acute myocardial infarction.

BACKGROUND: Visfatin, a novel adiopocytokine, has been proven to be a proinflammatory mediator involved in the process of atherosclerosis. Visfatin has been shown to play a role in plaque destabilization as it is found abundantly in foam cell macrophages within unstable atherosclerotic plaques. The present study is designed to investigate the potential association between serum vistafin levels and the risk of acute myocardial infarction (AMI).  METHODS: There were 72 patients (mean age: 61.57 ± 11.40 years) as cases who presented with first-time AMI that were assessed 8 hours after the incident. The control group consisted of 83 healthy volunteers (mean age: 60.30 ± 8.32 years). Plasma visfatin levels were measured using enzyme immunoassay in both groups. Biochemical parameters were analyzed. Blood pressure, body mass index (BMI), waist circumference, diabetes, and hypertension were recorded.  RESULTS: Serum visfatin levels were significantly higher in patients with AMI (12.77 ± 8.06 ng/ml) compared to controls (6.57 ± 2.96 ng/ml, P ≤ 0.001). We found that a visfatin level > 7.244 ng/ml (log visfatin > 0.86) had a sensitivity of 70% and a specificity of 75% for predicting AMI.  CONCLUSION: We have detected high levels of visfatin in patients with AMI. It can be concluded that proinflammatory cytokines such as visfatin may play a role in the development of atherosclerosis as well as destabilization of the atherosclerotic plaque.

Serum visfatin concentrations in gestational diabetes mellitus and normal pregnancy.

PURPOSE: There is conflicting data regarding visfatin in gestational diabetes mellitus (GDM). The aim of the present study was to compare serum visfatin levels between patients with GDM and subjects with normal pregnancy and to evaluate its relationship with dietary intake and components of insulin-resistance syndrome. METHODS: Thirty-five patients with GDM (aged 31 ± 0.8 years, BMI = 29.6) and 35 age- and body mass index-matched healthy pregnant women (aged 29 ± 0.7 years, BMI = 28.6) between 24 and 28 weeks of gestation were studied. In addition to anthropometric and dietary intake assessments, measurements of fasting plasma levels of visfatin, glucose, insulin, hemoglobin A1c (HbA1c) and lipid profile were performed for all subjects. RESULTS: Plasma visfatin levels were significantly lower in pregnant women with GDM compared to healthy subjects (5.29 ± 0.47 vs. 7.76 ± 0.53, p = 0.001). After adjustment for age, maternal gestational age, body mass index, and macronutrients intake, GDM remained the independent predictor of serum visfatin concentrations (ß = -1.2, p = 0.001). Serum visfatin levels were significantly correlated with log HbA1c values (r = -0.24, p = 0.03), even after adjustment for age and body mass index (ß = -6.45, p = 0.05). No associations between visfatin and other parameters of the insulin-resistance syndrome as well as macronutrient intake were detectable. CONCLUSIONS: Plasma visfatin concentrations are lower in patients with GDM and related to glycemic control reflected by HbA1c. Furthermore, visfatin does not seem to be correlated with dietary intake in pregnant women.