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1.  The effect of omega-3 on the serum visfatin concentration in patients with type II diabetes 
BACKGROUND:
Visfatin is an adipocytokine which is secreted from adipose tissue and can affect on the diabetes inflammatory reaction and also serum lipids level. On the other hand, Omega-3 can also prevent formation of insulin resistance. In the present study, the effect of Omega-3 on the serum visfatin concentration was evaluated.
METHODS:
71 women with type II diabetes were randomly assigned to the group that took Omega-3 capsules or control group with placebo capsules. In the first step, study subjects filled a questionnaire collecting their age, height, weight, waist circumference, and hip circumference. Also their blood samples were taken for blood tests. In the second step, the intervention was done for 8 weeks and in the third step the aforementioned were collected again. In the blood samples visfatin and lipid profiles (low density lipoprotein [LDL], high density lipoprotein [HDL], triglyceride [TG], and cholesterol), glucose and HbA1c were measured.
RESULTS:
There was no significant difference in serum visfatin level between Omega-3 and placebo groups before the intervention (p = 0.14), while after the intervention, the mean serum visfatin level in the Omega-3 group was significantly higher (p < 0.001). In addition, the mean difference between the serum visfatin level before and after the intervention in both groups was significant (p < 0.001).
CONCLUSIONS:
This study showed an increase in visfatin level following consuming Omega-3 fats but according to controversial issues on insulin-like function of visfatin, the effects of Omega-3 on diabetes should be studied more in further studies.
PMCID: PMC3214353  PMID: 22091264
Fatty Acids; Omega-3; Nicotinamide Phosphoribosyltransferase; Diabetes Mellitus; Type 2
2.  The Effect of Omega-3 Supplements on Antioxidant Capacity in Patients with Type 2 Diabetes 
International Journal of Preventive Medicine  2013;4(Suppl 2):S234-S238.
Background:
Diabetes is one of the most common chronic diseases in which antioxidant capacity changes. Omega-3 fatty acids have extensive biological effects including their advantage on lipoprotein metabolism, platelet function, cytokine production, clotting, fibrinolysis, and inflammatory factors. This study aimed to investigate the effect of omega-3 fatty acid supplements on antioxidant capacity in patients with type 2 diabetes.
Methods:
This clinical trial enrolled 71 women with type 2 diabetes in two case (treated with omega-3 capsules) and control (treated with placebo) groups. In the first stage, participants filled out a demographics questionnaire including age, height, weight, waist circumference, and hip circumference.Their blood sample was taken to evaluate glycosylated hemoglobin and antioxidant capacity. Then the case group received intervention for 8 weeks and weight, waist circumference, and hip circumference were measured and a blood sample was taken again. The data were analyzed using SPSS 18 software.
Results:
The mean difference of antioxidant capacity before and after intervention was significant (P < 0.001). Antioxidant capacity increased in the case group and reduced in the control group.
Conclusions:
With regard to the results of the present study, patients with type 2 diabetes increase their antioxidant capacity, enhance their antioxidant defense system, and probably prevent diabetes complications and related disease progress by taking omega-3 supplements.
PMCID: PMC3678224  PMID: 23776730
Antioxidant capacity; omega-3 supplement; type 2 diabetes
3.  Circulating visfatin level and visfatin/insulin ratio in obese women with metabolic syndrome 
Introduction
Visfatin is an adipokine secreted by visceral adipose tissue with insulin-mimetic properties. Higher circulating visfatin levels were reported in type 2 diabetes. The aim of this study was to analyse circulating visfatin and insulin levels and the visfatin/insulin ratio in obese women with and without metabolic syndrome (MetS).
Material and methods
The study involved 92 obese women. Subjects were diagnosed with MetS according to IDF 2005 criteria. The MetS group consisted of 71 subjects (age: 52.8 ±9.4 years, body mass index [BMI]: 39.1 ±5.6 kg/m2, waist circumference: 109.6 ±11.4 cm and fat mass: 52.0 ±12.8 kg) while the non-MetS group consisted of 21 subjects (age: 51.7 ±9.5 years, BMI: 36.3 ±5.2 kg/m2, waist circumference: 104.7 ±11.0 cm and fat mass: 45.2 ±10.7 kg). In addition to anthropometric measurements and assessment of serum glucose and lipids, plasma concentrations of visfatin were estimated by enzyme-linked immunosorbent assay (ELISA) and of insulin by radioimmunoassay (RIA). Homeostatic model assessment insulin resistance (HOMA-IR) and visfatin/insulin ratio were calculated.
Results
In the MetS group significantly higher (p < 0.01) plasma concentrations of insulin and HOMA-IR values but similar visfatin levels were observed than in the non-MetS group. As a consequence of the significantly higher plasma insulin concentration the visfatin/insulin ratio was significantly lower in the MetS group (p < 0.05). The visfatin/insulin ratio correlated inversely with anthropometric parameters such as body mass, BMI, body fat and waist circumference (r = –0.41, p = 0.0003; r = –0.42, p = 0.0002; r = –0.29, p = 0.01; r = –0.23, p = 0.04, respectively).
Conclusions
We conclude that the visfatin/insulin ratio declining with increasing visceral obesity may predispose to the development of insulin resistance.
doi:10.5114/aoms.2012.28547
PMCID: PMC3361032  PMID: 22661992
visfatin; insulin; obesity; metabolic syndrome
4.  Relationship between adipocytokines and cardiovascular risk factors in patients with type 2 diabetes mellitus 
The aim of this study was to explore the relationship between serum profiles of adiponectin, leptin, resistin and visfatin and traditional and non-traditional cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). A total of 85 patients with T2DM and 30 non-diabetic controls were enrolled in the study. Levels of adipocytokines (adiponectin, leptin, resistin and visfatin), lipids (total cholesterol, triglycerides), lipoproteins [HDL-cholesterol, LDL-cholesterol, lipoprotein (a)], apolipoproteins (Apo-A1 and Apo-B), non-traditional cardiovascular risk markers [asymmetric dimethylarginine (ADMA), homocysteine] and the inflammatory marker hs-CRP were measured, and anthropometric variables were determined. Serum adiponectin levels were decreased and leptin, resistin and visfatin levels were increased in T2DM patients compared to controls. They were associated with obesity (BMI), insulin resistance (HOMA-IR) and various markers of glucose/lipid profile, inflammation and endothelial dysfunction markers. These results suggest that decreased serum adiponectin and increased leptin, resistin and visfatin levels in T2DM may be novel biochemical risk factors for cardiovascular complications.
doi:10.3892/etm.2012.557
PMCID: PMC3460256  PMID: 23060933
adipocytokines; cardiovascular risk markers; type 2 diabetes mellitus
5.  Visceral Adiposity Index (VAI) Is Predictive of an Altered Adipokine Profile in Patients with Type 2 Diabetes 
PLoS ONE  2014;9(3):e91969.
Aims
Although there is still no clear definition of “adipose tissue dysfunction” or ATD, the identification of a clinical marker of altered fat distribution and function may provide the needed tools for early identification of a condition of cardiometabolic risk. Our aim was to evaluate the correlations among various anthropometric indices [BMI, Waist Circumference (WC), Hip Circumference (HC), Waist/Hip ratio (WHR), Body Adiposity Index (BAI) and Visceral adiposity Index (VAI)] and several adipocytokines [Visfatin, Resistin, Leptin, Soluble leptin receptors (sOB-R), Adiponectin, Ghrelin, Adipsin, PAI-1, vascular endothelial growth factor (VEGF), Hepatocyte growth factor (HGF) TNF-α, hs-CRP, IL-6, IL-18] in patients with type 2 diabetes (DM2).
Materials and Methods
Ninety-one DM2 patients (age: 65.25±6.38 years; 42 men and 49 women) in stable treatment for the last six months with metformin in monotherapy (1.5–2 g/day) were cross-sectionally studied. Clinical, anthropometric, and metabolic parameters were evaluated. Serum adipocytokine levels were assayed with Luminex based kits.
Results
At the Pearson’s correlation, among all the indices investigated, VAI showed a significant correlation with almost all adipocytokines analyzed [Visfatin, Resistin and hsCRP (all p<0.001); Adiponectin, sOb-R, IL-6, IL-18, HGF (all p<0.010); Ghrelin and VEGF (both p<0.05)]. Through a two-step cluster analysis, 55 patients were identified with the most altered adipocytokine profile (patients with ATD). At a ROC analysis, VAI showed the highest C-statistic [0.767 (95% CI 0.66–0.84)] of all the indices.
Conclusions
Our study suggests that the VAI, among the most common indexes of adiposity assessment, shows the best correlation with the best known adipocytokines and cardiometabolic risk serum markers. Although to date we are still far from clearly identifying an ATD, the VAI would be an easy tool for clearly mirroring a condition of cardiometabolic risk, in the absence of an overt metabolic syndrome.
doi:10.1371/journal.pone.0091969
PMCID: PMC3961281  PMID: 24651545
6.  Visfatin Is Regulated by Rosiglitazone in Type 2 Diabetes Mellitus and Influenced by NFκB and JNK in Human Abdominal Subcutaneous Adipocytes 
PLoS ONE  2011;6(6):e20287.
Visfatin has been proposed as an insulin-mimicking adipocytokine, predominantly secreted from adipose tissue and correlated with obesity. However, recent studies suggest visfatin may act as a proinflammatory cytokine. Our studies sought to determine the significance of this adipocytokine and its potential role in the pathogenesis of T2DM. Firstly, we examined the effects of diabetic status on circulating visfatin levels, and several other adipocytokines, demonstrating that diabetic status increased visfatin*, TNF-α*** and IL-6*** compared with non-diabetic subjects (*p<0.05, **p<0.01, ***p<0.001, respectively). We then assessed the effects of an insulin sensitizer, rosiglitazone (RSG), in treatment naïve T2DM subjects, on circulating visfatin levels. Our findings showed that visfatin was reduced post-RSG treatment [vs. pre-treatment (*p<0.05)] accompanied by a reduction in HOMA-IR**, thus implicating a role for insulin in visfatin regulation. Further studies addressed the intracellular mechanisms by which visfatin may be regulated, and may exert pro-inflammatory effects, in human abdominal subcutaneous (Abd Sc) adipocytes. Following insulin (Ins) and RSG treatment, our in vitro findings highlighted that insulin (100 nM), alone, upregulated visfatin protein expression whereas, in combination with RSG (10 nM), it reduced visfatin*, IKKβ** and p-JNK1/2*. Furthermore, inhibition of JNK protein exacted a significant reduction in visfatin expression (**p<0.01), whilst NF-κB blockade increased visfatin (*p<0.05), thus identifying JNK as the more influential factor in visfatin regulation. Additional in vitro analysis on adipokines regulating visfatin showed that only Abd Sc adipocytes treated with recombinant human (rh)IL-6 increased visfatin protein (*p<0.05), whilst rh visfatin treatment, itself, had no influence on TNF-α, IL-6 or resistin secretion from Sc adipocytes. These data highlight visfatin's regulation by insulin and RSG, potentially acting through NF-κB and JNK mechanisms, with only rh IL-6 modestly affecting visfatin regulation. Taken together, these findings suggest that visfatin may represent a pro-inflammatory cytokine that is influenced by insulin/insulin sensitivity via the NF-κB and JNK pathways.
doi:10.1371/journal.pone.0020287
PMCID: PMC3111427  PMID: 21694775
7.  Associations between Tissue Visfatin/Nicotinamide, Phosphoribosyltransferase (Nampt), Retinol Binding Protein-4, and Vaspin Concentrations and Insulin Resistance in Morbidly Obese Subjects 
Mediators of Inflammation  2013;2013:861496.
Visfatin/Nampt, vaspin, and retinol binding protein-4 (RBP-4) play an important role in insulin resistance. The objectives of this study were to measure visfatin/Nampt, vaspin, and RBP-4 concentrations in blood, liver, muscle, subcutaneous, omental, and mesenteric adipose tissues in morbidly obese subjects and investigate their relationship to insulin resistance. Blood and tissue samples were collected from 38 morbidly obese subjects during Roux-en-Y surgery. Insulin resistance biomarkers were measured using standard kits. Visfatin/Nampt, vaspin, and RBP-4 gene expression levels in tissues were measured using real-time PCR. Their protein concentrations in blood and tissues were measured using ELISA kits. Diabetic subjects had significantly higher homeostasis model of assessment-insulin resistance and age and lower blood HDL-cholesterol concentrations than nondiabetic and prediabetic subjects. Diabetic and prediabetic subjects had significantly higher blood concentrations of visfatin/Nampt and vaspin than nondiabetic subjects. Liver RBP-4 concentrations were positively associated with blood glucose concentrations. Blood insulin resistance biomarker levels were positively associated with visfatin/Nampt concentrations in omental adipose tissue and liver, and vaspin concentrations in mesenteric adipose tissue. In conclusion, the correlations of visfatin/Nampt, vaspin, and RBP-4 with insulin resistance are tissue dependent.
doi:10.1155/2013/861496
PMCID: PMC3866788  PMID: 24367155
8.  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
9.  Visfatin/Nampt: An Adipokine with Cardiovascular Impact 
Mediators of Inflammation  2013;2013:946427.
Adipose tissue is acknowledged as an endocrine organ that releases bioactive factors termed adipokines. Visfatin was initially identified as a novel adipokine with insulin-mimetic properties in mice. This adipokine was identical to two previously described molecules, namely, pre-B cell colony-enhancing factor (PBEF) and the enzyme nicotinamide phosphoribosyltransferase (Nampt). Enhanced circulating visfatin/Nampt levels have been reported in metabolic diseases, such as obesity and type 2 diabetes. Moreover, visfatin/Nampt circulating levels correlate with markers of systemic inflammation. In cardiovascular diseases, visfatin/Nampt was initially proposed as a clinical marker of atherosclerosis, endothelial dysfunction, and vascular damage, with a potential prognostic value. Nevertheless, beyond being a surrogate clinical marker, visfatin/Nampt is an active player promoting vascular inflammation, and atherosclerosis. Visfatin/Nampt effects on cytokine and chemokine secretion, macrophage survival, leukocyte recruitment by endothelial cells, vascular smooth muscle inflammation and plaque destabilization make of this adipokine an active factor in the development and progression of atherosclerosis. Further research is required to fully understand the mechanisms mediating the cellular actions of this adipokine and to better characterize the factors regulating visfatin/Nampt expression and release in all these pathologic scenarios. Only then, we will be able to conclude whether visfatin/Nampt is a therapeutical target in cardiometabolic diseases.
doi:10.1155/2013/946427
PMCID: PMC3697395  PMID: 23843684
10.  Visfatin Impairs Endothelium-Dependent Relaxation in Rat and Human Mesenteric Microvessels through Nicotinamide Phosphoribosyltransferase Activity 
PLoS ONE  2011;6(11):e27299.
Visfatin, also known as extracellular pre–B-cell colony–enhancing factor (PBEF) and nicotinamide phosphoribosyltransferase (Nampt), is an adipocytokine whose circulating levels are enhanced in metabolic disorders, such as type 2 diabetes mellitus and obesity. Circulating visfatin levels have been positively associated with vascular damage and endothelial dysfunction. Here, we investigated the ability of visfatin to directly impair vascular reactivity in mesenteric microvessels from both male Sprague-Dawley rats and patients undergoing non-urgent, non-septic abdominal surgery. The pre-incubation of rat microvessels with visfatin (50 and 100 ng/mL) did not modify the contractile response to noradrenaline (1 pmol/L to 30 µmol/L), as determined using a small vessel myograph. However, visfatin (10 to 100 ng/mL) concentration-dependently impaired the relaxation to acetylcholine (ACh; 100 pmol/L to 3 µmol/L), without interfering with the endothelium-independent relaxation to sodium nitroprusside (1 nmol/L to 3 µmol/L). In both cultured human umbilical vein endothelial cells and rat microvascular preparations, visfatin (50 ng/mL) stimulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, as determined by lucigenin-derived chemiluminiscence. The relaxation to ACh impaired by visfatin was restored by the NADPH oxidase inhibitor apocynin (10 µmol/L). Additionally, the Nampt inhibitor APO866 (10 mmol/L to 10 µmol/L), but not an insulin receptor-blocking antibody, also prevented the stimulation of NADPH oxidase and the relaxation impairment elicited by visfatin. Accordingly, the product of Nampt activity nicotinamide mononucleotide (100 nmol/L to 1 mmol/L) stimulated endothelial NADPH oxidase activity and concentration-dependently impaired ACh-induced vasorelaxation. In human mesenteric microvessels pre-contracted with 35 mmol/L potassium chloride, the endothelium-dependent vasodilation to bradykinin (1 nmol/L to 3 µmol/L) was equally impaired by visfatin and restored upon co-incubation with APO866. In conclusion, visfatin impairs endothelium-dependent relaxation through a mechanism involving NADPH oxidase stimulation and relying on Nampt enzymatic activity, and therefore arises as a potential new player in the development of endothelial dysfunction.
doi:10.1371/journal.pone.0027299
PMCID: PMC3207864  PMID: 22073309
11.  Adipocytokine Profile and Insulin Resistance in Childhood Obesity 
Mædica  2012;7(3):205-213.
ABSTRACT
Background: Adipose tissue is a veritable "endocrine organ" due to its adipocytokines secretion implied in insulin sensitivity modulation and cardiovascular complications.
Objective: To identify the adipocytokines' plasmatic profile (adiponectin, leptin, resistin, IL-6, TNFα) in obese children and adolescents and to assess their relationship with "classic" clinical/paraclinical markers of metabolic syndrome and insulin resistance.
Material and Methods: A case-control study comparing a study group of 38 obese children and adolescents (age 13.5±2.3 years) to a normal weight age matched control group of 24 children.
We measured body mass index (BMI) and waist circumference (WC), systolic and diastolic blood pressure (BP). The classical metabolic parameters (fasting glycemia, total cholesterol and its fractions, serum triglycerides) were measured in both groups. Insulin sensitivity was evaluated using fasting insulinemia, HOMA-index and insulin-resistance summary score (IRS). Adiponectin, leptin, resistin, IL-6 and TNFα were measured using ELISA method.
Outcomes: Serum levels of leptin, resistin and IL-6 were signficantly higher (42.42±22.58 ng/ml versus 14.4±14.49 ng/ml, p <0.001; 9.69±3.47 ng/ml versus 7.92±2.13ng/ml, p = 0.029 and 2.66 ±2.87 pg/ml versus 0.89 ± 1.16 pg/ml, p = 0.006 respectively), while adiponectin levels were significantly lower (9.05±4.61 µg/ml versus 15.93±9.24 μg/ml, p <0.001) in the obese group compared to control group. TNFα was not statistical different between groups.
In multivariate regression analysis adiponectin was negatively and significantly correlated with WC (r = - 0.463, p = 0.003); leptin was positively and significantly related to WC, diastolic BP, fasting insulinemia and resistin (r = 0.775, p <0.001); resistin was positively related to leptin and IL-6 (r = 0.499, p <0.001), IL-6 was positively and significantly related to diastolic blood pressure (r = 0.333, p = 0.008).
Conclusions: Serum levels of adiponectin, leptin, resistin and IL-6 are significantly different in obese children compared to normal weight controls; leptin was the only adipokine correlated with insulin resistance in children. There are significant correlations between plasmatic levels of leptin, resistin and IL-6.
Simple plasmatic determination of TNFα is not a marker of the degree of obesity or its metabolic complications in pediatric population.
PMCID: PMC3566883  PMID: 23400230
adipokine; cytokine; obesity; children
12.  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
13.  Adipokines as Possible New Predictors of Cardiovascular Diseases: A Case Control Study 
Background and Aims. The secretion of several adipocytokines, such as adiponectin, retinol-binding protein 4 (RBP4), adipocyte fatty acid binding protein (aFABP), and visfatin, is altered in subjects with abdominal adiposity; these endocrine alterations could contribute to increased cardiovascular risk. The aim of the study was to assess the relationship among adiponectin, RBP4, aFABP, and visfatin, and incident cardiovascular disease. Methods and Results. A case-control study, nested within a prospective cohort, on 2945 subjects enrolled for a diabetes screening program was performed. We studied 18 patients with incident fatal or nonfatal IHD (Ischemic Heart Disease) or CVD (Cerebrovascular Disease), compared with 18 matched control subjects. Circulating adiponectin levels were significantly lower in cases of IHD with respect to controls. Circulating RBP4 levels were significantly increased in CVD and decreased in IHD with respect to controls. Circulating aFABP4 levels were significantly increased in CVD, while no difference was associated with IHD. Circulating visfatin levels were significantly lower in cases of both CVD and IHD with respect to controls, while no difference was associated with CVD. Conclusions. The present study confirms that low adiponectin is associated with increased incidents of IHD, but not CVD, and suggests, for the first time, a major effect of visfatin, aFABP, and RBP4 in the development of cardiovascular disease.
doi:10.1155/2012/253428
PMCID: PMC3160046  PMID: 21869928
14.  Study of Comparative Effects of Antioxidants on Insulin Sensitivity in Type 2 Diabetes Mellitus 
Objectives
This study intended to assess the effects of the antioxidants; Alpha Lipoic Acid (ALA), omega 3 fatty acids and vitamin E on the parameters of insulin sensitivity, oxidative stress, lipid metabolism and glycaemic control in patients of type 2 diabetes mellitus.
Methods
This was a prospective, randomized, double blind, placebo controlled, single centred study. One hundred four patients with type 2 diabetes mellitus with insulin resistance were recruited for the study. They were given ALA, omega 3 fatty acids, vitamin E or placebo. Their weight, Body Mass Index (BMI) and Waist circumference were measured. The investigations which were fasting glucose and fasting total cholesterol. The insulin resistance was calculated on the basis of the BMI and the waist circumference.
Results
In the intra group analysis at the baseline (V1) vs at the end of the treatment period (V5), we observed a significant decrease in the BMI, waist circumference and the total cholesterol in the three treatment groups. In the intergroup analysis at V5, ALA, omega 3 fatty acids and vitamin E showed a significant improvement in the total cholesterol as compared to the placebo and vitamin E showed the maximum improvement.
Conclusion
ALA, omega 3 fatty acids and vitamin E showed the improvement in insulin sensitivity. Since they differ in improving different parameters all of these three can be used as an add on therapy in patients with type 2 diabetes mellitus to improve their insulin sensitivity and lipid metabolism.
doi:10.7860/JCDR/2012/4464.2535
PMCID: PMC3527772  PMID: 23285432
Insulin resistance; Alpha lipoic acid; Omega 3 fatty acid; Vitamin E
15.  MATERNAL VISFATIN CONCENTRATION IN NORMAL PREGNANCY 
Journal of perinatal medicine  2009;37(3):206-217.
Objective
Adipose tissue has now emerged as a powerful endocrine organ via the production of adipokines. Visfatin, a novel adipokine with diabetogenic and immunomodulatory properties has been implicated in the pathophysiology of insulin resistance in patients with obesity and Type-2 diabetes mellitus. The aim of this study was to determine whether there are changes in the maternal plasma concentration of visfatin with advancing gestation and as a function of maternal weight.
Study design
In this cross-sectional study, maternal plasma concentrations of visfatin were determined in normal weight and overweight/obese pregnant women in the following gestational age groups: 1) 11–14 weeks (n= 52); 2) 19–26 weeks (n=68); 3) 27–34 weeks (n=93); and 4) >37 weeks (n=60). Visfatin concentrations were determined by ELISA. Non parametric statistics were used for analysis.
Results
1) The median maternal plasma visfatin concentration was higher in pregnant women between 19–26 weeks of gestation than that of those between 11–14 weeks of gestation (p<0.01) and those between 27–34 weeks of gestation (p <0.01); 2) among normal weight pregnant women, the median plasma visfatin concentrations of women between 19–26 weeks of gestation was higher than that of those between 11–14 weeks (p<0.01) and those between 27–34 weeks (p < 0.01); and 3) among overweight/obese patients, the median maternal visfatin concentration was similar between the different gestational age groups
Conclusion
The median maternal plasma concentration of visfatin peaks between 19–26 and has a nadir between 27–34 weeks of gestation. Normal and overweight/obese pregnant women differed in the pattern of changes in circulating visfatin concentrations as a function of gestational age.
doi:10.1515/JPM.2009.054
PMCID: PMC3500641  PMID: 19284295
Visfatin; pregnancy; adipokines; overweight; obesity
16.  Serum Visfatin and Fetuin-A Levels and Glycemic Control in Patients with Obese Type 2 Diabetes Mellitus 
Diabetes & Metabolism Journal  2011;35(5):523-528.
Background
Visfatin is an adipokine produced by visceral adipose tissue and has insulin-mimicking effects. Fetuin-A is a hepatic secretory protein that binds the insulin receptor and inhibits insulin action both in vivo and in vitro. The authors of the present study aimed to investigate the levels of serum visfatin and fetuin-A and their correlation with hemoglobin A1c (HbA1c) and urine albumin levels in patients with type 2 diabetes mellitus (T2DM).
Methods
A total of 40 obese patients with T2DM (11 males and 29 females; age, 54.47±10.83 years and 23 obese nondiabetic controls (8 males and 15 females; age, 53.04±11.33 years) were included in the study. Age, sex, and body mass index were similar in the 2 groups. Serum visfatin and fetuin-A levels were measured by enzyme-linked immunosorbent assay. HbA1c and urine albumin levels were measured by high performance liquid chromatography and nephelometric method, respectively.
Results
Serum levels of visfatin in patients with T2DM (4.03±2.44 ng/mL) were similar to the control group (3.65±3.02 ng/mL). Serum fetuin-A levels were significantly lower in patients with T2DM than the controls (298.75±78.86 and 430.73±94.46 µg/mL, respectively). HbA1c levels were significantly higher in the T2DM group compared with controls (7.33±1.32 and 5.44±0.84%, respectively). Correlations between visfatin, fetuin-A and HbA1c levels were not observed.
Conclusion
The present study suggests fetuin-A may play a role in the pathogenesis of T2DM.
doi:10.4093/dmj.2011.35.5.523
PMCID: PMC3221028  PMID: 22111044
Albuminuria; Diabetes mellitus, type 2; Fetuin-A; Hemoglobin A1c; Visfatin
17.  Prediction of metabolic syndrome in women with polycystic ovary syndrome 
Objective
To identify biochemical factors that serve as predictors for the metabolic syndrome (MetS) in patients with polycystic ovary syndrome (PCOS) and to investigate the value of adipocytokines in the prediction of metabolic syndrome.
Material and Methods
A total of 91 pre-menopausal women with PCOS diagnosed according to the Rotterdam consensus criteria were recruited as study subjects. Waist circumference, blood pressure, body mass index (BMI), fasting glucose, serum lipids, insulin, FSH, LH, E2, total testosteron, homeostatic model assessment–insulin resistance (HOMA-IR), serum leptin and adiponectin levels were evaluated for all patients.
Results
Of the 91 women with PCOS, 15 patients met the criteria for MetS. Body weight, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, and VLDL concentrations were significantly higher and HDL was significantly lower in women with PCOS+MetS compared with those with PCOS only. However, the level of LDL, FSH, LH, E2 and total testesterone was not significantly different between these two groups. Women with PCOS+MetS had significantly higher levels of leptin and HOMA-IR, and significantly lower levels of adiponectin compared to the women with PCOS only. In the multiple logistic regression model, the association between HOMA-IR and leptin, and MetS remained statistically significant (p=0.001 and 0.018), while the association between adiponectin and MetS was no longer statistically significant.
Conclusion
Aside from the biochemical markers such as glucose, cholesterol and triglyceride, adipose tissue factors and insulin resistance are valuable parameters in the prediction of MetS in patients with PCOS.
doi:10.5152/jtgga.2012.24
PMCID: PMC3939237  PMID: 24592034
Metabolic syndrome; polycystic ovary syndrome; leptin; adiponectin; HOMA-IR
18.  Visfatin, glucose metabolism and vascular disease: a review of evidence 
The adipose tissue is an endocrine organ producing substances called adipocytokines that have different effects on lipid metabolism, metabolic syndrome, and cardiovascular risk. Visfatin was recently described as an adipocytokine with potentially important effects on glucose metabolism and atherosclerosis. Visfatin has been linked to several inflammatory conditions, beta cell function, and cardiovascular disease. The growing number of publications on the subject shall bring further evidence about this adipocytokine. Its findings may contribute in the identification of higher risk individuals for diabetes and cardiovascular disease with a better comprehension about the complex intercorrelation between adiposity, glucose metabolism and vascular disease.
doi:10.1186/1758-5996-2-21
PMCID: PMC2857825  PMID: 20346149
19.  Leptin, resistin and visfatin: the missing link between endocrine metabolic disorders and immunity 
Adipose tissue is still regarded as a principle site for lipid storage and mobilizing tissue with an important role in the control of energy homeostasis. Additionally, adipose tissue-secreted hormones such as leptin, visfatin, resistin, apelin, omentin, sex steroids, and various growth factors are now regarded as a functional part of the endocrine system. These hormones also play an important role in the immune system. Several in vitro and in vivo studies have suggested the complex role of adipocyte-derived hormones in immune system and inflammation. Adipokines mediate beneficial and detrimental effects in immunity and inflammation. Many of these adipocytokines have a physiological role in metabolism. The uncontrolled secretions of several adipocytokines were associated with the stimulation of inflammatory processes leading to metabolic disorders including obesity, atherosclerosis, insulin resistance and type 2 diabetes. Obesity leads to the dysfunction of adipocytes andcorrelated with the imbalance of adipokines levels. In obese and diabetic conditions, leptin deficiency inhibited the Jak/Stat3/PI3K and insulin pathways. In this review, ample evidence exists to support the recognition of the adipocyte’s role in various tissues and pathologies. New integral insights may add dimensions to translate any potential agents into the future clinical armamentarium of chronic endocrine metabolic and inflammatory diseases. Functional balance of both adipocytes and immune cells is important to exert their effects on endocrine metabolic disorders; furthermore, adipose tissue should be renamed not only as a functional part of the endocrine system but also as a new part of the immune system.
doi:10.1186/2047-783X-18-12
PMCID: PMC3655867  PMID: 23634778
Adipocytokines; Obesity; Diabetes; Endocrine; Immunity
20.  Lipid Profiles and Serum Visfatin Concentrations in Patients with Type II Diabetes in Comparison with Healthy Controls 
Background:
Visfatin is a new adipocytokine which is largely secreted by visceral adipose tissue and its effects in the development of diabetes and inflammatory reactions are similar to insulin. It acts synergistically with insulin in increasing glucose cellular uptake, stimulating glucose transfer to the muscle and adipose tissue, as well as in preventing hepatic glucose production. Its insulin-like effects are mediated through direct connection and activation of insulin receptors without any change or competition with the insulin.
Methods:
This case-control study was conducted among 64 women consisting of 32 diabetic patients, and 32 age-matched healthy controls. The case group consisted of 32 post-menopausal diabetic women, aged 45-65 years. Those patients were eligible who had a history of at least five years of type II diabetes, without any complications of diabetes, and who were treated only by oral glucose-lowering medications. Those individuals with C-reactive protein (CRP) test of 3+ and above were excluded from the study. Results were compared with age- and sex- matched controls.
Results:
Average visfatin level was significantly higher in diabetic patients than in controls (4.3 ± 1.06ng/dl vs. 3.15 ± 0.74ng/dl, respectively< 0.001).
The mean values of anthropometric indexes and lipid profile were not significantly different between diabetic patients and controls
Conclusion:
This study documented an inverse relationship between circulating level of visfatin and fasting blood glucose. This finding may suggest the role of increased visfatin level and increase in synthesis and secretion of the cytokines from adipocytes. These findings may be useful for primary and secondary preventive issues in diabetic and pre-diabetic individuals.
PMCID: PMC3372075  PMID: 22708029
Lipid profile; type II diabetes; visfatin
21.  Relationship Between Cerebrospinal Fluid Visfatin (PBEF/Nampt) Levels and Adiposity in Humans 
Diabetes  2009;58(3):637-640.
OBJECTIVE—Observations of elevated circulating concentrations of visfatin (PBEF/Nampt) in obesity and diabetes suggest that this recently described adipokine is involved in the regulation of body weight and metabolism. We examined in humans whether visfatin is found in cerebrospinal fluid (CSF) and, if so, how CSF visfatin concentrations relate to adiposity and metabolic parameters.
RESEARCH DESIGN AND METHODS—We measured visfatin concentrations in the plasma and CSF of 38 subjects (18 men and 20 women; age 19–80 years) with a wide range of body weight (BMI 16.24–38.10 kg/m2). In addition, anthropometric parameters and endocrine markers were assessed. Bivariate correlation coefficients were determined and stepwise multiple regression analyses were performed to detect associations of CSF and plasma visfatin levels with relevant parameters.
RESULTS—Plasma visfatin levels increased with rising BMI (P < 0.0001) and body fat mass (P < 0.0001). In contrast, CSF visfatin levels decreased with increasing plasma visfatin concentrations (P < 0.03), BMI (P < 0.001), body fat mass (P < 0.0001), and insulin resistance (P < 0.05). Body fat was the only factor independently associated with CSF visfatin, explaining 58% of the variation of CSF visfatin levels (P < 0.0001). Neither plasma (P > 0.13) nor CSF (P > 0.61) visfatin concentrations differed between men and women.
CONCLUSIONS—Our data indicate that visfatin concentrations in human CSF decrease with rising body fat, supporting the assumption that visfatin transport across the blood-brain barrier is impaired in obesity and that central nervous visfatin insufficiency or resistance are linked to pathogenetic mechanisms of obesity.
doi:10.2337/db08-1176
PMCID: PMC2646062  PMID: 19095760
22.  Cardiovascular risk factor management of myocardial infarction patients with and without diabetes in the Netherlands between 2002 and 2006: a cross-sectional analysis of baseline data 
BMJ Open  2012;2(6):e001360.
Objective
We examined levels and trends in cardiovascular risk factors and drug treatment in myocardial infarction (MI) patients with and without diabetes.
Design
Cross-sectional analysis of baseline Alpha Omega Trial data, a randomised controlled trial.
Setting
32 hospitals in the Netherlands.
Participants
In total, we had 1014 MI patients with diabetes (74% men) and 3823 without diabetes (79% men) aged 60–80 years, analysed over the period 2002–2006.
Results
Between 2002 and 2006, a significantly decreasing trend in the prevalence of obesity (−5%, ptrend=0.02) and in systolic blood pressure (BP) levels (−5 mm Hg, ptrend<0.0001) was demonstrated in non-diabetic patients, but not in diabetic patients. In 2006, obesity, mean systolic BP and serum triglyceride levels were significantly higher, whereas high-density lipoprotein cholesterol levels were lower in diabetic patients compared to those without. Prescription of antihypertensive drug (diabetic vs non-diabetic patients respectively, 95% vs 93%, p=0.08) and statin treatment were high (86% and 90%, p=0.11).
Conclusions
A high proportion of MI patients with and without diabetes was similarly treated with cardiovascular drugs. In spite of high drug treatment levels, more adverse risk factors were found in patients with diabetes.
doi:10.1136/bmjopen-2012-001360
PMCID: PMC3532965  PMID: 23117562
Epidemiology; Preventive Medicine
23.  Omega-3 Augmentation of Sertraline in the Treatment of Depression In Patients with Coronary Heart Disease: A Randomized Controlled Trial 
Studies of depressed psychiatric patients have shown that antidepressant efficacy can be increased by augmentation with omega-3 fatty acids (FAs). The purpose of this study was to determine whether omega-3 augmentation improves the response to sertraline in patients with major depression and documented coronary heart disease (CHD). One hundred twenty-two patients with major depression and CHD were given 50 mg/day of sertraline (Zoloft™) and randomized in double-blind fashion to 2g/day of omega-3 (Lovaza™) or to corn oil placebo capsules. Adherence to the medication regimen was 97% in both groups for both medications. The levels of omega-3 (percent DHA+EPA in red blood cells) were nearly identical between the groups at baseline; the level changed during the intervention phase in the omega-3 arm to the expected level, but it remained stable in the placebo arm. Neither weekly Beck Depression Inventory (BDI-II) scores (p = .38) nor pre-post BDI-II scores (p = .44) differed between the omega-3 and placebo groups. The rates of depression remission (BDI-II ≤ 8) and response (>50% reduction in BDI-II from baseline) were also nearly identical. In conclusion, this trial yielded no evidence that omega-3 augmentation increases the efficacy of sertraline for comorbid major depression in CHD. Whether higher doses of omega-3, longer treatment, or the use of omega-3 as a monotherapy can improve depression in patients with stable heart disease remains to be determined.
doi:10.1001/jama.2009.1487
PMCID: PMC3477788  PMID: 19843899
24.  Serum Visfatin Levels, Adiposity and Glucose Metabolism in Obese Adolescents 
Objective: Visfatin, an adipokine, has insulin-mimetic effects. The main determinants of both the production and the physiologic role of visfatin are still unclear. The aim of this study is to determine the relation of serum visfatin to adiposity and glucose metabolism.
Methods: 40 pubertal adolescents (20 females, 20 males; age range: 9-17 years) with exogenous obesity and 20 age- and sex-matched healthy adolescents (10 females, 10 males) were enrolled in the study. Oral glucose tolerance test (OGTT) was performed in the obese group. Serum glucose, insulin and visfatin levels were analyzed in the fasting state in the controls and at 0, 60 and 120 minutes during the OGTT in the obese group.
Results: The obese group had higher serum visfatin levels than the control group [11.6 (3.3-26) ng/mL vs. 7.5 (3.3-10.5) ng/mL, p<0.001]. Visfatin levels were correlated positively with body mass index, waist/hip ratio, insulin, and homeostasis model assessment for insulin resistance and negatively with glucose/insulin ratio in the combined group (obese subjects plus controls). Visfatin levels were essentially similar in obese subjects with and without insulin resistance (p>0.05). Serum visfatin levels did not change at 60 and 120 minutes of the OGTT compared to the baseline levels (p>0.05).
Conclusions: Serum visfatin levels are elevated in obese adolescents and do not change with acute changes in glucose metabolism. Visfatin levels are related with adiposity and glucose metabolism parameters. However, the role and contribution of adiposity and glucose metabolism to the circulating visfatin levels in obese patients remain to be explored.
Conflict of interest:None declared.
doi:10.4274/Jcrpe.547
PMCID: PMC3386777  PMID: 22672864
Visfatin; Obese; insulin resistance; glucose tolerance test
25.  Maternal and Neonatal Circulating Visfatin Concentrations in Patients with Preeclampsia and a Small-For-Gestational Age Neonate 
Objective
Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age AGA neonate or in those with preeclampsia. It has been proposed that enhanced transfer of visfatin from the fetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: 1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of preeclamptic mothers; and 2) to assess the relationship between maternal and fetal circulating visfatin concentrations in patients with an SGA neonate and those with preeclampsia.
Study design
This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: 1) 44 normal pregnant women at term and their AGA neonates; 2) 22 normotensive pregnant women and their SGA neonates; 3) 22 women with preeclampsia and their neonates; and 4) 22 preterm neonates delivered following spontaneous preterm labor without funisitis or histologic chorioamnionitis, matched for gestational age with infants of preeclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses.
Results
1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and preeclampsia groups (p<0.001 for all comparisons); 2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with preeclampsia and their gestational-age-matched preterm AGA neonates; 3) maternal and cord blood visfatin concentrations correlated only in the normal term group (r= 0.48, p=0.04).
Conclusion
Circulating visfatin concentrations are lower in the fetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the fetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate.
doi:10.3109/14767050903572190
PMCID: PMC3413321  PMID: 20121389
visfatin; adipokines; cytokine; pregnancy; fetal growth restriction; AGA; umbilical cord blood

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