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1.  The effect of omega-3 on the serum visfatin concentration in patients with type II diabetes 
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.
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.
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).
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.  Relationship between blood peroxidases activity and visfatin levels in metabolic syndrome patients 
ARYA Atherosclerosis  2014;10(4):218-226.
The observed relationships between visfatin, peroxidases activity, and metabolic syndrome (MetS) are inconsistent; therefore, this study was undertaken to understand these relationships.
This cross-sectional study was conducted as a part of the Isfahan Healthy Heart Program, Iran. A blood sample of 90 MetS and non-MetS patients were used to estimate total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), fasting blood glucose (FBG), waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP), visfatin and peroxidases activity. Data analysis for MetS group was carried out in two ways. (1) MetS with three components and with > 3 components. (2) MetS with hyperglycemia and without hyperglycemia.
SBP, DBP, WC, FBG, TC, TG, LDL-C, and were higher and HDL-C levels was lower in MetS patients. There was a significant correlation between visfatin levels and peroxidases activity in MetS patients with three components. Levels of visfatin were significantly higher in male as compared to female subjects in the MetS with three components group. There was a significant decrease in peroxidases activity in > 45 years old subjects in the MetS with > 3 components group. A significant correlation was observed between serum visfatin levels and FBG in the MetS without hyperglycemia group.
Peroxidases activities in MetS patients can be related to visfatin levels. Gender influences on peroxidases activity probably and was lower in female patients with MetS. Hyperglycemia does not influence peroxidases activities and visfatin levels.
PMCID: PMC4173313  PMID: 25258638
Peroxidase; Metabolic Syndrome; Visfatin
3.  Adipokines Vaspin and Visfatin in Obese Children 
Adipokines provides new insights about the physiology, pathology and treatment of obesity.
We investigated the association between serum vaspin and serum visfatin concentrations with obesity in Egyptian children.
Twenty two obese children with body mass index (BMI) above 95th percentile; 11 males and 11 females were included in this study. Their mean age was 9.18 ± 2.8 years. After general clinical examination, fasting blood glucose, triglycerides, total cholesterol and high density lipoprotein cholesterol were measured in cases and controls (n=11). Fasting insulin, vaspin and visfatin were detected using ELIZA. Insulin resistance was estimated by Homeostasis model assessment method (HOMA-IR).
Blood pressure, in both systolic and diastolic measurements was elevated significantly in obese children. Significant elevation of serum insulin and insulin resistance (HOMA/IR) were observed in obese children too. Vaspin and visfatin showed significant elevation in obese children than controls. Significant positive correlations were detected between visfatin and BMI, waist circumference, hip circumference and HOMA/IR. We found that Vaspin and visfatin are higher in obese children.
Visfatin but not vaspin correlates positively with waist circumference and HOMA/IR in obese children.
PMCID: PMC4877888  PMID: 27275288
Vaspin; visfatin; obese; children; adipokines
4.  Circulating visfatin level and visfatin/insulin ratio in obese women with metabolic syndrome 
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.
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).
We conclude that the visfatin/insulin ratio declining with increasing visceral obesity may predispose to the development of insulin resistance.
PMCID: PMC3361032  PMID: 22661992
visfatin; insulin; obesity; metabolic syndrome
5.  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.
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.
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.
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.
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
6.  In-vitro function of upstream visfatin polymorphisms that are associated with adverse cardiometabolic parameters in obese children 
BMC Genomics  2016;17:974.
Visfatin is an adipokine associated with glucose and lipid metabolism. We previously reported two visfatin upstream single nucleotide polymorphisms (SNPs), c.-3187G > A (rs11977021) and c.-1537C > T (rs61330082), which were in perfect linkage disequilibrium, in a Singaporean cohort of severely obese children and are associated with visfatin level and adverse cardiometabolic parameters. We aim to functionally characterize the effect of c.-3187G > A and c.-1537C > T SNPs on basal transcriptional activity.
A 1.6 kb and 3.7 kb upstream promoter region of the visfatin gene was amplified by polymerase chain reaction and separately cloned into luciferase reporter vectors. Successful clones were transfected into human embryonic kidney (HEK293T) and human breast carcinoma (MCF7) cells and in-vitro dual-luciferase assay was performed. Electrophoretic mobility shift assay (EMSA) was also conducted to examine the binding affinity between transcription factors and visfatin promoter sequences.
Variant promoter with only c.-1537C > T SNP did not show a change in transcriptional activity as compared to the wild type. However, variant promoter with both c.-3187G > A and c.-1537C > T SNPs showed a statistically significant increase of 1.41 fold (p < 0.01) in transcriptional activity. The longer 3.7kbp visfatin promoter sequence was also shown to have significantly higher transcriptional activity (p < 0.05) as compared to the shorter 1.6kbp visfatin promoter. Both c.-3187G > A and c.-1537C > T variants showed an increased binding with nuclear protein.
Discussion and conclusions
We have demonstrated for the first time that visfatin variant promoter with both c.-3187G > A and c.-1537C > T SNPs result in an increase in transcriptional activity. This supports our previous finding and postulation that these SNPs contribute to elevated visfatin levels which may mediate higher triglyceride levels, severe systolic blood pressure and severe hypertension in obese children. These SNPs may co-operatively affect enhancer or silencer function to regulate transcriptional activity. In conclusion, this study shows that upstream visfatin SNPs could potentially affect phenotypic outcome in obese children through alteration of circulating visfatin level.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-016-3315-9) contains supplementary material, which is available to authorized users.
PMCID: PMC5124300  PMID: 27887573
Childhood obesity; Visfatin promoter; Luciferase assay; Polymorphisms; Variants
7.  Effects of 12 Weeks of Combined Exercise Training on Visfatin and Metabolic Syndrome Factors in Obese Middle-Aged Women 
Visfatin is a highly expressed protein with insulin-like functions located predominantly in visceral adipose tissue and has been linked to obesity and increased health risks. The purpose of this study was to examine the effects of 12 weeks of combined exercise training on visfatin and metabolic syndrome factors in obese middle-aged women. Subjects were randomly assigned to either a training (n = 10) or control (n = 10) group. The training group exercised for 1 hour, 3 days per week during the 12 week supervised training program. The training program included 3 sets of 10 repetition maximum (10RM) resistance exercise as well as aerobic exercise at an intensity of 60-70% of their heart rate reserve (HRR). The control group was asked to maintain their normal daily activities. Two-way (group X time) repeated measured analysis of variance revealed no significant main effects, but there was a significant group X time interaction for the following variables: body weight (p < 0.01), percent body fat (% fat) (p < 0.01), waist hip ratio (WHR) (p < 0.01), diastolic blood pressure (DBP) (p < 0.05), fasting glucose level (p < 0.01), triglyceride levels (TG) (p < 0.01), high density lipoprotein cholesterol levels (HDL-C) (p < 0.05), and visfatin (p < 0.01). In conclusion, the 12 week combined resistance and aerobic training program used in this study was very effective for producing significant benefits to body composition and metabolic syndrome factors, as well as lowering visfatin levels in these obese middle-aged women.
Key pointsRecent studies have linked visfatin to obesity and increased health risks.The study was done to investigate the effects of 12 weeks of combined exercise training on visfatin and metabolic syndrome factors in obese middle-aged women.The exercise program used in this study was found to be very effective for lowering visfatin levels in obese middle-aged women.
PMCID: PMC3737906  PMID: 24149317
Metabolic syndrome; combined resistance; aerobic exercise; visfatin
8.  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.
PMCID: PMC2646062  PMID: 19095760
9.  Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies 
Lancet  2011;377(9784):1085-1095.
Guidelines differ about the value of assessment of adiposity measures for cardiovascular disease risk prediction when information is available for other risk factors. We studied the separate and combined associations of body-mass index (BMI), waist circumference, and waist-to-hip ratio with risk of first-onset cardiovascular disease.
We used individual records from 58 cohorts to calculate hazard ratios (HRs) per 1 SD higher baseline values (4·56 kg/m2 higher BMI, 12·6 cm higher waist circumference, and 0·083 higher waist-to-hip ratio) and measures of risk discrimination and reclassification. Serial adiposity assessments were used to calculate regression dilution ratios.
Individual records were available for 221 934 people in 17 countries (14 297 incident cardiovascular disease outcomes; 1·87 million person-years at risk). Serial adiposity assessments were made in up to 63 821 people (mean interval 5·7 years [SD 3·9]). In people with BMI of 20 kg/m2 or higher, HRs for cardiovascular disease were 1·23 (95% CI 1·17–1·29) with BMI, 1·27 (1·20–1·33) with waist circumference, and 1·25 (1·19–1·31) with waist-to-hip ratio, after adjustment for age, sex, and smoking status. After further adjustment for baseline systolic blood pressure, history of diabetes, and total and HDL cholesterol, corresponding HRs were 1·07 (1·03–1·11) with BMI, 1·10 (1·05–1·14) with waist circumference, and 1·12 (1·08–1·15) with waist-to-hip ratio. Addition of information on BMI, waist circumference, or waist-to-hip ratio to a cardiovascular disease risk prediction model containing conventional risk factors did not importantly improve risk discrimination (C-index changes of −0·0001, −0·0001, and 0·0008, respectively), nor classification of participants to categories of predicted 10-year risk (net reclassification improvement −0·19%, −0·05%, and −0·05%, respectively). Findings were similar when adiposity measures were considered in combination. Reproducibility was greater for BMI (regression dilution ratio 0·95, 95% CI 0·93–0·97) than for waist circumference (0·86, 0·83–0·89) or waist-to-hip ratio (0·63, 0·57–0·70).
BMI, waist circumference, and waist-to-hip ratio, whether assessed singly or in combination, do not importantly improve cardiovascular disease risk prediction in people in developed countries when additional information is available for systolic blood pressure, history of diabetes, and lipids.
British Heart Foundation and UK Medical Research Council.
PMCID: PMC3145074  PMID: 21397319
10.  Omega-3 Polyunsaturated Fatty Acids Increase Plasma Adiponectin to Leptin Ratio in Stable Coronary Artery Disease 
Cardiovascular Drugs and Therapy  2013;27(4):289-295.
Growing evidence suggests a cardioprotective role of omega-3 polyunsaturated fatty acids (PUFA). However, the exact mechanisms underlying the effects of omega-3 PUFA in humans have not yet been fully clarified.
We sought to evaluate omega-3 PUFA-mediated effects on adipokines in patients with stable coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI).
We conducted a prospective, double-blind, placebo-controlled, randomized study, in which adiponectin, leptin and resistin were determined at baseline, 3–5 days and 30 days during administration of omega-3 PUFA 1 g/day (n = 20) or placebo (n = 28).
As compared to controls administration of omega-3 PUFA resulted in increase of adiponectin by 13.4 % (P < 0.0001), reduction of leptin by 22 % (P < 0.0001) and increase of adiponectin to leptin (A/L) ratio by 45.5 % (P < 0.0001) at 30 days, but not at 3–5 days. Compared with placebo adiponectin was 12.7 % higher (P = 0.0042), leptin was 16.7 % lower (P < 0.0001) and A/L ratio was 33.3 % higher (P < 0.0001) in the omega-3 PUFA group at 30 days. Resistin decreased similarly in both groups after 1 month, without intergroup differences (P = 0.32). The multivariate model showed that the independent predictors of changes in adiponectin at 1 month (P < 0.001) were: omega-3 PUFA treatment, baseline platelet count, total cholesterol and those in leptin (P < 0.0001) were: omega-3 PUFA treatment and waist circumference. Independent predictors of A/L ratio changes (P < 0.0001) were: assigned treatment, current smoking and hyperlipidemia.
In high risk stable coronary patients after PCI omega-3 PUFA supplementation improves adipokine profile in circulating blood. This might be a novel, favourable mechanism of omega-3 PUFA action.
Electronic supplementary material
The online version of this article (doi:10.1007/s10557-013-6457-x) contains supplementary material, which is available to authorized users.
PMCID: PMC3709088  PMID: 23584593
Omega-3 polyunsaturated fatty acids; Adiponectin; Leptin; Resistin; Stable coronary artery disease; Percutaneous coronary intervention
11.  Independent Association of Waist Circumference With Hypertension and Diabetes in African American Women, South Carolina, 2007–2009 
Obesity is associated with hypertension and diabetes, which are independent risk factors for cardiovascular disease (CVD); 53% of African American women are obese. Of the approximately 44% of African American women who are hypertensive, more than 87% are overweight or obese. Additionally, more than twice as many African American women (13.1%) as white women (6.1%) have been diagnosed with type 2 diabetes. Obesity is usually measured using body mass index (BMI). However, abdominal adiposity may be more predictive of CVD risk than BMI. This study investigates the independent association of waist circumference with hypertension and diabetes in African American women.
As part of the Faith, Activity, and Nutrition (FAN) program, we recruited 843 African American women (mean age 53.8 y [SD, 14.1 y]) from African Methodist Episcopal churches. If a participant reported she had hypertension or had measured systolic blood pressure at or higher than 140 mm Hg or measured diastolic blood pressure at or higher than 90 mm Hg, she was classified as having hypertension. To assess increased health risks associated with waist circumference, we used the World Health Organization’s standards to categorize waist circumference as normal risk (waist circumference <80 cm), increased risk (waist circumference 80–88 cm), or substantially increased risk (waist circumference >88 cm). We used logistic regression models to test predictors of hypertension and diabetes.
Of 843 study participants, 205 had diabetes and 545 were hypertensive. Women with a waist circumference of 88 cm or more were at increased risk for hypertension (odds ratio [OR] = 7.17, P < .002) and diabetes (OR = 6.99, P < .001). Associations remained after controlling for all variables (hypertension OR = 5.53, P < .001; diabetes, OR = 5.38, P < .001).
After controlling for all variables, waist circumference was independently associated with a 5-fold risk in hypertension and diabetes in African American women.
PMCID: PMC3457765  PMID: 22632742
12.  Relation of Osteoprotegerin, Visfatin and Ghrelin to Metabolic Syndrome in Type 2 Diabetic Patients 
It is now realized that insulin resistance plays a principal role in initiating the pathologic manifestations of the metabolic syndrome (MetS).
The aim of this study was to assess the possible role of osteoprotegerin, visfatin and ghrelin in the pathogenesis of MetS among type 2 diabetes mellitus (T2DM).
Design and methods
Serum blood samples were obtained from 116 subjects (39 T2DM; 48 T2DM with MetS; 29 healthy controls). Glycemic status and lipid profile were assessed by enzymatic method. Osteoprotegerin, visfatin, ghrelin and insulin were measured by ELISA method.
Osteoprotegerin and visfatin were significantly higher, while ghrelin was significantly lower in diabetic patients compared to healthy control group (p<0.05). Moreover, Osteoprotegerin and visfatin showed significant higher levels in T2DM patients with MetS than those without MetS (p<0.05). The best cut-off values for the investigated markers were determined by ROC curve. Osteoprotegerin (1.06 ng/mL), visfatin (32.27 ng/mL) and ghrelin (33.65 pg/mL) presented sensitivity of 76%, 92% and 39.1%; respectively and specificity of 41%, 69.2% and 62.9%; respectively, in predicting MetS among T2DM. Among the investigated parameters, Visfatin was the one which predicts MetS among diabetic patients [AUC=0.88, p<0.05].
Osteoprotegerin, visfatin and ghrelin might be implicated in the pathogenesis of diabetes. Moreover, osteoprotegerin and visfatin may have additional potential role in the development of the metabolic syndrome. Visfatin was superior among studied parameters in predicting MetS among T2DM.
PMCID: PMC4538889  PMID: 26309431
Osteoprotegerin; Visfatin; Ghrelin; Diabetes; Insulin Resistance; Type 2 diabetes mellitus and Metabolic Syndrome
13.  Age and sex-specific associations of anthropometric measures of adiposity with blood pressure and hypertension in India: a cross-sectional study 
A determinant of blood pressure is adiposity; however, there are uncertainties surrounding whether general or central adiposity is the more important determinant of blood pressure. Further, inconsistent results exist for the relationships of anthropometric measures with blood pressure and hypertension, and whether these relationships differ substantially by age and sex is unclear. We aimed to elucidate the associations of anthropometric measures of general and central adiposity with blood pressure and hypertension, and determine the effect of age and sex on these relationships.
We used cross-sectional data from the Centre for Global Health Research health check-up survey conducted during 2006–2007 of the general population in India (n = 7 601; age 18–59 years). We examined the associations of anthropometric measures (body mass index, waist circumference, hip circumference, waist-hip ratio, waist-height ratio) with blood pressure components (systolic pressure, diastolic pressure, pulse pressure, mean arterial pressure, mid-blood pressure) and hypertension within four (18–29 years, 30–39 years, 40–49 years, 50–59 years) age groups, by sex. We adjusted all analyses for education and location, with further adjustments, variously, for either a measure of central (waist circumference) or general (body mass index) adiposity.
On average, every 5 kg/m2 greater body mass index or 10 cm wider waist circumference was associated with a 5 and 4 mmHg higher systolic blood pressure, respectively. When considered separately, each anthropometric measure was strongly and positively associated with most blood pressure components in all age groups, and for both sexes. However, with few exceptions, when considered jointly (body mass index adjusted for waist circumference), the associations of body mass index with blood pressure components and hypertension were greatly diminished for both sexes, and particularly in the ≥30 years age groups. By contrast, further adjustment of waist circumference for body mass index did not materially alter the associations of waist circumference with blood pressure components and hypertension.
Our findings indicate that central adiposity, as assessed with anthropometric measures, may be a more important determinant of blood pressure and hypertension than general adiposity for adults in India.
PMCID: PMC5134088  PMID: 27905876
Age; Sex; Anthropometry; Body mass index; Waist circumference; Adiposity; Blood pressure; Hypertension; India
14.  Association of endothelin-1 and matrix metallopeptidase-9 with metabolic syndrome in middle-aged and older adults 
Metabolic syndrome (MetS) contains a cluster of cardiovascular risk factors. People with MetS are more susceptible to cardiovascular disease, diabetes mellitus, and cancer. Endothelin-1 (ET-1) and matrix metallopeptidase-9 (MMP-9) have been implicated in the development of cardiovascular diseases, diabetes mellitus and cancers. This cross-sectional study aimed to examine the association of ET-1 and MMP-9 with MetS in middle-aged and older Hong Kong Chinese adults.
149 adults aged 50 to 92 (n = 75 for non-MetS group and n = 74 for MetS group) were examined. All subjects were screened for MetS according to the diagnostic guideline of the United States National Cholesterol Education Program (NCEP) Expert Panel Adult Treatment Panel (ATP) III criteria. Serum levels of ET-1 and MMP-9 were measured. Independent t test was used to detect differences between non-MetS and MetS groups and between subjects with or without certain metabolic abnormality. The association of the serum concentration of MMP-9 and ET-1 with MetS parameters were examined by Pearson’s correlation analysis.
Serum level of ET-1 is higher in MetS-positive subjects and in subjects with high blood pressure, elevated fasting blood glucose, and central obesity. The serum concentration of MMP-9 is higher in subjects positively diagnosed with MetS and subjects with high blood pressure, elevated fasting blood glucose, low blood high-density lipoprotein-cholesterol (HDL-C), high blood triglycerides, and central obesity. Correlation analyses revealed that serum concentration of ET-1 is positively correlated to systolic blood pressure, waist circumference, fasting blood glucose, and age whereas it is negatively correlated to HDL-C. MMP-9 is positively correlated to systolic blood pressure, waist circumference, fasting blood glucose, and age whereas it is negatively correlated to HDL-C.
Serum ET-1 is higher in subjects with hypertension, hyperglycemia, central obesity or MetS. Serum MMP-9 is higher in subjects diagnosed with MetS or having either one of the MetS parameters. Both circulating levels of ET-1 and MMP-9 are correlated to systolic blood pressure, waist circumference, fasting blood glucose, HDL-C, and age. Further research is needed to fully dissect the role of ET-1 and MMP-9 in the development of cancers, diabetes and cardiovascular disease in relation to MetS.
PMCID: PMC4676096  PMID: 26692905
Metabolic syndrome; Cardiovascular disease; Diabetes mellitus; Cancer; ET-1; MMP-9
15.  The Effect of Omega-3 Fatty Acid Supplementation on the Inflammatory Response to eccentric strength exercise 
Omega-3 fatty acids (omega-3) have anti-inflammatory properties. However, it is not known if omega-3 supplementation attenuates exercise-induced inflammation. We tested the hypothesis that omega-3 supplementation reduces inflammation that is induced by eccentric arm curl exercise. Healthy adult men and women (n=11; 35 ± 10 y) performed eccentric biceps curls on two occasions, once after 14d of dietary omega-3 restriction (control trial) and again after 7d of 3,000 mg/d omega-3 supplementation (omega-3 trial). Before and 48 h after eccentric exercise, signs of inflammation was assessed by measuring soreness ratings, swelling (arm circumference and arm volume), and temperature (infrared skin sensor). Arm soreness increased (p < 0.0001) in response to eccentric exercise; the magnitude of increase in soreness was 15% less in the omega-3 trial (p = 0.004). Arm circumference increased after eccentric exercise in the control trial (p = 0.01) but not in the omega-3 trial (p = 0.15). However, there was no difference between trials (p = 0.45). Arm volume and skin temperature did not change in response to eccentric exercise in either trial. These findings suggest that omega-3 supplementation decreases soreness, as a marker of inflammation, after eccentric exercise. Based on these findings, omega-3 supplementation could provide benefits by minimizing post-exercise soreness and thereby facilitate exercise training in individuals ranging from athletes undergoing heavy conditioning to sedentary subjects or patients who are starting exercise programs or medical treatments such as physical therapy or cardiac rehabilitation.
Key pointsDietary supplementation with omega-3 fatty acids has been shown to reduce inflammation in numerous inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and Chrohn’s disease.Although strenuous exercise is known to cause acute increases in inflammation, it is not clear if omega-3 fatty acid supplementation attenuates this adverse response to exercise.Our research demonstrates that 3000 mg·d-1 omega-3 fatty acid supplementation minimizes the severe, delayed-onset muscle soreness that results from strenuous eccentric strength exercise.This information, along with a plethora of information showing that omega-3 fatty acid supplementation has other health benefits, demonstrates that a readily available over the counter nutritional supplement (i.e. omega-3 fatty acids) reduces delayed-onset soreness caused by strenuous strength exercise.This information has obvious relevance to athletic populations but also to other groups such as physical therapy patients and newly admitted cardiac rehabilitation patients, as muscle soreness, if left unchecked, can slow the progress in adapting to a new exercise program.Furthermore, as inflammation is known to be involved in the pathogenesis if numerous diseases, including heart disease, cancer, and diabetes, it is likely prudent for individuals to use inflammation-attenuating interventions, such as omega-3 supplementation, to keep inflammatory responses to physical activity at a minimum.
PMCID: PMC3737804  PMID: 24150614
Fish oil; muscle soreness; eicosapentaenoic acid; docosahexaenoic acid
16.  Association between fish and shellfish, and omega-3 PUFAs intake and CVD risk factors in middle-aged female patients with type 2 diabetes 
Nutrition Research and Practice  2015;9(5):496-502.
This study was performed to investigate the association between the dietary intake of fish and shellfish, and omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD) risk factors in the middle-aged Korean female patients with Type 2 diabetes (T2D).
A cross-sectional analysis was performed with 356 female patients (means age: 55.5 years), who were recruited from the Huh's Diabetes Clinic in Seoul, Korea between 2005 and 2011. The dietary intake was assessed by a validated semi-quantitative food frequency questionnaire and analyzed using the Computer Aided Nutritional Analysis program (CAN-Pro) version 4.0 software.
In a multiple regression analysis after the adjustment for confounding factors such as age, BMI, duration of diagnosed T2D, alcohol consumption, fiber intake, sodium intake, and total energy intake, fish and shellfish intake of the subjects was negatively associated with triglyceride and pulse wave velocity (PWV). Omega-3 PUFAs intake was negatively associated with triglyceride, systolic blood pressures, diastolic blood pressures, and PWV. The multiple logistic regression analysis with the covariates showed a significant inverse relationship between the omega-3 PUFAs consumption and prevalence of hypertriglyceridemia [OR (95% CI) for greater than the median compared to less than the median: 0.395 (0.207-0.753)].
These results suggest that the consumption of fish and shellfish, good sources of omega-3 PUFAs, may reduce the risk factors for CVD in the middle-aged female patients with T2D.
PMCID: PMC4575962  PMID: 26425279
Fish intake; Omega-3 PUFAs; CVD factors; Type 2 diabetes
17.  Effect of Omega-3 Fatty Acid on the Fatty Acid Content of the Erythrocyte Membrane and Proteinuria in Patients with Diabetic Nephropathy 
Diabetic nephropathy is the leading cause of end-stage renal disease and is associated with an increased risk of cardiovascular events. Dietary omega-3 fatty acid (FA) has cardioprotective effect and is associated with a slower deterioration of albumin excretion in patients with diabetic nephropathy. In this study, we evaluated the effect of omega-3 FA on proteinuria in diabetic nephropathy patients who are controlling blood pressure (BP) with angiotensin converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB). In addition, we identified changes in erythrocyte membrane FA contents. A total of 19 patients who were treated with ACEi or ARB for at least 6 months were treated for 12 weeks with omega-3 FA (Omacor, 3 g/day) or a control treatment (olive oil, 3 g/day). Proteinuria levels were unchanged after 12 weeks compared with baseline values in both groups. The erythrocyte membrane contents of omega-3 FA and eicosapentaenoic acid (EPA) were significantly increased, and oleic acid, arachidonic acid : EPA ratio, and omega-6 : omega-3 FA ratio were significantly decreased after 12 weeks compared with the baseline values in the omega-3 FA group. Although omega-3 FA did not appear to alter proteinuria, erythrocyte membrane FA contents, including oleic acid, were altered by omega-3 FA supplementation.
PMCID: PMC4452183  PMID: 26089878
18.  Waist circumference and risk of elevated blood pressure in children: a cross-sectional study 
BMC Public Health  2011;11:613.
Increasing childhood obesity has become a major health threat. This cross-sectional study reports associations between schoolchildren's waist circumference (WC) and risk of elevated blood pressure.
We measured height, weight, neck and waist circumference, and blood pressure in regular health examinations among children in grade 1 (ages 6-7 years) at six elementary schools in Taipei County, Taiwan. Elevated blood pressure was defined in children found to have mean systolic or diastolic blood pressure greater than or equal to the gender-, age-, and height-percentile-specific 95th-percentile blood pressure value.
All 2,334 schoolchildren were examined (response rate was 100% in the six schools). The mean of systolic and diastolic blood pressure increased as WC quartiles increased (p < 0.0001). The prevalence of elevated blood pressure for boys and girls within the fourth quartile of waist circumference was 38.9% and 26.8%, respectively. In the multivariate logistic regression analyses, the adjusted odds ratios of elevated blood pressure were 1.78 (95% confidence interval [CI] = 1.13-2.80), 2.45 (95% CI = 1.56-3.85), and 6.03 (95% CI = 3.59-10.1) for children in the second, third, and fourth waist circumference quartiles compared with the first quartile. The odds ratios for per-unit increase and per increase of standard deviation associated with elevated blood pressure were 1.14 (95% CI = 1.10-1.18) and 2.22 (95% CI = 1.76-2.78), respectively.
Elevated blood pressure in children was associated with waist circumference. Not only is waist circumference easier to measure than blood pressure, but it also provides important information on metabolic risk. Further research is needed on effective interventions to identify and monitor children with increased waist circumference to reduce metabolic and blood pressure risks.
PMCID: PMC3160994  PMID: 21810218
Children; obesity; elevated blood pressure; waist circumference
19.  Effect of Omega-3 Supplementation on Visfatin, Adiponectin, and Anthropometric Indices in Women with Polycystic Ovarian Syndrome 
Polycystic ovary syndrome (PCOS) is a multifactorial, metabolic disorder. Characteristics are chronic anovulation, polycystic ovaries and hyperandrogenism. The aim of this study was to determine the effect of omega-3 supplementation on visfatin, adiponectin, and anthropometric indices in PCOS women.
The study was a randomized double blind placebo-controlled clinical trial. It was conducted on 84 women with polycystic ovary syndrome (26.92±5.05 years, BMI=31.69 Kg/m2) who referred to the fertility and infertility research center and Shahid Sadoughi hospital in Yazd. After the examination, evaluation and para-medical assessment by obstetrician, they were recruited. They took 3 capsules of omega-3 (each one contained 180 mg EPA and 120 mg DHA) or placebo (each contained 1 g paraffin) daily for 8 weeks. Statistical analysis was paired T-test and student T-test, and a p<0.05 was considered statistically significant.
After the intervention, visfatin concentration did not change in neither groups. But, at the end of the study, the mean of adiponectin concentration increased (p<0.001) in omega-3 group. Moreover, the mean of changes in this factor was significantly different between groups (p<0.005). FSH did not change in two groups of the study. However, the mean of LH decreased about 1.74 mlU/ml in omega-3 group (p<0.005). The mean of change of LH/FSH ratio between groups was significant (p<0.05). After the intervention, prolactin did not meaningfully change in both groups.
Our results showed that 8 weeks of supplementation of omega-3 may have some beneficial effects on PCOS biochemical characteristics such as LH, LH/FSH, and adiponectin.
PMCID: PMC4819211  PMID: 27110520
Adiponectin; Fertility; FSH; LH; Obesity; Omega-3; PCOS; Visfatin
20.  Deleterious Associations of Sitting Time and Television Viewing Time With Cardiometabolic Risk Biomarkers 
Diabetes Care  2009;33(2):327-334.
We examined the associations of sitting time and television (TV) viewing time with continuously measured biomarkers of cardio-metabolic risk in Australian adults.
Waist circumference, BMI, resting blood pressure, triglycerides, HDL cholesterol, fasting and 2-h postload plasma glucose, and fasting insulin were measured in 2,761 women and 2,103 men aged ≥30 years (mean age 54 years) without clinically diagnosed diabetes from the 2004–2005 Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Multivariate linear regression analyses examined associations of self-reported sitting time and TV viewing time (hours per day) with these biomarkers, adjusting for potential confounding variables.
For both women and men, sitting time was detrimentally associated with waist circumference, BMI, systolic blood pressure, fasting triglycerides, HDL cholesterol, 2-h postload plasma glucose, and fasting insulin (all P < 0.05), but not with fasting plasma glucose and diastolic blood pressure (men only). With the exception of HDL cholesterol and systolic blood pressure in women, the associations remained significant after further adjustment for waist circumference. TV viewing time was detrimentally associated with all metabolic measures in women and all except HDL cholesterol and blood pressure in men. Only fasting insulin and glucose (men only) remained deleteriously associated with TV viewing time after adjustment for waist circumference.
In women and men, sitting time and TV viewing time were deleteriously associated with cardio-metabolic risk biomarkers, with sitting time having more consistent associations in both sexes and being independent of central adiposity. Preventive initiatives aimed at reducing sitting time should focus on both nonleisure and leisure-time domains.
PMCID: PMC2809275  PMID: 19918003
21.  A yoga intervention for type 2 diabetes risk reduction: a pilot randomized controlled trial 
Type 2 diabetes is a major health problem in many countries including India. Yoga may be an effective type 2 diabetes prevention strategy in India, particularly given its cultural familiarity.
This was a parallel, randomized controlled pilot study to collect feasibility and preliminary efficacy data on yoga for diabetes risk factors among people at high risk of diabetes. Primary outcomes included: changes in BMI, waist circumference, fasting blood glucose, postprandial blood glucose, insulin, insulin resistance, blood pressure, and cholesterol. We also looked at measures of psychological well-being including changes in depression, anxiety, positive and negative affect and perceived stress. Forty-one participants with elevated fasting blood glucose in Bangalore, India were randomized to either yoga (n = 21) or a walking control (n = 20). Participants were asked to either attend yoga classes or complete monitored walking 3–6 days per week for eight weeks. Randomization and allocation was performed using computer-generated random numbers and group assignments delivered in sealed, opaque envelopes generated by off-site study staff. Data were analyzed based on intention to treat.
This study was feasible in terms of recruitment, retention and adherence. In addition, yoga participants had significantly greater reductions in weight, waist circumference and BMI versus control (weight −0.8 ± 2.1 vs. 1.4 ± 3.6, p = 0.02; waist circumference −4.2 ± 4.8 vs. 0.7 ± 4.2, p < 0.01; BMI −0.2 ± 0.8 vs. 0.6 ± 1.6, p = 0.05). There were no between group differences in fasting blood glucose, postprandial blood glucose, insulin resistance or any other factors related to diabetes risk or psychological well-being. There were significant reductions in systolic and diastolic blood pressure, total cholesterol, anxiety, depression, negative affect and perceived stress in both the yoga intervention and walking control over the course of the study.
Among Indians with elevated fasting blood glucose, we found that participation in an 8-week yoga intervention was feasible and resulted in greater weight loss and reduction in waist circumference when compared to a walking control. Yoga offers a promising lifestyle intervention for decreasing weight-related type 2 diabetes risk factors and potentially increasing psychological well-being.
Trial registration Identified NCT00090506.
PMCID: PMC4096416  PMID: 24980650
Yoga; Prediabetes; Type 2 diabetes; India; Randomized controlled pilot
22.  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.
PMCID: PMC3111427  PMID: 21694775
23.  Effect of PUFA on patients with hypertension: A hospital based study 
Indian Heart Journal  2014;66(4):408-414.
Hypertension affects more than a quarter of the global adult population. Studies conducted worldwide suggest an overall small, yet useful, role of omega-3 PUFAs in reducing blood pressure in hypertensive patients. However there is no substantial data in this regard from population based in Middle East and Asia.
To determine the effects of (omega-3) PUFA supplementation on the blood pressure of hypertensive patient.
To identify if male and female hypertensive patients respond differently to PUFA.
To identify if response of hypertensive patients to PUFA varies with the duration of hypertension and co-existence of diabetes/dyslipidemia.
Materials and methods
This observational study was conducted among hypertensive patients visiting OPD of the Gulf Medical College Hospital, Ajman, UAE, during the period Jan–Dec 2012. A total of 100 hypertensive patients on treatment with their antihypertensive medications, 50 of whom were taking n-3 PUFA supplementation, were followed up for a period of 3 months. Comparisons were drawn between the BP recordings at the time of enrollment in the study and their follow up values 3 months after enrollment.
There was a statistically significant reduction in both the systolic and diastolic blood pressures after 3 months of PUFA therapy. The BP lowering effect of PUFA was more in males. A statistically significant reduction in BP was noted in non-diabetic patients and patients with long standing hypertension.
Findings of the study suggest that omega-3 PUFA dietary supplements augment the benefits of pharmacotherapy in hypertension.
PMCID: PMC4150041  PMID: 25173198
PUFA; Hypertension; Supplements
24.  Effects of omega-3 fatty acids on arterial stiffness in patients with hypertension: a randomized pilot study 
Omega–3 fatty acids prevent cardiovascular disease (CVD) events in patients with myocardial infarction or heart failure. Benefits in patients without overt CVD have not been demonstrated, though most studies did not use treatment doses (3.36 g) of omega-3 fatty acids. Arterial stiffness measured by pulse wave velocity (PWV) predicts CVD events independent of standard risk factors. However, no therapy has been shown to reduce PWV in a blood pressure-independent manner. We assessed the effects of esterified omega–3 fatty acids on PWV and serum markers of inflammation among patients with hypertension.
Design and methods
We performed a prospective, randomized; double-blinded pilot study of omega-3 fatty acids among 62 patients in an urban, safety net hospital. Patients received 3.36 g of omega–3 fatty acids vs. matched placebo daily for 3-months. The principal outcome measure was change in brachial-ankle PWV. Serum inflammatory markers associated with CVD risk were also assessed.
The majority (71 %) were of Latino ethnicity. After 3-months, mean change in arterial PWV among omega-3 and placebo groups was −97 cm/s vs. −33 cm/s respectively (p = 0.36 for difference, after multivariate adjustment for baseline age, systolic blood pressure, and serum adiponectin). Non-significant reductions in lipoprotein-associated phospholipase A2 (LpPLA2) mass and high sensitivity C-reactive protein (hsCRP) relative to placebo were also observed (p = 0.08, and 0.21, respectively).
High-dose omega-3 fatty acids did not reduce arterial PWV or markers of inflammation among patients within a Latino-predominant population with hypertension.
Clinical trial registration
NCT00935766, registered July 8 2009.
PMCID: PMC4668614  PMID: 26631058
Pulse wave velocity; LpPLA2; Hypertension; Latino; C-reactive protein
25.  Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: A sub analysis of the Treat to Target post authorization survey. Prospective observational, two armed study in 14,200 patients 
The metabolic syndrome is a cluster of cardiovascular risk factors leading to an increased risk for the subsequent development of diabetes and cardiovascular morbidity and mortality. Blocking the renin-angiotensin system has been shown to prevent cardiovascular disease and delay the onset of diabetes. Irbesartan is an angiotensin receptor blocker (ARB) which has been shown to possess peroxisome proliferator-activated receptor gamma (PPARγ) activating properties, and to have a favorable metabolic profile. Current discussion is whether the addition of small doses of hydrochlorothiazide changes this profile. Therefore the efficacy, safety and metabolic profile of Irbesartan either as monotherapy or in combination therapy was assessed in patients with the metabolic syndrome in a large observational cohort in primary care.
Research design and methods
Multicenter, prospective, two-armed, post authorization study over 9 months in 14,200 patients with uncontrolled hypertension with and without the metabolic syndrome (doctors' diagnosis based on the Adult Treatment Panel III criteria 2001). Blood pressure was measured sphygmomanometrically and cardiovascular risk factors making up the criteria for the metabolic syndrome were assessed.
Main outcome measures
Systolic (SBP) and diastolic (DBP) blood pressure reduction, – response, and – normalization (systolic and diastolic), changes in fasting glucose, waist circumference (abdominal obesity), serum triglycerides and HDL cholesterol as well as the proportion of patients fulfilling the criteria for the metabolic syndrome. Number and nature of adverse events (AEs).
After 9 month the use of Irbesartan in monotherapy resulted in a significant reduction of blood pressure (SBP: -26.3 ± 10.1 mmHg/DBP-13.0 ± 6.6 mmHg, both p < 0.0001) in patients with the metabolic syndrome. This was accompanied by a reduction in cardiovascular risk factors: HDL cholesterol (+3.6 ± 7.2 mg/dl in men, +3.8 ± 6.5 mg/dl in women, both p < 0.0001), serum triglycerides (-28.6 ± 52.1 mg/dl, p < 0.0001), fasting blood glucose (-8.4 ± 25.1 mg/dl, p < 0.0001) and waist circumference (-2.4 ± 11.9 cm in men, -1.2 ± 14.2 in women, both p < 0.0001) were significantly improved. Irbesartan combination therapy (12.5 mg HCTZ) in patients with the metabolic syndrome: blood pressure reduction (SBP: -27.5 ± 10.1 mmHg/DBP: -14.1 ± 6.6 mmHg, both p < 0.0001), improvement in HDL cholesterol (+4.0 ± 6.8 mg/dl in men, +3.4 ± 6.8 in women, both p < 0.0001), triglycerides (-34.1 ± 52.6 mg/dl, p < 0.0001), fasting blood glucose (-10.0 ± 24.7, p < 0.0001) and waist circumference (-3.2 ± 12.7 cm in men, -1.7 ± 14.4 in women, both p < 0.0001). Tolerability was excellent: only 0.6% of patients experienced an AE.
There was a significant improvement in blood pressure and metabolic risk factors as a result of Irbesartan treatment. There was no evidence of a difference between monotherapy and combination therapy with regard to the cardiovascular risk profile.
PMCID: PMC1853076  PMID: 17407587

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