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Effect of Weight Loss and Lifestyle Changes on Vascular Inflammatory Markers in Obese Women
A Randomized Trial
Katherine Esposito, MD;
Alessandro Pontillo, MD;
Carmen Di Palo;
Giovanni Giugliano, MD;
Mariangela Masella, MD;
Raffaele Marfella, MD, PhD;
Dario Giugliano, MD, PhD
JAMA. 2003;289:1799-1804.
ABSTRACT
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Context Obesity is an independent risk factor for cardiovascular disease, which may be mediated by increased secretion of proinflammatory cytokines by adipose tissue.
Objective To determine the effect of a program of changes in lifestyle designed to obtain a sustained reduction of body weight on markers of systemic vascular inflammation and insulin resistance.
Design and Setting Randomized single-blind trial conducted from February 1999 to February 2002 at a university hospital in Italy.
Patients One hundred twenty premenopausal obese women (body mass index  30) aged 20 to 46 years without diabetes, hypertension, or hyperlipidemia.
Interventions The 60 women randomly assigned to the intervention group received detailed advice about how to achieve a reduction of weight of 10% or more through a low-energy Mediterranean-style diet and increased physical activity. The control group (n = 60) was given general information about healthy food choices and exercise.
Main Outcome Measures Lipid and glucose intake; blood pressure; homeostatic model assessment of insulin sensitivity; and circulating levels of interleukin 6 (IL-6), interleukin 18 (IL-18), C-reactive protein (CRP), and adiponectin.
Results After 2 years, women in the intervention group consumed more foods rich in complex carbohydrates (9% corrected difference; P<.001), monounsaturated fat (2%; P = .009), and fiber (7 g/d; P<.001); had a lower ratio of omega-6 to omega-3 fatty acids (-5; P<.001); and had lower energy (-310 kcal/d; P<.001), saturated fat (-3.5%; P = .007), and cholesterol intake (-92 mg/d; P<.001) than controls. Body mass index decreased more in the intervention group than in controls (-4.2; P<.001), as did serum concentrations of IL-6 (-1.1 pg/mL; P = .009), IL-18 (-57 pg/mL; P = .02), and CRP (-1.6 mg/L; P = .008), while adiponectin levels increased significantly (2.2 µg/mL; P = .01). In multivariate analyses, changes in free fatty acids (P = .008), IL-6 (P = .02), and adiponectin (P = .007) levels were independently associated with changes in insulin sensitivity.
Conclusion In this study, a multidisciplinary program aimed to reduce body weight in obese women through lifestyle changes was associated with a reduction in markers of vascular inflammation and insulin resistance.
INTRODUCTION
The rate of obesity and the numbers of dieters are increasing in parallel.1-2 More than 54 million Americans are currently dieting, yet the epidemic of obesity continues virtually unabated with no sign of reversal.3-4 Obesity is an independent risk factor for cardiovascular disease.5 Adipocytes synthesize and secrete several cytokines, including tumor necrosis factor  ,6 interleukin 6 (IL-6),7 and adiponectin,8 the latter being one of the most abundant adipose tissue–specific adipocytokines.
Elevated levels of several proinflammatory cytokines, such as IL-6, IL-18, and tumor necrosis factor , as well as the sensitive marker of inflammation C-reactive protein (CRP), have been found associated with proxy indicators of elevated body fat (body weight and body mass index [BMI], calculated as weight in kilograms divided by the square of height in meters) and with cardiovascular disease risk factors.7, 9-12 Moreover, several proinflammatory molecules, including CRP,13 IL-6,14 and IL-18,15 have been prospectively associated with thrombotic cardiovascular events.
For the present study in obese women, we measured the serum concentrations of IL-6, IL-18, and CRP, as well as adiponectin, the novel adipocytokine with anti-inflammatory and insulin-sensitizing properties,16 and their relations with anthropometric measures and insulin resistance. We then performed a randomized controlled trial of lifestyle changes designed to obtain a sustained and long-term reduction of body weight (10% of initial weight, maintained for 2 years) for evaluating the effect of weight loss on markers of vascular inflammation and insulin resistance.
METHODS
For this trial conducted from February 1999 to February 2002, obese premenopausal women aged 20 to 46 years were recruited from the outpatient department for weight loss of the teaching hospital at the second University of Naples, Italy. Women were sedentary (<1 h/wk of physical activity), with no evidence of participation in diet reduction programs within the last 6 months, and completed a personal health and medical history questionnaire, which served as a screening tool. Exclusion criteria were type 2 diabetes mellitus or impaired glucose tolerance (plasma glucose levels of 140-200 mg/dL [7.8-11.1 mmol/L] 2 hours after a 75-g oral glucose load), hypertension (blood pressure >140/90 mm Hg), cardiovascular disease, psychiatric problems, history of alcohol abuse (intake of 500 g/wk in the last year), current smoking, and any medication use. No patient was pregnant or became pregnant during the study. The study was approved by the institutional committee of ethical practice of our institution, and all study participants gave written informed consent.
Women were individually assigned to either the intervention or control group by selection of an envelope from a pile of equal numbers of envelopes for each group (Figure 1). The nurses who scheduled the study visits did not have access to the randomization list. However, the staff members involved in the intervention were aware of the group assignment. Laboratory staff did not know the participants' group assignments.
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Figure 1. Flow of Patients Through the Trial
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Women in the control group were given general oral and written information about healthy food choices and exercise at baseline and at subsequent monthly visits, but no specific individualized programs were offered to them.
Women in the intervention group were given detailed advice about how to achieve a reduction in weight of 10% or more. The program involved education on reducing dietary calories, personal goal setting, and self-monitoring (food diaries) through a series of monthly small-group sessions. Behavioral and psychological counseling was also offered. The mean caloric intake goal was set at 1300 kcal/d for the first year and 1500 kcal/d for the second year. The recommended composition of the dietary regimen was 50% to 60% carbohydrates, 15% to 20% proteins, less than 30% total fat, less than 10% saturated fat, 10% to 15% monounsaturated fat, 5% to 8% polyunsaturated fat, and 18 g of fiber per 1000 kcal. This regimen is similar to the Mediterranean-style Step I diet, which is being considered by the American Heart Association as a possible tool to lower cardiovascular risk.17 Dietary advice was tailored to each woman on the basis of 3-day food records. These women also received individual guidance on increasing physical activity, mainly by walking, but also with swimming or aerobic ball games. Women were enrolled in the program for 24 months and had monthly sessions with the nutritionist and exercise trainer for the first year and bimonthly sessions for the second year. Compliance was assessed by attendance at the meetings and completion of the diet diaries.
Height and weight were recorded with participants wearing lightweight clothing and no shoes using a Seca 200 scale with attached stadiometer (Seca, Hamburg, Germany). Waist-hip ratio (WHR) was calculated as waist circumference in centimeters divided by hip circumference in centimeters. Twenty-four-hour nutrient intakes were calculated with food-composition tables and patients' weekly diet diaries. All women were asked to complete a 3-day food intake record and to record occupational, household, and leisure-time physical activity to assess dietary adherence and exercise activity. Foods were measured using standard measuring cups and spoons and weight-approximation diagrams.
Insulin sensitivity in the fasting state was assessed with homeostasis model assessment (HOMA) and calculated with the following formula: fasting plasma glucose (mmol/L) x fasting serum insulin (µU/mL) divided by 25, as described by Matthews et al.18 High HOMA scores denote low insulin sensitivity (insulin resistance). Assays for serum total and high-density lipoprotein cholesterol, triglyceride, and glucose levels were performed in the hospital's chemistry laboratory. Plasma free fatty acids (FFAs) were determined as previously described.19 Plasma insulin levels were assayed by radioimmunoassay (Ares, Serono, Italy).
Serum samples for cytokine and CRP levels were stored at -80°C until assayed. Serum concentrations of IL-6 and IL-18 were determined in duplicate using a highly sensitive, quantitative sandwich enzyme assay (Quantikine HS, R&D Systems, Minneapolis, Minn). The lower limit of detection was 0.7 pg/mL for both. High-sensitivity CRP was assayed by immunonephelometry on a Behring Nephelometer 2 (Dade Behring, Marburg, Germany). Plasma adiponectin was assessed using a commercially available radioimmunoassay kit (HADP-61HK, Linco Research, St Charles, Mo). In our laboratory, the normal means (and ranges) for these values, based on 80 healthy nonobese women matched to obese women for age and metabolic characteristics, are as follows: IL-6, 1.9 pg/mL (0.3-12.5 pg/mL); IL-18, 129 pg/mL (50-275 pg/mL); CRP, 1.2 mg/L (0.3-10 mg/L); and adiponectin, 8.7 µg/mL (1.6-15 µg/mL).
Data are presented as mean (SD) unless otherwise stated. Data were analyzed by intention to treat. We compared baseline data using a t test for continuous variables and a nonparametric Wilcoxon test for IL-6, IL-18, CRP, and adiponectin. We compared risk factors and nutrient intakes after 2 years using a test based on the values at the end of follow-up and a t test based on differences from baseline. Results of the analysis omitting patients lost to follow-up did not differ from that including their last available records; data are therefore shown for the analysis that includes all women. Spearman rank correlation coefficients were used to quantify the relations between metabolic variables and cytokine levels. The effects of weight loss on cytokine levels were tested by means of paired t tests on log-transformed values and a nonparametric Wilcoxon matched test. Multivariate regression analysis tested the independent association and contribution of changes in BMI, WHR, FFA, physical activity, and plasma cytokine concentrations with the dependent variable (changes in HOMA). P<.05 was considered significant. All analyses were conducted using SPSS version 9.0 (SPSS Inc, Chicago, Ill).
RESULTS
One hundred twenty women were randomly assigned to the intervention (n = 60) or control group (n = 60) (Figure 1). Because participants were carefully screened for exclusion criteria, both groups were comparable and relatively healthy (Table 1). All women were premenopausal and obese, with BMI values ranging from 30 to 49. As expected for an obese female population, serum IL-6, IL-18, and CRP levels were higher than reported in nonobese women.9-12 In contrast, adiponectin levels were significantly lower (P = .008) in the obese women in the present study compared with a group of nonobese women (n = 80) matched for age and metabolic and clinical characteristics (whose adiponectin levels were 8.7 µg/mL).
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Table 1. Clinical Characteristics of Study Participants*
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Spearman rank correlation coefficients between serum cytokine levels and metabolic variables are shown in Table 2. Univariate correlations are reported because they were affected very little by adjustment for age. Serum IL-6 levels were positively associated and adiponectin levels were negatively associated with BMI, WHR, insulin, HOMA, and FFA. To investigate which variables might account for the association between circulating IL-6 or adiponectin levels and insulin resistance, multiple regression analysis was performed. The independent variables were those significantly correlated with both IL-6 and adiponectin in univariate analysis. Only BMI (P = .03), FFA (P = .02), and HOMA (P = .04) were independently and significantly associated with IL-6 (positively) or adiponectin (negatively).
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Table 2. Correlations With IL-6, IL-18, and Adiponectin in All Obese Women (n = 120)
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After 2 years of follow-up, there were 3 dropouts in the intervention group and 5 in the control group, all of which occurred after 24 weeks of follow-up. Dropouts from the intervention group showed a decrease in body weight after 24 weeks of follow-up, suggesting that they were adhering to the lifestyle changes. Baseline data showed no important differences in nutrient intake between the 2 groups (Table 3). After 2 years, patients in the intervention group consumed a greater percentage of calories from complex carbohydrates, protein, and monounsaturated fat; had a lower ratio of omega-6 to omega-3 fatty acids; and had lower energy, saturated fat, and cholesterol intake levels than controls. The level of physical activity increased more in the intervention group (from 64 to 175 min/wk) than in the control group (from 71 to 102 min/wk [P = .009]).
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Table 3. Nutrient Indices at Entry to Study and at 2 Years*
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After 2 years, both groups had a significant decrease in body weight, BMI, WHR, blood pressure, glucose, insulin and HOMA, triglycerides, and FFA, with a larger effect in the intervention group (Table 4). High-density lipoprotein cholesterol increased more in the intervention group. Serum concentrations of IL-6, IL-18, and CRP were significantly reduced in those the intervention group compared with controls, while adiponectin levels were significantly increased (Figure 2). The magnitude and significance of the weight loss–induced difference in cytokine and CRP levels were similar when a paired t test was performed on log10-transformed values or when a nonparametric Wilcoxon matched test was used.
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Table 4. Cardiovascular Risk Factors at Baseline and at 2 Years*
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Figure 2. Serum Concentrations of Cytokines and C-Reactive Protein at Baseline and 2 Years
Data are shown as medians, interquartile ranges, and extreme values. P values are for comparisons of treatment effects between the intervention and control groups.
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In the intervention group, changes in cytokine and CRP concentrations were related to the reduction in BMI (for IL-6, r = 0.35; P = .02; for IL-18, r = 0.29; P = .04; for CRP, r = 0.41; P = .008; and for adiponectin, r = -0.31; P = .02). For evaluating the independent association of changes in HOMA with changes in serum IL-6 and adiponectin levels, a multivariate analysis was performed in which HOMA was the dependent variable and BMI, WHR, physical activity, plasma FFA, and serum IL-6 and adiponectin were the independent variables. Free fatty acids (27.6% of the variance; P = .008), IL-6 (15% of the variance; P = .02), and adiponectin (22% of the variance; P = .007) were independent predictors of HOMA and explained approximately 65% of the variability.
COMMENT
In this study, we tested the hypothesis that a multidisciplinary approach aimed at reducing body weight by 10% or more was effective at 2 years and reduced circulating levels of inflammatory markers of future cardiovascular events. The physiological rationales underlying these hypotheses are that (1) obesity is a difficult problem, such that at most, 10% of dieters manage to keep the weight off in the long term20; (2) obesity has been positively associated with insulin resistance and increased serum concentrations of vascular inflammatory markers9-10; and (3) adipose tissue has been proposed as a factor directly modulating proinflammatory and anti-inflammatory cytokine levels.6-8
In the baseline cross-sectional analysis of all 120 obese women, we observed significant associations between metabolic variables and levels of inflammatory markers. Similar to previous studies,7, 9-11 we found positive correlations among body weight, BMI, WHR, and levels of CRP, IL-6, and IL-18, suggesting that the circulating levels of these cytokines may reflect, at least in part, production by adipose tissue. Fasting serum concentrations of IL-6 were positively associated and adiponectin levels were negatively associated with all of the markers of insulin resistance measured (fasting insulin levels, HOMA, and WHR). The mechanisms whereby high IL-6 or low adiponectin levels can induce insulin resistance at the cellular level are poorly understood. However, IL-6 increases plasma FFA and fat oxidation in humans,21 whereas plasma adiponectin levels are positively associated with whole-body insulin sensitivity.22 Interestingly, there is some evidence that adiponectin may participate in fatty acid and energy homeostasis.23 It is possible that a high production of IL-6 from adipose tissue associated with low production of adiponectin may be involved in obesity-associated insulin resistance through convergent effects on increasing plasma fatty acid levels. The associations we found between FFA and IL-6 and adiponectin, both at baseline and after weight loss, seem to support this interpretation.
This study shows that weight loss can be effectively achieved in the long term by a multidisciplinary approach to lifestyle changes in obese premenopausal women. The intervention program showed improvement in the number of surrogate traditional and novel cardiovascular risk factors, which were better than those observed in controls. Our results suggest that to be successful, interventions should be multifactorial and of long duration. Otherwise, the initial efforts and enthusiasm for healthier lifestyles are eroded by external obesogenic environmental forces.24 If the lifestyles can be maintained, they will reduce the amount of weight gain and the risk of associated diseases.
The obese women we studied had yet to heed the messages about prevention of heart disease. Baseline diets in our participants contained large amounts of saturated fat, cholesterol, and refined carbohydrates and small amounts of fiber and omega-3 fatty acids. Dietary supplementation with whole grain products, legumes, fruit, vegetables, fish, and olive oil was associated with improvement of nutrient indices at 2 years (Table 3) and a substantial decrease in cardiovascular risk (Table 4) in the intervention group. Given the strict exclusion criteria, the obese women were healthy at baseline, and no cardiovascular events occurred in the 2 years of follow-up. However, diets with similar characteristics to those we used, accompanied by small weight changes, can reduce cardiac end points in high-risk patients in the first few months of follow-up.25-26
The vascular inflammatory markers that improved after 2 years of follow-up in the intervention group are linked to future thrombotic events through mechanisms of plaque destabilization. Consistent findings support a predictive role of CRP and IL-6 in different populations,27 IL-18 has been identified as an independent predictor of cardiovascular death in patients with a broad spectrum of coronary artery disease,15 and circulating levels of adiponectin are lower in patients with coronary artery disease.28 Thus, the increased cardiovascular risk of obese persons may be seen as the result, at least in part, of increased inflammatory stimuli and decreased anti-inflammatory mechanisms.
The obesity-inflammation relationship has been addressed by previous studies9-11,22, 29-30 that were characterized by limited follow-up, absence of a control group, small numbers of patients, and lack of adiponectin data, at least for nonsurgically treated obese patients.22 We show that a multidisciplinary program aimed to reduce body weight in obese women through lifestyle changes, including a low-energy Mediterranean-type diet and increased exercise, is feasible and gives sustained results over 2 years, as indicated by the significant reduction of markers of inflammation and improved insulin sensitivity. Although we cannot exclude that the change in physical activity and food intake may have contributed to the effects of weight loss, the potential benefits of the program justify its evaluation as a way to decrease cardiovascular risk in obese patients.
AUTHOR INFORMATION
Corresponding Author and Reprints: Katherine Esposito, MD, Center for Obesity Management, Department of Geriatrics and Metabolic Diseases, Policlinico Universitario, Piazza L. Miraglia, 80138 Napoli, Italy (e-mail: katherine.esposito{at}unina2.it).
Author Contributions: Study concept and design: Esposito, D. Giugliano.
Acquisition of data: Esposito, Pontillo, Di Palo, Masella, D. Giugliano.
Analysis and interpretation of data: Esposito, G. Giugliano, Marfella, D. Giugliano.
Drafting of the manuscript: Esposito, D. Giugliano.
Critical revision of the manuscript for important intellectual content: Esposito, Pontillo, Di Palo, G. Giugliano, Masella, Marfella, D. Giugliano.
Statistical expertise: Marfella, D. Giugliano.
Administrative, technical, or material support: Pontillo, Di Palo.
Study supervision: Esposito, G. Giugliano, Masella, D. Giugliano.
Author Affiliations: Center for Obesity Management, Department of Geriatrics and Metabolic Diseases (Drs Esposito and Pontillo and Ms Di Palo), Chair of Plastic and Reconstructive Surgery (Dr G. Giugliano), Department of Psychiatry (Dr Masella), and Cardiovascular Research Center (Drs Marfella and D. Giugliano), Second University of Naples, Naples, Italy.
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Circulating Levels of Inflammatory Cytokines and Risk of Colorectal Adenomas
Kim et al.
Cancer Res. 2008;68:323-328.
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Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction
Packard and Libby
Clin. Chem. 2008;54:24-38.
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Lifestyle Intervention and Adipokine Levels in Subjects at High Risk for Type 2 Diabetes: The Study on Lifestyle intervention and Impaired glucose tolerance Maastricht (SLIM)
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Diabetes Care 2007;30:3125-3127.
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Association of C-Reactive Protein with Surrogate Measures of Insulin Resistance among Nondiabetic US Adults: Findings from National Health and Nutrition Examination Survey 1999 2002
Meng et al.
Clin. Chem. 2007;53:2152-2159.
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Effects of long-term exercise and diet intervention on plasma adipokine concentrations
Rokling-Andersen et al.
Am. J. Clin. Nutr. 2007;86:1293-1301.
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Obesity-associated mouse adipose stem cell secretion of monocyte chemotactic protein-1
Zhou et al.
Am. J. Physiol. Endocrinol. Metab. 2007;293:E1153-E1158.
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C-Reactive Protein Gene Polymorphisms, C-Reactive Protein Blood Levels, and Cardiovascular Disease Risk
Hage and Szalai
J Am Coll Cardiol 2007;50:1115-1122.
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Rosiglitazone Decreases Serum Bone-Specific Alkaline Phosphatase Activity in Postmenopausal Diabetic Women
Berberoglu et al.
J. Clin. Endocrinol. Metab. 2007;92:3523-3530.
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Interleukin-18, the Metabolic Syndrome, and Subclinical Atherosclerosis: Results From the Dallas Heart Study
Zirlik et al.
Arterioscler. Thromb. Vasc. Bio. 2007;27:2043-2049.
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Cardiovascular Actions of Insulin
Muniyappa et al.
Endocr. Rev. 2007;28:463-491.
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C-Reactive Protein before and after Weight Loss in Overweight Women with and without Polycystic Ovary Syndrome
Moran et al.
J. Clin. Endocrinol. Metab. 2007;92:2944-2951.
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Lower heart rate variability is associated with higher plasma concentrations of IL-6 in type 1 diabetes
Gonzalez-Clemente et al.
Eur J Endocrinol 2007;157:31-38.
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Associations of Adiponectin with Body Fat Distribution and Insulin Sensitivity in Nondiabetic Hispanics and African-Americans
Hanley et al.
J. Clin. Endocrinol. Metab. 2007;92:2665-2671.
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Plasma Vitamin C Is Inversely Related to Body Mass Index and Waist Circumference but Not to Plasma Adiponectin in Nonsmoking Adults
Johnston et al.
J. Nutr. 2007;137:1757-1762.
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Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral, and metabolic variables
Jurimae and Jurimae
Am. J. Physiol. Endocrinol. Metab. 2007;293:E42-E47.
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Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency
Zorrilla et al.
Proc. Natl. Acad. Sci. USA 2007;104:11097-11102.
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Impact of weight change on albuminuria in the general population
Bello et al.
Nephrol Dial Transplant 2007;22:1619-1627.
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An Investigation of Hormone and Lipid Associations after Weight Loss in Women
Santosa et al.
J. Am. Coll. Nutr. 2007;26:250-258.
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Adiponectin levels in patients with intracranial atherosclerosis
Bang et al.
Neurology 2007;68:1931-1937.
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State of the Art Reviews: The Anti-Inflammatory Actions of Exercise Training
Flynn et al.
AMERICAN JOURNAL OF LIFESTYLE MEDICINE 2007;1:220-235.
ABSTRACT
Adiponectin--an adipokine with unique metabolic properties
Wiecek et al.
Nephrol Dial Transplant 2007;22:981-988.
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Challenges and Strategies in Managing Cardiometabolic Risk
Repas
JAOA: Journal of the American Osteopathic Association 2007;107:S4-S11.
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Adiponectin and cardiovascular disease: state of the art?
Szmitko et al.
Am. J. Physiol. Heart Circ. Physiol. 2007;292:H1655-H1663.
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Effect of a High-Fiber Diet vs a Fiber-Supplemented Diet on C-Reactive Protein Level
King et al.
Arch Intern Med 2007;167:502-506.
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The insulin resistance syndrome: physiological considerations
Kashyap and Defronzo
Diabetes and Vascular Disease Research 2007;4:13-19.
ABSTRACT
Exercise Reduces Resistin and Inflammatory Cytokines in Patients With Type 2 Diabetes
Kadoglou et al.
Diabetes Care 2007;30:719-721.
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Low-carbohydrate diet and coronary heart disease in women.
Esposito et al.
NEJM 2007;356:750-750.
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Adiponectin and Cardiovascular Disease: Response to Therapeutic Interventions
Han et al.
J Am Coll Cardiol 2007;49:531-538.
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Ethnicity, Insulin Resistance, and Inflammatory Adipokines in Women at High and Low Risk for Vascular Disease
Silha et al.
Diabetes Care 2007;30:286-291.
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The Effect of Weight Loss on C-Reactive Protein: A Systematic Review
Selvin et al.
Arch Intern Med 2007;167:31-39.
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Systemic lupus erythematosus and exercise
Ayan and Martin
Lupus 2007;16:5-9.
ABSTRACT
Exercise and Biomarkers for Cancer Prevention Studies
Campbell and McTiernan
J. Nutr. 2007;137:161S-169S.
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Insulin Resistance as a Determinant of Platelet Activation in Obese Women
Basili et al.
J Am Coll Cardiol 2006;48:2531-2538.
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Recreational Physical Activity and Risk of Postmenopausal Breast Cancer Based on Hormone Receptor Status
Bardia et al.
Arch Intern Med 2006;166:2478-2483.
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The Role of Insulin Resistance in Nonalcoholic Fatty Liver Disease
Utzschneider and Kahn
J. Clin. Endocrinol. Metab. 2006;91:4753-4761.
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Interrelations between fat distribution, muscle lipid content, adipocytokines, and insulin resistance: effect of moderate weight loss in older women.
Mazzali et al.
Am. J. Clin. Nutr. 2006;84:1193-1199.
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C-reactive protein and mortality in mild to moderate chronic obstructive pulmonary disease
Man et al.
Thorax 2006;61:849-853.
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Diet/Exercise Versus Pioglitazone: Effects of Insulin Sensitization with Decreasing or Increasing Fat Mass on Adipokines and Inflammatory Markers
Shadid et al.
J. Clin. Endocrinol. Metab. 2006;91:3418-3425.
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Endothelial Microparticles Correlate with Endothelial Dysfunction in Obese Women
Esposito et al.
J. Clin. Endocrinol. Metab. 2006;91:3676-3679.
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Obesity and the role of gut and adipose hormones in female reproduction
Gosman et al.
Hum Reprod Update 2006;12:585-601.
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High Urinary Calcium Excretion and Genetic Susceptibility to Hypertension and Kidney Stone Disease
Mente et al.
J. Am. Soc. Nephrol. 2006;17:2567-2575.
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Adherence to the Mediterranean dietary pattern is positively associated with plasma adiponectin concentrations in diabetic women.
Mantzoros et al.
Am. J. Clin. Nutr. 2006;84:328-335.
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Increased adiponectin receptor-1 expression in adipose tissue of impaired glucose-tolerant obese subjects during weight loss.
Kim et al.
Eur J Endocrinol 2006;155:161-165.
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A cardiologist's guide to waist management.
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Heart 2006;92:865-866.
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n-3 Fatty acids and the metabolic syndrome
Carpentier et al.
Am. J. Clin. Nutr. 2006;83:S1499-1504S.
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Weight loss reduces plasma endothelin-1 concentration in obese men.
Maeda et al.
Exp. Biol. Med. 2006;231:1044-1047.
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Bone, Body Weight, and Weight Reduction: What Are the Concerns?
Shapses and Riedt
J. Nutr. 2006;136:1453-1456.
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Endocrine responses to acute and chronic high-altitude exposure (4,300 meters): modulating effects of caloric restriction
Barnholt et al.
Am. J. Physiol. Endocrinol. Metab. 2006;290:E1078-E1088.
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Adipose tissue metabolism, diabetes and vascular disease -- lessons from in vivo studies
Summers
Diabetes and Vascular Disease Research 2006;3:12-21.
ABSTRACT
Reciprocal Relationships Between Insulin Resistance and Endothelial Dysfunction: Molecular and Pathophysiological Mechanisms
Kim et al.
Circulation 2006;113:1888-1904.
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Responses of inflammatory markers to a low-fat, high-carbohydrate diet: effects of energy intake.
Kasim-Karakas et al.
Am. J. Clin. Nutr. 2006;83:774-779.
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Effect of a 4 week physical training program on plasma concentrations of inflammatory markers in patients with abnormal glucose tolerance.
Oberbach et al.
Eur J Endocrinol 2006;154:577-585.
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Association of Educational Level with Inflammatory Markers in the Framingham Offspring Study
Loucks et al.
Am J Epidemiol 2006;163:622-628.
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Systemic monocyte chemoattractant protein-1 concentrations are independent of type 2 diabetes or parameters of obesity: results from the Cooperative Health Research in the Region of Augsburg Survey S4 (KORA S4)
Herder et al.
Eur J Endocrinol 2006;154:311-317.
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A Single Factor Underlies the Metabolic Syndrome: A confirmatory factor analysis
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Diabetes Care 2006;29:113-122.
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Inflammatory Markers and the Metabolic Syndrome: Insights From Therapeutic Interventions
Koh et al.
J Am Coll Cardiol 2005;46:1978-1985.
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C-Reactive Protein and Risk of Cardiovascular Disease in Men and Women From the Framingham Heart Study
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Arch Intern Med 2005;165:2473-2478.
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What is the relationship between risk factor reduction and degree of weight loss?
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Eur Heart J Suppl 2005;7:L21-L26.
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Effect of exercise training on plasma levels of C-reactive protein in healthy adults: the HERITAGE Family Study
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Eur Heart J 2005;26:2018-2025.
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Exercise training: only if needed?
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Eur Heart J 2005;26:1939-1941.
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Association between Circulating Adiponectin and Interleukin-10 Levels in Android Obesity: Effects of Weight Loss
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J. Clin. Endocrinol. Metab. 2005;90:5876-5879.
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Elevated Levels of Interleukin-18 Predict the Development of Type 2 Diabetes: Results From the MONICA/KORA Augsburg Study, 1984-2002
Thorand et al.
Diabetes 2005;54:2932-2938.
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Adiponectin and high-density lipoprotein: a metabolic association through thick and thin
Toth
Eur Heart J 2005;26:1579-1581.
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Fat as an endocrine organ: influence of exercise
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J. Appl. Physiol. 2005;99:757-764.
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Effect of sucrose on inflammatory markers in overweight humans
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Am. J. Clin. Nutr. 2005;82:421-427.
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Reduction of Macrophage Infiltration and Chemoattractant Gene Expression Changes in White Adipose Tissue of Morbidly Obese Subjects After Surgery-Induced Weight Loss
Cancello et al.
Diabetes 2005;54:2277-2286.
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Association of Adiponectin Level and Variants in the Adiponectin Gene with Glucose Metabolism, Energy Expenditure, and Cytokines in Offspring of Type 2 Diabetic Patients
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J. Clin. Endocrinol. Metab. 2005;90:4216-4223.
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