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1.
Ann Intern Med ; 151(5): 306-14, 2009 Sep 01.
Article in English | MEDLINE | ID: mdl-19721018

ABSTRACT

BACKGROUND: Low-carbohydrate and low-fat calorie-restricted diets are recommended for weight loss in overweight and obese people with type 2 diabetes. OBJECTIVE: To compare the effects of a low-carbohydrate Mediterranean-style or a low-fat diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes. DESIGN: Single-center, randomized trial. Randomization was computer-generated and unstratified. Allocation was concealed in sealed study folders held in a central, secure location until participants gave informed consent. Participants and investigators were aware of treatment assignment, and assessors of the primary outcome were blinded. SETTING: Teaching hospital in Naples, Italy. PATIENTS: 215 overweight people with newly diagnosed type 2 diabetes who were never treated with antihyperglycemic drugs and had hemoglobin A(1c) (HbA(1c)) levels less than 11%. INTERVENTION: Mediterranean-style diet (<50% of daily calories from carbohydrates) (n = 108) or a low-fat diet (<30% of daily calories from fat) (n = 107). MEASUREMENTS: Start of antihyperglycemic drug therapy, defined by protocol as indicated for follow-up HbA(1c) level greater than 7% (primary outcome), and changes in weight, glycemic control, and coronary risk factors (secondary outcomes). RESULTS: After 4 years, 44% of patients in the Mediterranean-style diet group and 70% in the low-fat diet group required treatment (absolute difference, -26.0 percentage points [95% CI, -31.1 to -20.1 percentage points]; hazard ratio, 0.63 [CI, 0.51 to 0.86]; hazard ratio adjusted for weight change, 0.70 [CI, 0.59 to 0.90]; P < 0.001). Participants assigned to the Mediterranean-style diet lost more weight and experienced greater improvements in some glycemic control and coronary risk measures than did those assigned to the low-fat diet. LIMITATIONS: Investigators responsible for initiating drug therapy were not blinded to treatment assignment. Dietary intake was self-reported. CONCLUSION: Compared with a low-fat diet, a low-carbohydrate, Mediterranean-style diet led to more favorable changes in glycemic control and coronary risk factors and delayed the need for antihyperglycemic drug therapy in overweight patients with newly diagnosed type 2 diabetes. PRIMARY FUNDING SOURCE: Second University of Naples.


Subject(s)
Diabetes Mellitus, Type 2/diet therapy , Diet, Carbohydrate-Restricted , Diet, Mediterranean , Overweight/diet therapy , Adult , Aged , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diet, Fat-Restricted , Exercise , Female , Follow-Up Studies , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/therapeutic use , Male , Middle Aged , Obesity/complications , Obesity/diet therapy , Overweight/complications , Risk Factors , Weight Loss
2.
J Sex Med ; 6(6): 1696-1703, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19453904

ABSTRACT

INTRODUCTION: No reported studies exist assessing the relationship between sexual function and hyperlipidemia in women. AIM: In this study, we assessed the domains of sexual function in a representative sample of sexually active premenopausal women with hyperlipidemia, but without cardiovascular disease, as compared with an age-matched female population without hyperlipidemia. METHODS: To be enrolled in the study, women had to meet at least one of the following criteria for the diagnosis of hyperlipidemia: low-density lipoprotein (LDL) cholesterol levels >160 mg/dL; high-density lipoprotein (HDL) cholesterol levels <50 mg/dL; or triglyceride levels >150 mg/dL. Lipid parameters were assessed and verified on blood taken at least twice in the hospital during the screening phase. Four hundred forty-one premenopausal women with hyperlipidemia were compared with 115 age-matched premenopausal women without hyperlipidemia. MAIN OUTCOME MEASURES: We used the Female Sexual Function Index (FSFI) for assessing the key dimensions of female sexual function. RESULTS: The two groups were well matched for age and smoking prevalence. Compared with women of the control group, women with hyperlipidemia had reduced mean global FSFI score (22.8 +/- 6.8 vs. 29.4 +/- 4.9, P < 0.001). Individual analysis of the different domains showed that women with hyperlipidemia reported significantly lower arousal, orgasm, lubrication, and satisfaction scores than control women. Based on the total FSFI score, 51% of women with hyperlipidemia had scores of 26 or less, indicating sexual dysfunction, as compared with 21% of women without hyperlipidemia (P < 0.001). Based on a more conservative analysis including women under the lower quartile of the distribution of FSFI score, 32% of women with hyperlipidemia had scores of 23 or less, as compared with 9% of women without hyperlipidemia (P < 0.001). Multiple regression analysis identified age, body mass index, HDL-cholesterol and triglycerides as independent predictors of FSFI score. CONCLUSIONS: Women with hyperlipidemia have significantly lower FSFI-domain scores as compared with age-matched women without hyperlipidemia. HDL cholesterol and triglyceride levels were independently associated with the FSFI score.


Subject(s)
Hyperlipidemias/epidemiology , Premenopause/physiology , Sexual Dysfunctions, Psychological/epidemiology , Adolescent , Adult , Aged , Body Mass Index , Cholesterol, LDL/blood , Female , Humans , Hyperlipidemias/blood , Middle Aged , Prevalence , Severity of Illness Index , Sexual Dysfunctions, Psychological/diagnosis , Smoking/epidemiology , Surveys and Questionnaires , Triglycerides/blood , Young Adult
3.
J Biomed Biotechnol ; 2009: 126917, 2009.
Article in English | MEDLINE | ID: mdl-19125195

ABSTRACT

Peroxisome proliferator-activated receptor gamma polymorphisms have been widely associated with type 2 diabetes, although their role in the pathogenesis of vascular complications is not yet demonstrated. In this study, a cohort of 211 type 2 diabetes, 205 obese, and 254 control individuals was genotyped for Pro12Ala, C1431T, C-2821T polymorphisms, and for a newly identified polymorphism (A-2819G). The above-mentioned polymorphisms were analyzed by gene-specific PCR and direct sequencing of all samples. A significant difference was found for -2819G frequency when patients with type 2 diabetes-particularly diabetic women with the proliferative retinopathy-were compared with healthy control individuals. In conclusion, we identified a novel polymorphism, A-2819G, in PPARG gene, and we found it to be associated with type 2 diabetes and proliferative retinopathy in diabetic females. In the analyzed population, this variant represents a genetic risk factor for developing the diabetic retinopathy, whereas Pro12Ala and C1431T do not.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Diabetic Retinopathy/genetics , PPAR gamma/genetics , Polymorphism, Single Nucleotide , Aged , Body Mass Index , Chi-Square Distribution , Cohort Studies , Female , Gene Expression Regulation , Glycated Hemoglobin/genetics , Humans , Italy , Male , Middle Aged , Obesity/genetics , Regression Analysis , Regulatory Sequences, Nucleic Acid
4.
J Sex Med ; 6(1): 107-14, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19170841

ABSTRACT

INTRODUCTION: Bone marrow-derived endothelial progenitor cells (EPCs) circulate in the peripheral blood and are involved in endothelial homeostasis and repair. AIM: The aim of this study was to assess the circulating levels of different EPC phenotypes in overweight men with or without erectile dysfunction (ED). As endothelial dysfunction is considered a necessary link with ED, endothelium-dependent vasodilation and its relation with EPCs were also investigated. METHODS: We studied 30, otherwise healthy, overweight subjects with symptomatic ED for at least 6 months, and 30 age- and weight-matched subjects without ED. Erectile function was assessed by completing the International Index of Erectile Function (IIEF-5), which consists of items 5, 15, 4, 2, and 7 from the full-scale IIEF-15. MAIN OUTCOME MEASURES: Seven subpopulations of EPCs were determined by flow cytometry on the basis of the surface expression of CD34, CD133, and KDR antigens: CD34(+), CD133(+), KDR(+), CD34(+)CD133(+), CD34(+)KDR(+), CD133(+)KDR(+), and CD34(+)CD133(+)KDR(+). Endothelium-dependent flow-mediated dilation (FMD) was evaluated in the right brachial artery with a high-resolution ultrasound machine following reactive hyperemia. RESULTS: CD34(+)KDR(+) cell count was significantly lower in men with ED as compared with men without ED (63.1 +/- 4 vs. 92.4 +/- 6 cells/10(6) events, mean +/- standard error, P < 0.01). There was a significant direct correlation between circulating CD34(+)KDR(+) cells and the IIEF score (r = 0.44; P = 0.01): men with the severe form of ED presented the lowest level of circulating EPC CD34(+)KDR(+) cells. No significant correlation was found between the circulating levels of the other EPC phenotypes and the IIEF score. There was a significant correlation between CD34(+)KDR(+) cell count and FMD (r = 0.45; P = 0.01), but not between FMD and the other phenotypes. CONCLUSIONS: Circulating levels of CD34(+)KDR(+) EPC are reduced in overweight subjects with ED and correlate with the severity of ED. Other EPC phenotypes are not related to ED, suggesting that the CD34(+)KDR(+) phenotype of EPCs may be preferred in future studies.


Subject(s)
Antigens, CD34/immunology , Endothelium, Vascular/immunology , Endothelium, Vascular/physiopathology , Erectile Dysfunction/epidemiology , Erectile Dysfunction/immunology , Obesity/epidemiology , Overweight , Stem Cells/immunology , Vascular Endothelial Growth Factor Receptor-2/immunology , Anthropometry , Body Mass Index , Humans , Male , Middle Aged , Phenotype
5.
J Sex Med ; 6(1): 243-50, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19170853

ABSTRACT

INTRODUCTION: Limited data are available supporting the notion that treatment of lifestyle risk factors may improve erectile dysfunction (ED). AIM: In the present study, we analyzed the effect of a program of changing in lifestyle designed to improve erectile function in subjects with ED or at increasing risk for ED. METHODS: Men were identified in our database of subjects participating in randomized controlled trials evaluating the effect of lifestyle changes. A total of 209 subjects were randomly assigned to one of the two treatment groups. The 104 men randomly assigned to the intervention program received detailed advice about how to reduce body weight, improve quality of diet, and increase physical activity. The 105 subjects in the control group were given general information about healthy food choices and general guidance on increasing their level of physical activity. MAIN OUTCOME MEASURES: Changes in erectile function score (International Index of Erectile Function-5 [IIEF-5]; items 5, 15, 4, 2, and 7 from the full-scale IIEF-15) and dependence of the restoration of erectile function on the changes in lifestyle that were achieved. RESULTS: Erectile function score improved in the intervention group. At baseline, 35 subjects in the intervention group and 38 subjects in the control group had normal erectile function (34% and 36%, respectively). After 2 years, these figures were 58 subjects in the intervention group and 40 subjects in the control group, respectively (56% and 38%, P = 0.015). There was a strong correlation between the success score and restoration of erectile function. CONCLUSIONS: It is possible to achieve an improvement of erectile function in men at risk by means of nonpharmacological intervention aiming at weight loss and increasing physical activity.


Subject(s)
Erectile Dysfunction/epidemiology , Erectile Dysfunction/psychology , Life Change Events , Life Style , Body Mass Index , Body Weight , Diet , Erectile Dysfunction/diagnosis , Humans , Male , Middle Aged , Motor Activity , Surveys and Questionnaires , Weight Loss
6.
Curr Atheroscler Rep ; 10(6): 523-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18937901

ABSTRACT

Recent changes in lifestyle, including physical inactivity and unhealthy diets, are likely to have played an important role in the global epidemic of obesity, type 2 diabetes, and metabolic syndrome. Implementation of a healthier lifestyle, with an increase in physical activity and a reduction of body weight, based on the regulation of calories and fat intake, are the basis for the prevention and treatment of both type 2 diabetes and metabolic syndrome. Intervention studies based on changes in lifestyle in individuals at risk found that diabetes incidence was reduced by 42% to 63%. Similarly, intensive lifestyle changes in patients with the metabolic syndrome have been shown to reduce the prevalence of the syndrome by 20% to 48%. Reduction of body weight, improvement of the quality of diet, and promotion of physical activity are the main approaches to prevent and treat patients with type 2 diabetes or metabolic syndrome.


Subject(s)
Diabetes Mellitus, Type 2/therapy , Life Style , Metabolic Syndrome/therapy , Humans
7.
Ann Intern Med ; 149(8): 531-9, 2008 Oct 21.
Article in English | MEDLINE | ID: mdl-18936501

ABSTRACT

BACKGROUND: Injection of long-acting insulin at bedtime is a common therapeutic approach for patients with type 2 diabetes that is poorly controlled with oral regimens. Neutral protamine lispro (NPL) insulin has demonstrated better glycemic control and similar incidence of hypoglycemic events than that of neutral protamine Hagedorn insulin. OBJECTIVE: To compare the clinical efficacy and safety of bedtime NPL insulin or insulin glargine in patients with type 2 diabetes who had suboptimal glycemic control while receiving stable doses of metformin and sulfonylurea. DESIGN: Open-label, randomized trial. SETTING: Teaching hospital (Azienda Ospedaliera Universitaria, Second University of Naples), Naples, Italy. PATIENTS: 116 adults receiving stable doses of metformin plus sulfonylurea for longer than 90 days with hemoglobin A(1c) (HbA(1c)) levels of 7.5% to 10% and fasting plasma glucose levels of 6.7 mmol/L or greater (> or =120 mg/dL). INTERVENTION: 10 IU of NPL insulin or insulin glargine injected subcutaneously at bedtime with weekly dose titrations to target fasting glucose levels less than 5.6 mmol/L (<100 mg/dL) in addition to stable oral regimens. Patients receiving nighttime sulfonylurea before the study were switched to metformin. MEASUREMENTS: The primary outcome was change in HbA(1c) levels from baseline to week 36. Secondary outcomes were HbA(1c) levels less than 7%, self-reported hypoglycemic episodes, insulin dose, self-monitored glucose level, and body weight. Twenty patients in each group had continuous glucose monitoring for 3 consecutive days before adding insulin and at week 36. RESULTS: Improvement in HbA(1c) levels was similar in both groups (1.83% and 1.89% for NPL and glargine, respectively). The difference between the groups was 0.06 percentage point (95% CI, -0.1 to 0.15 percentage points). Secondary outcomes did not differ between groups. Hemoglobin A(1c) levels less than 7% occurred in 62% of patients receiving NPL and 64% of patients receiving glargine (difference, 2.0 percentage points [CI, -1.1 to 5.0 percentage points]). Fasting plasma glucose levels less than 5.6 mmol/L (<100 mg/dL) occurred in 40% of patients receiving NPL and 41% of patients receiving glargine (difference, 1.0 percentage point [CI, -0.9 to 3.0 percentage points]). Any hypoglycemic event occurred in 74% of patients receiving NPL and 67% of patients receiving glargine (difference, 7 percentage points [CI, -5 to 13 percentage points]). Continuous glucose level monitoring in the patients who had this measurement did not differ statistically. LIMITATION: The study was not blinded, had limited power to detect differences in hypoglycemic events, and did not obtain continuous glucose level monitoring for all patients. CONCLUSION: Similar glycemic control occurred with the addition of NPL or glargine insulin to oral regimens in patients with poorly controlled type 2 diabetes. Hypoglycemia was similar in the 2 groups, but sample size limited the ability to make a definite safety assessment.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin/analogs & derivatives , Protamines/administration & dosage , Administration, Oral , Adult , Aged , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Drug Therapy, Combination , Female , Glycated Hemoglobin/metabolism , Humans , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Injections, Subcutaneous , Insulin/administration & dosage , Insulin/adverse effects , Insulin Glargine , Insulin, Long-Acting , Male , Metformin/administration & dosage , Metformin/adverse effects , Middle Aged , Protamines/adverse effects , Sulfonylurea Compounds/administration & dosage , Sulfonylurea Compounds/adverse effects , Weight Gain
8.
J Sex Med ; 5(6): 1436-42, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18410304

ABSTRACT

INTRODUCTION: Endothelial microparticles (EMPs) may play a role as biomarkers of vascular injury. EMPs are higher in men with diabetes diabetic men with erectile dysfunction (ED) than in nondiabetic potent men. AIM: The aim of this study was to quantize different phenotypic circulating EMP levels among diabetic and nondiabetic patients with ED, and to determine whether EMPs are released as a result of activation or apoptosis. METHODS: We studied 30 type 2 diabetic and 24 nondiabetic subjects with symptomatic ED from at least 6 months, and 20 nondiabetic men without ED matched for age and weight with diabetic and nondiabetic subjects. Erectile function was assessed by completing the International Index of Erectile Function (IEEF)-5, which consists of Items 5, 15, 4, 2, and 7 from the full-scale IIEF-15. A score of 21 or less indicates the presence of ED. MAIN OUTCOME MEASURES: EMP levels in plasma were quantified by flow cytometry. Markers for apoptosis (platelet/endothelial cell adhesion molecule 1/CD31 antigen) and activation (E-selectin/CD62E antigen) were compared. Endothelium-dependent flow-mediated dilation (FMD) was evaluated in the right brachial artery with a high-resolution ultrasound machine following reactive hyperemia. RESULTS: Diabetic patients were found to have the highest levels of EMP31+; diabetic and nondiabetic men with ED were found to have significantly higher levels of EMP62+ than nondiabetic men without ED. The EMP62/EMP31 ratio, an index of endothelial activation (high ratio) or apoptosis (low ratio), was lowest in diabetic men with ED (0.20). In the whole group of 54 men with ED (diabetic and nondiabetic), there was an inverse correlation between FMD and the number of circulating EMPs (P < 0.05). CONCLUSIONS: The presence of diabetes in subjects with ED is associated with a different pattern of endothelial cell injury. The phenotypic assessment of EMPs in diabetic patients with ED is consistent with increased apoptotic activity.


Subject(s)
Diabetes Mellitus/blood , Endothelial Cells/pathology , Endothelium, Vascular/pathology , Erectile Dysfunction/blood , Apoptosis , Biomarkers/blood , Blood Flow Velocity , Brachial Artery/diagnostic imaging , Case-Control Studies , Flow Cytometry , Humans , Male , Middle Aged , Phenotype , Ultrasonography
9.
J Clin Endocrinol Metab ; 93(4): 1345-50, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18198229

ABSTRACT

CONTEXT: Two-hour postprandial hyperglycemia is related to chronic complications of diabetes and is currently used in the international guidelines to drive the therapy. OBJECTIVE: Our objective was to assess the size and timing of post-meal glucose peaks in the everyday life of type 2 diabetic patients and the relationship with carotid atherosclerosis. DESIGN, SETTING, AND PATIENTS: This was an observational study performed in 644 outpatients with type 2 diabetes attending diabetes clinics located in the area of the Campania County, South Italy, who provided complete home blood glucose profiles and centralized carotid intima-media thickness (CIMT) assessment. The study was conducted from 2001-2005. MAIN OUTCOME MEASURES: Incremental glucose peak (IGP) was the maximal incremental increase in blood glucose obtained at any point after the meal. CIMT was assessed by carotid sonography. RESULTS: The level of glycosylated hemoglobin and CIMT progressively increased across quintiles of IGP (P for trend = 0.01 for both). In univariate analysis, all examined glycemic parameters were significantly correlated with CIMT. IGP (r = 0.40; P = 0.006) showed the strongest correlation with CIMT, which remained significant in multiple linear regression analysis (R(2) = 0.26; P = 0.01). IGP was associated with a significant increase of CIMT in tertiles of glycosylated hemoglobin. IGP occurred within 1 h from the start of the meal in 95% of the entire diabetic population. CONCLUSION: IGPs are frequent in the everyday life of patients with type 2 diabetes, occur for most (95%) within 1 h after meal, timing of IGPs is not influenced by treatment (diet or drugs), and IGPs correlate with CIMT.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 2/metabolism , Postprandial Period , Tunica Intima/pathology , Tunica Media/pathology , Aged , Diabetes Mellitus, Type 2/pathology , Female , Glycated Hemoglobin/analysis , Humans , Linear Models , Male , Middle Aged , Reproducibility of Results
10.
Mol Nutr Food Res ; 51(10): 1268-74, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17879992

ABSTRACT

The metabolic syndrome (also referred to as syndrome X or the insulin resistance syndrome) has emerged as an important cluster of risk factors for atherosclerotic disease. Patients with the syndrome also are at increased risk for developing type 2 diabetes mellitus. Common features are central (abdominal) obesity, insulin resistance, hypertension, and dyslipidemia. Weight reduction deserves first priority in individuals with abdominal obesity and the metabolic syndrome. Both weight reduction and maintenance of a lower weight are best achieved by a combination of reduced caloric intake and increased physical activity. Dietary patterns close to the Mediterranean diet and rich in fruit and vegetables, and high in monounsaturated fats are negatively associated with features of the metabolic syndrome. Some recent studies dealing specifically with the effect of interventions on the resolution of the metabolic syndrome have demonstrated a 25% net reduction in the prevalence of the syndrome following lifestyle changes mainly based on nutritional recommendations. Similar rates of resolution have been obtained with drugs, such as rosiglitazone and rimonabant. The favourable benefit/hazard ratio makes Mediterranean-style diets particularly promising to reduce the cardiovascular burden associated with the metabolic syndrome.


Subject(s)
Diet, Mediterranean , Metabolic Syndrome , Diet, Atherogenic , Exercise , Humans , Inflammation , Metabolic Syndrome/diagnosis , Metabolic Syndrome/prevention & control , Risk Factors
11.
J Sex Med ; 4(5): 1367-72, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17680785

ABSTRACT

INTRODUCTION: Female sexual dysfunction (FSD) is a significant public health problem. There are no reported studies assessing the relation between sexual function and neuropathy in women, except for diabetes mellitus. AIM: The aim of this study was to explore the correlations between peripheral and autonomic neuropathy, and Female Sexual Function Index (FSFI) among nondiabetic women with or without FSD. METHODS: During a 6-month period, women were screened among outpatients seeking routine weight loss help. Cases were women, either pre- or postmenopausal, with abnormal values of FSFI score; controls were women from the same population with normal values of FSFI score, matched with cases for age and menopausal status. The total score range was 2-36; a score of 23 or lower indicated sexual dysfunction. The tool was administered during the follicular (days 5-8) phase of the menstrual cycle. MAIN OUTCOME MEASURES: The assessment of peripheral neuropathy was based on the quantitative sensory examination using the vibratory, thermal, and pain sensory thresholds. The assessment of autonomic neuropathy was based on cardiovascular reflex tests (deep breathing and squatting). RESULTS: The results of the quantitative sensory testing examination showed pathological changes in about 20% of women with FSD; the tests were abnormal in about 5% of women in the group without FSD. The percentage of women with abnormalities of autonomic cardiovascular tests was higher in the group with FSD compared with the group without FSD. CONCLUSIONS: Our results suggest an involvement of both somatic and autonomic nerve fibers in nondiabetic women with FSD.


Subject(s)
Autonomic Nervous System Diseases/etiology , Peripheral Nervous System Diseases/etiology , Sexual Dysfunction, Physiological/complications , Somatosensory Disorders/etiology , Adult , Autonomic Nervous System Diseases/diagnosis , Chi-Square Distribution , Diabetes Mellitus, Type 2/complications , Female , Humans , Middle Aged , Pain Measurement/methods , Peripheral Nervous System Diseases/diagnosis , Reproducibility of Results , Sexual Dysfunction, Physiological/psychology , Somatosensory Disorders/diagnosis , Surveys and Questionnaires , United States , Women's Health
13.
Nutr Metab Cardiovasc Dis ; 17(4): 274-9, 2007 May.
Article in English | MEDLINE | ID: mdl-17134952

ABSTRACT

BACKGROUND AND AIMS: A single high-fat meal may induce endothelial activation and dysfunction in both normal subjects and in patients with type 2 diabetes. The aim of this study was to assess the effect of a high-fat meal on endothelial function in patients with the metabolic syndrome. METHODS AND RESULTS: Twenty-five patients with the metabolic syndrome (ATP III criteria) were matched for sex, age and body mass index with 25 subjects without the metabolic syndrome. All subjects ate under supervision a high fat meal (760 calories) with 59% energy from fat, 12% energy from protein and 29% energy from carbohydrates. Compared with the control group, subjects with the metabolic syndrome had reduced endothelial function, as assessed with the l-arginine test, and higher circulating levels of TNF-alpha. Following the high-fat meal, both triglyceride and TNF-alpha levels increased more in subjects with the metabolic syndrome than in subjects without, while endothelial function decreased more in subjects with the metabolic syndrome. There was a significant relation between increases in TNF-alpha levels and decreases in endothelial function score in subjects with the metabolic syndrome (r=-0.39, P=0.03). CONCLUSION: TNF-alpha levels are increased in subjects with the metabolic syndrome; moreover, a high-fat meal produces further increase in its levels associated with endothelial dysfunction.


Subject(s)
Dietary Fats/administration & dosage , Endothelial Cells/physiology , Metabolic Syndrome/physiopathology , Tumor Necrosis Factor-alpha/physiology , Adult , Female , Humans , Male , Metabolic Syndrome/blood , Triglycerides/blood , Tumor Necrosis Factor-alpha/blood
16.
J Clin Endocrinol Metab ; 91(9): 3676-9, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16822816

ABSTRACT

CONTEXT: Cell-derived microparticles are supposed to be involved in atherogenesis. OBJECTIVE: This study aimed to evaluate circulating microparticles in obese women and their relation with anthropometric measures and endothelial dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Forty-one obese [body mass index (BMI) > 30 kg/m(2)] women and 40 normal weight (BMI < 25 kg/m(2)) age-matched women were studied. Flow cytometry was used to assess microparticles by quantification of circulating endothelial microparticles (EMP, CD31+/CD42b-) and platelet microparticles (PMP, CD31+/CD42b+) in peripheral blood; endothelium-dependent flow-mediated vasodilation (FMD) was evaluated in the right brachial artery after reactive hyperemia. RESULTS: Compared with lean women, obese women presented significantly higher numbers of EMP and PMP, and reduced FMD. BMI did not correlate with either EMP (r = 0.02, P = 0.9) or PMP (r = -0.07, P = 0.645), whereas waist-to-hip ratio (WHR) showed significant correlation with both microparticles (r = 0.699, P < 0.001; r = 0.373, P = 0.016, respectively). Both EMP and PMP counts positively correlated with impairment of FMD in obese women. Multivariate analysis correcting for age, anthropometric indices, lipid parameters, and PMP identified EMP as the only independent predictor for impaired endothelial-dependent vasodilation (P = 0.003). CONCLUSIONS: EMP are elevated in obese women and independently involved in the pathogenesis of endothelial dysfunction. WHR is the anthropometric measure more closely related to EMP and endothelial dysfunction.


Subject(s)
Endothelial Cells/pathology , Endothelium/physiopathology , Obesity/blood , Adult , Body Mass Index , Brachial Artery/physiopathology , Female , Humans , Middle Aged , Nitroglycerin/pharmacology , Obesity/physiopathology , Vasodilation/physiology , Vasodilator Agents/pharmacology , Waist-Hip Ratio
18.
Diabetes Care ; 29(5): 1071-6, 2006 May.
Article in English | MEDLINE | ID: mdl-16644639

ABSTRACT

OBJECTIVE: The aim of this study was to assess the effect of rosiglitazone on endothelial function and inflammatory markers in patients with the metabolic syndrome. RESEARCH DESIGN AND METHODS: This was a randomized, double-blind, controlled clinical trial. One hundred subjects (54 men and 46 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III, were followed for 12 months after random assignment to rosiglitazone (4 mg/day) or placebo. Primary end points were flow-mediated dilation and high-sensitivity C-reactive protein (hs-CRP) levels; secondary end points were lipid and glucose parameters, homeostasis model assessment (HOMA) of insulin sensitivity, endothelial function score, and circulating levels of interleukin (IL)-6, IL-18, and adiponectin. RESULTS: Compared with 60 control subjects matched for age and sex, patients with the metabolic syndrome had decreased endothelial function, raised concentrations of inflammatory markers, and reduced insulin sensitivity. After 12 months, subjects with the metabolic syndrome receiving rosiglitazone showed improved flow-mediated vasodilation (4.2%, P < 0.001) and reduced hs-CRP levels (-0.7 mg/dl, P = 0.04), compared with the placebo group. Moreover, HOMA (-0.8, P = 0.01) and serum concentrations of IL-6 (-0.5 pg/ml, P = 0.045) and IL-18 (-31 pg/ml, P = 0.036) were significantly reduced in subjects receiving rosiglitazone, whereas adiponectin levels showed a significant increment (2.3 microg/ml, P = 0.02). High-density lipoprotein-cholesterol levels increased more and triglyceride levels decreased more in the rosiglitazone group compared with the placebo group. At 1 year of follow-up, 30 subjects receiving rosiglitazone still had features of the metabolic syndrome, compared with 45 subjects receiving placebo (P < 0.001). CONCLUSIONS: Rosiglitazone might be effective in reducing the prevalence of the metabolic syndrome.


Subject(s)
Endothelium, Vascular/physiopathology , Hypoglycemic Agents/therapeutic use , Inflammation/physiopathology , Metabolic Syndrome/drug therapy , Metabolic Syndrome/physiopathology , Thiazolidinediones/therapeutic use , Adult , Blood Glucose/analysis , Blood Pressure , Body Size , Double-Blind Method , Female , Humans , Hypoglycemic Agents/pharmacology , Insulin/blood , Lipids/blood , Male , Middle Aged , Rosiglitazone , Thiazolidinediones/pharmacology
19.
Public Health Nutr ; 9(8A): 1073-6, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17378943

ABSTRACT

OBJECTIVES: To discuss present knowledge about the relation between adipose tissue, inflammation and the Mediterranean-style diet. DESIGN: Review of the literature and personal perspectives. SETTING AND RESULTS: Recent studies indicate that adipose tissue is an endocrine organ producing numerous proteins, collectively referred to as adipokines, with broad biological activity, which play an important autocrine role in obesity-associated complications. Adipose tissue in general and visceral fat in particular are thought to be key regulators of inflammation which is heavily involved in the onset and development of atherothrombotic disease. Moreover, chronic inflammation may also represent a triggering factor in the origin of the metabolic syndrome and type 2 diabetes mellitus. An increased release of proinflammatory adipokines from the visceral adipose tissue, associated with a reduced secretion of anti-inflammatory adipokines and cytokines, could determine a low-grade chronic inflammatory state which might play a role in the future development of the metabolic syndrome, diabetes and atherosclerosis through both insulin resistance and endothelial dysfunction. Interventions aimed at decreasing weight loss and improving adherence to a Mediterranean-style diet in people with obesity or metabolic syndrome decrease the inflammatory milieu and ameliorate both insulin resistance and endothelial dysfunction. CONCLUSIONS: Appropriate dietary patterns, as those associated with the eating model of Mediterranean-type diets, represent therapeutic strategies to reduce inflammation and the associated metabolic and cardiovascular risk.


Subject(s)
Diet, Mediterranean , Endothelium, Vascular/pathology , Inflammation/diet therapy , Obesity/diet therapy , Adipocytes/metabolism , Adipose Tissue/metabolism , Biomarkers , Cytokines/metabolism , Humans , Inflammation/metabolism , Insulin Resistance , Obesity/metabolism
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