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AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification. METHODS: Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote. RESULTS: The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m2 and < 40 kg/m2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative. CONCLUSION: The present GL is directed to all physicians addressing people with obesity-working in hospitals, territorial services or private practice-and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.
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Obesidade , Sobrepeso , Humanos , Obesidade/terapia , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/terapia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Adulto , Itália/epidemiologia , Comorbidade , Terapia Comportamental/métodos , Terapia Comportamental/normas , Guias de Prática Clínica como Assunto/normas , Gerenciamento Clínico , Cirurgia Bariátrica/métodosRESUMO
BACKGROUND: Thyroid dysfunction has been observed in patients with COVID-19, and endocrinologists are requested to understand this clinical issue. Pandemic-related restrictions and reorganization of healthcare services may affect thyroid disease management. OBJECTIVE AND METHODS: To analyze and discuss the relationship between COVID-19 and thyroid diseases from several perspectives. PubMed/MEDLINE, Google Scholar, Scopus, ClinicalTrial.gov were searched for this purpose by using free text words and medical subject headings as follows: "sars cov 2", "covid 19", "subacute thyroiditis", "atypical thyroiditis", "chronic thyroiditis", "hashimoto's thyroiditis", "graves' disease", "thyroid nodule", "differentiated thyroid cancer", "medullary thyroid cancer", "methimazole", "levothyroxine", "multikinase inhibitor", "remdesivir", "tocilizumab". Data were collected, analyzed, and discussed to answer the following clinical questions: "What evidence suggests that COVID-19 may induce detrimental consequences on thyroid function?"; "Could previous or concomitant thyroid diseases deteriorate the prognosis of COVID-19 once the infection has occurred?"; "Could medical management of thyroid diseases influence the clinical course of COVID-19?"; "Does medical management of COVID-19 interfere with thyroid function?"; "Are there defined strategies to better manage endocrine diseases despite restrictive measures and in-hospital and ambulatory activities reorganizations?". RESULTS: SARS-CoV-2 may induce thyroid dysfunction that is usually reversible, including subclinical and atypical thyroiditis. Patients with baseline thyroid diseases are not at higher risk of contracting or transmitting SARS-CoV-2, and baseline thyroid dysfunction does not foster a worse progression of COVID-19. However, it is unclear whether low levels of free triiodothyronine, observed in seriously ill patients with COVID-19, may worsen the disease's clinical progression and, consequently, if triiodothyronine supplementation could be a tool for reducing this burden. Glucocorticoids and heparin may affect thyroid hormone secretion and measurement, respectively, leading to possible misdiagnosis of thyroid dysfunction in severe cases of COVID-19. High-risk thyroid nodules require a fine-needle aspiration without relevant delay, whereas other non-urgent diagnostic procedures and therapeutic interventions should be postponed. DISCUSSION: Currently, we know that SARS-CoV-2 could lead to short-term and reversible thyroid dysfunction, but thyroid diseases seem not to affect the progression of COVID-19. Adequate management of patients with thyroid diseases remains essential during the pandemic, but it could be compromised because of healthcare service restrictions. Endocrine care centers should continuously recognize and classify priority cases for in-person visits and therapeutic procedures. Telemedicine may be a useful tool for managing patients not requiring in-person visits.
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COVID-19/epidemiologia , COVID-19/fisiopatologia , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/fisiopatologia , Glândula Tireoide/fisiopatologia , COVID-19/imunologia , Humanos , Doenças da Glândula Tireoide/imunologia , Testes de Função Tireóidea/tendências , Glândula Tireoide/imunologiaRESUMO
BACKGROUND AND AIMS: A significant increase in platelet count may be a risk factor for atherosclerotic cardiovascular disease. This study investigates the association between platelet number and glucose metabolism, evaluated by glycated hemoglobin (HbA1c) levels, in a apparently healthy population represented by overweight and obese subjects with normal glucose and HbA1c levels. METHODS AND RESULTS: As many as 240 subjects, 177 women and 63 men, aged 18-70 years, were enrolled. Body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressure levels, platelet count and fasting blood glucose, insulin, insulin resistance, HbA1c, uric acid, triglyceride, total cholesterol, high and low density lipoprotein cholesterol concentrations were evaluated. Concerning the univariate correlation analyses between platelets number and all other variables, platelet count was significantly (and positively) correlated only with HbA1c (P < 0.05) and female sex (P < 0.01). HbA1c (P < 0.05), female sex (P < 0.001), and diastolic blood pressure (P < 0.01), positively, and age (P < 0.05) and systolic blood pressure (P < 0.05), negatively, were significantly and independently associated to platelet count in a final multiple regression analysis. CONCLUSION: This is the first study showing a strong positive and independent relationship between HbA1c and platelet number in non-diabetic overweight and obese subjects.
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Plaquetas/metabolismo , Transtornos do Metabolismo de Glucose/sangue , Hemoglobinas Glicadas/metabolismo , Obesidade/sangue , Sobrepeso/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Feminino , Transtornos do Metabolismo de Glucose/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Sobrepeso/diagnóstico , Contagem de Plaquetas , Adulto JovemRESUMO
BACKGROUND AND AIM: A significant change of platelet number may be a risk factor for atherosclerotic cardiovascular disease. The aim of this study was to investigate the association between platelet number and early signs of atherosclerosis, evaluated by carotid intima-media thickness (c-IMT), in a apparently healthy population mainly represented by obese subjects. METHODS AND RESULTS: As many as 961 subjects, 686 women and 275 men, aged between 18 and 74 years, were enrolled in the study. Of these, 54 individuals (5.6% of all subjects) were normal weight, 259 individuals (27.0% of all subjects) were overweight, and 648 individuals (67.4% of all subjects) were obese. Waist circumference (WC) and blood glucose, insulin, total cholesterol, high and low density lipoprotein cholesterol, triglycerides and platelet count were also detected in all subjects, who underwent carotid echo color doppler ultrasound to measure c-IMT. c-IMT was significantly and positively associated to age (r = 0.204, P < 0.0001), fasting glucose (r = 0.073, P < 0.0240), total cholesterol (r = 0.096, P = 0.0031), and systolic and diastolic blood pressure (r = 0.140, P < 0.0001 and r = 0.119, P < 0.0003 respectively); c-IMT was significantly and negatively correlated with platelet count (r = -0.165, P < 0.0001). Only age (P < 0.0001) and systolic blood pressure (P = 0.0393), positively, and platelet number (P < 0.0001), negatively, were significantly and independently associated to c-IMT in a final multiple regression analysis. CONCLUSION: Lower platelet number represented an independent determinant of c-IMT in a population, mainly represented by obese patients. These results suggest that a decrease of platelet number may well be an early defensive mechanism in subjects developing the thickening of carotid artery.
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Plaquetas , Doenças das Artérias Carótidas/sangue , Artéria Carótida Primitiva/diagnóstico por imagem , Espessura Intima-Media Carotídea , Obesidade Metabolicamente Benigna/sangue , Ultrassonografia Doppler em Cores , Adolescente , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Pressão Sanguínea , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Metabolicamente Benigna/diagnóstico , Obesidade Metabolicamente Benigna/fisiopatologia , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: This study examined whether the AR-CAG repeat length might affect clinical characteristics (testis volume) seminal parameters (sperm count and its mobility) along with hormonal serum profile [FSH, LH, Testosterone (T) and Inhibin B (InhB)] both in idiopathic male infertility (IM) and in infertility due to a previous condition of cryptorchidism (CryM) or to Y chromosome long arm microdeletions (YM). DESIGN: Observational study without intervention(s). PATIENTS: One hundred and ten IM patients [90 idiopathic olizoospermic males (IOM) and 20 idiopathic azoospermic males (IAM)], 19 CryM male and 10 YM patients were included. Sixty-one age-matched healthy men who had fathered within 3 years were involved representing the control group (FM). RESULTS: AR-CAG repeats stretch was significantly longer in IOM (p<0.05), CryM (p<0.05) and YM (p<0.001) than FM. When the AR-CAG repeat tracts were subdivided in three subgroups according to the length of CAG repeats tract assessed in fertile subjects (the one with the middle (n 19-21) belonging to the 25 and 75 % inter-quartile, the ends belonging to the <25 % inter-quartile and >75 % inter-quartile, respectively), there was a statistically significant difference of distribution of AR-CAG tract length among fertile and different groups of infertile men (p=<0.0005; chi-square test). Moreover, the subgroup of AR-CAG repeat stretch with 22-28 triplets was associated with lower levels of InhB both in idiopathic oligozoospermic (Scheffe, Bonferroni and Dunett tests p=<0.01) and azoospermic men (Scheffe, Bonferroni and Dunett test p=<0.05), while, when FM and men with idiopathic infertility were gathered in a single group, both the subgroup of AR- CAG tract with 15-18 repeats and the one with 22-28 repeats are associated with lower testis volume, reduced sperm count and serum InhB levels. CONCLUSIONS: Our study showed that the outliers of AR-CAG repeat length seem to influence the function of AR, affecting testis volume and Sertoli cell function and consequently sperm production in both fertile and idiopathic infertile men.
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Infertilidade Masculina , Oligospermia , Receptores Androgênicos , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual , Repetições de Trinucleotídeos , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Deleção Cromossômica , Cromossomos Humanos Y/genética , Criptorquidismo , Infertilidade Masculina/genética , Oligospermia/genética , Oligospermia/patologia , Receptores Androgênicos/genética , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/patologia , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatogênese/genética , Repetições de Trinucleotídeos/genéticaRESUMO
BACKGROUND: Chronic stress is a condition of pressure on the brain and whole body, which in the long term may lead to a frank disease status, even including type 2 diabetes (T2D). Stress activates the hypothalamus-pituitary-adrenal axis with release of glucocorticoids (GCs) and catecholamines, as well as activation of the inflammatory pathway of the immune system, which alters glucose and lipid metabolism, ultimately leading to beta-cell destruction, insulin resistance and T2D onset. Alteration of the glucose and lipid metabolism accounts for insulin resistance and T2D outcome. Furthermore, stress-related subversion of the intestinal microbiota leads to an imbalance of the gut-brain-immune axis, as evidenced by the stress-related depression often associated with T2D. Inflammatory mechanisms: A condition of generalized inflammation and subversion of the intestinal microbiota represents another facet of stress-induced disease. In fact, chronic stress acts on the gut-brain axis with multi-organ consequences, as evidenced by the association between depression and T2D. Novel Therapeutic Options: Oxidative stress with the production of reactive oxygen species and cytokine-mediated inflammation represents the main hallmarks of chronic stress. ROS production and pro-inflammatory cytokines represent the main hallmarks of stress-related disorders, and therefore, the use of natural antioxidant and anti-inflammatory substances (nutraceuticals) may offer an alternative therapeutic approach to combat stress-related T2D. Single or combined administration of nutraceuticals would be very beneficial in targeting the neuro-endocrine-immune axis, thus, regulating major pathways involved in T2D onset. However, more clinical trials are needed to establish the effectiveness of nutraceutical treatment, dosage, time of administration and the most favorable combinations of compounds. Therefore, in view of their antioxidant and anti-inflammatory properties, the use of natural products or nutraceuticals for the treatment of stress-related diseases, even including T2D, will be discussed. Several evidences suggest that chronic stress represents one of the main factors responsible for the outcome of T2D.
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BACKGROUND: The aim of this study was to examine the relationship between thyroid hormones and smoking and several other parameters like age, gender, insulin, and anthropometric and metabolic parameters in subjects with a wide range of body mass index (BMI). PATIENTS AND METHODS: A total of 931 euthyroid normal weight (BMI<25.0 kg/m2), overweight and obese subjects (BMI ≥25.0 kg/m2), 663 women and 268 men, aged 18-68 yr, were investigated. Fasting TSH, free T3 (FT3), free T4 (FT4), insulin, glucose, and lipid serum levels were determined. Waist circumference was measured as an indirect parameter of central fat accumulation. RESULTS: Smokers were younger (p<0.001) and showed higher FT3 (p<0.01), and triglyceride (p<0.01) levels and lower glucose (p<0.01) and HDL (p<0.001) concentrations than non smoking subjects. FT3 levels were directly associated with BMI (p<0.001), waist circumference (p<0.001), insulin (p<0.001), and triglyceride (p<0.01) levels and negatively correlated with age (p<0.001) and HDL-cholesterol levels (p<0.001). When a multiple regression analysis was performed with FT3 levels as the dependent variable, and smoking, age, gender, and TSH, insulin, triglyceride, and HDL-cholesterol serum concentrations as independent variables, FT3 levels maintained an independent positive association with smoking (p<0.05), age (p<0.001), male sex (p<0.001), waist circumference (p<0.05), and insulin levels (p<0.001). CONCLUSIONS: Smoking increases FT3 levels independently of age, gender, obesity, body fat distribution and metabolic parameters.
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Fumar/sangue , Tri-Iodotironina/sangue , Adolescente , Adulto , Idoso , Composição Corporal , Distribuição da Gordura Corporal , Índice de Massa Corporal , HDL-Colesterol/sangue , HDL-Colesterol/líquido cefalorraquidiano , Feminino , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Sobrepeso/sangue , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
BACKGROUND: There is a very high prevalence of obese women in the infertile population and many studies have highlighted the link between obesity and infertility. The aim of this study was to evaluate the prevalence of oligomenorrhea in uncomplicated obesity, and to examine whether this menstrual alteration is associated with anthropometric, hormonal, and metabolic parameters. PATIENTS AND METHODS: This is a cross-sectional study of 266 overweight and obese body mass index (BMI) > or =25.0 kg x m(-2)] women, all having apparent normal fertility. Measurements included BMI, central fat accumulation (evaluated by waist circumference), blood pressure levels, and fasting insulin, glucose, and lipid (triglycerides, total and HDL-cholesterol) serum concentrations, and insulin resistance [estimated by (homeostasis model assessment) HOMAIR] during the early follicular phase (days 2-5 of the menstrual cycle). RESULTS: One hundred and seventy-one (64.3%) of 266 women had normal menstrual cycles, 57 (21.4%) had oligomenorrhea, and 38 (14.3%) had hypermenorrhea and/or polimenorrhea. Women with oligomenorrhea had higher waist circumference, BMI, HOMAIR, and insulin levels than women with normal menstrual cycles. When association among oligomenorrhea and other variables (waist circumference, BMI, insulin and HOMAIR) was evaluated by logistic regression, and odds ratio was calculated per unit of SD increase, only waist circumference maintained a significant relationship with oligomenorrhea. CONCLUSIONS: This study shows that more than 20% of women with simple obesity have oligomenorrhea, and suggests that central fat accumulation seems to have a possible direct role in this menstrual alteration, independently of hyperinsulinemia and/or insulin resistance.
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Gordura Abdominal/fisiopatologia , Resistência à Insulina/fisiologia , Obesidade/complicações , Obesidade/fisiopatologia , Oligomenorreia/complicações , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Circunferência da CinturaRESUMO
BACKGROUND AND AIM: Soluble P-selectin (sP-sel) represents a marker of platelet activation. This study was addressed to investigate the associations of sP-sel plasma levels with anthropometric parameters, insulin resistance, and related metabolic and prothrombotic factors. METHODS AND RESULTS: 50 non-diabetic women, 17 with normal weight and 33 overweight and obese, aged 18-55 years, were examined. Measurements included body mass index (BMI), central fat accumulation (evaluated by waist circumference), systolic and diastolic blood pressure levels, fasting plasma concentrations of sP-sel, glucose, lipids (triglycerides, total cholesterol and HDL-cholesterol), insulin, and prothrombotic factors (plasminogen activator inhibitor-1, von Willebrand factor, fibrinogen), and insulin resistance (estimated by the homeostasis model assessment: HOMA(IR)). Overweight and obese women had higher fasting plasma sP-sel concentrations compared to normal-weight controls (P<0.05). sP-sel concentrations were positively correlated with BMI, HOMA(IR), systolic and diastolic blood pressure, fasting insulin, triglyceride and PAI-1 plasma levels (P<0.05 for all the correlations). When a multiple regression analysis was performed, with P-sel as dependent variable and all the other parameters as independent variables, P-sel did not maintain a significant relationship with any of these variables. CONCLUSIONS: s-P-selectin plasma concentrations are higher in overweight and obese insulin resistant subjects, thus possibly contributing to the cardiovascular risk of these patients. However, body fatness and insulin resistance are not independent determinants of fasting plasma sP-sel concentrations.
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Glicemia/metabolismo , Resistência à Insulina , Lipídeos/sangue , Obesidade/sangue , Selectina-P/sangue , Adolescente , Adulto , Antropometria , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Feminino , Fibrinogênio/análise , Humanos , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Ativação Plaquetária , Análise de Regressão , Fatores de Risco , Solubilidade , Fator de von Willebrand/análiseRESUMO
INTRODUCTION: Adipocytokines have been proposed as new mediators of the protective effects of fat mass on the skeleton. The aim of this study was to test the relationship between adiponectin, leptin, and bone mineral density (BMD), independently of body composition, insulin resistance, and other factors known to affect bone metabolism. METHODS: Thirty-six post-menopausal non-diabetic elderly women, with ages ranging from 66 to 77 yr took part in the study. In all subjects we evaluated body weight, height, body mass index (BMI), waist circumference, adiponectin, leptin, insulin, DHEAS, and homeostasis model assessment of insulin resistance (HOMA), as well as yr since menopause. Total body fat mass (FM) and BMD at whole body and femoral level were measured with Dual energy X-ray Absorptiometry (DXA). Volumetric BMD was defined as the ratio between total body BMD and height. RESULTS: Leptin was positively and adiponectin negatively related with whole body and femoral BMD. Positive associations between insulin, HOMA, DHEAS, and BMD measures were also found. After adjusting for FM, only adiponectin maintained a significant relation with whole body and femoral BMD; the strength of this association was reduced after adjustment for insulin resistance, estimated by HOMA. In stepwise multiple linear regression analyses adiponectin explained 11.7% of total BMD variance, 17.4% of femoral neck BMD variance, and 30.7% of volumetric BMD variance, independently of BMI, FM, leptin, HOMA, and DHEAS. CONCLUSIONS: The present study may suggest possible involvement of adiponectin in bone metabolism, independently of FM and insulin resistance even in elderly post-menopausal women.
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Adiponectina/sangue , Densidade Óssea/fisiologia , Sulfato de Desidroepiandrosterona/sangue , Resistência à Insulina/fisiologia , Leptina/sangue , Pós-Menopausa/sangue , Idoso , Composição Corporal/fisiologia , Feminino , Humanos , Gordura Subcutânea/metabolismoRESUMO
BACKGROUND: Obesity is associated with a chronic low-grade inflammatory condition. Haptoglobin is a glycoprotein involved in the acute-phase response to inflammation, and it is increased in obese subjects. The possibility that hyperinsulinemia and/or insulin resistance may directly increase haptoglobin levels has never been tested. The aim of this study was to investigate the associations of haptoglobin serum levels with anthropometric parameters, insulin levels, insulin resistance and related metabolic variables in overweight and obese women. PATIENTS AND METHODS: This is a cross-sectional study of 194 non-diabetic overweight and obese subjects, aged 18-68 yr. Measurements included body mass index (BMI), central fat accumulation [evaluated by waist circumference (WC)], systolic and diastolic blood pressure, and fasting concentrations of haptoglobin, insulin, glucose, lipids (triglycerides, total cholesterol, and HDL-cholesterol), and insulin resistance as estimated by the homeostasis model assessment (HOMAIR). RESULTS: Haptoglobin serum levels showed a positive association with BMI (p<0.001), WC (p<0.001), HOMAIR (p<0.001), and fasting insulin (p<0.001), triglyceride (p<0.001) and glucose (p<0.05) blood levels. However, only insulin maintained a significant independent association with haptoglobin (p<0.001) when a multiple regression analysis was performed and age, BMI (or WC), blood pressure levels, HOMAIR, and fasting insulin, glucose, and lipid blood concentrations were entered as independent variables. CONCLUSIONS: Higher haptoglobin serum levels seem to be a strong marker of hyperinsulinemia, independently of BMI, body fat distribution, insulin resistance and related parameters.
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Biomarcadores/sangue , Haptoglobinas/metabolismo , Hiperinsulinismo/sangue , Obesidade/sangue , Adolescente , Adulto , Idoso , Pressão Sanguínea , Índice de Massa Corporal , Peso Corporal , Estudos Transversais , Feminino , Humanos , Hiperinsulinismo/complicações , Pessoa de Meia-Idade , Obesidade/complicaçõesRESUMO
OBJECTIVE: A cross-sectional analysis of dietary fiber intake was performed in European type 1 diabetic patients enrolled in the EURODIAB IDDM Complications Study to explore its potential relationship to serum cholesterol levels and the prevalence of cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Dietary intake was assessed by a standardized 3-day dietary record. For analysis of fiber intake (total, soluble, and insoluble) and its associations with CVD (past history or electrocardiogram abnormalities), complete data were available from 1,050 male and 1,012 female individuals. Relationships of fiber intakes to serum cholesterol levels (total, HDL, and LDL cholesterol) were examined in 926 men and 881 women with type 1 diabetes. RESULTS: Higher intakes of total fiber (g/day) were independently associated with significantly higher levels of HDL cholesterol in male (P = 0.01) and female individuals (P = 0.03). Fiber intakes of men with type 1 diabetes were also inversely related to ratios of total cholesterol to HDL cholesterol (P = 0.0001) and levels of LDL cholesterol (P = 0.0002). A protective effect of total fiber intake against CVD was observed for female subjects, where a significant trend was maintained after adjustment for potential confounders, including energy and saturated fat (P = 0.03 vs. P = 0.2 in men). Results were similar in separate analyses of soluble and insoluble fiber. CONCLUSIONS: The present study demonstrates that higher fiber intakes are independently related to beneficial alterations of the serum cholesterol pattern in men and to a lower risk for CVD in European insulin-dependent women. Beneficial effects can already be observed for fiber amounts within the range commonly consumed by outpatients with type 1 diabetes.
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Doenças Cardiovasculares/complicações , Colesterol/sangue , Diabetes Mellitus Tipo 1/complicações , Fibras na Dieta/administração & dosagem , Adulto , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Registros de Dieta , Ingestão de Energia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , PrevalênciaRESUMO
OBJECTIVE: To determine whether the severity of retinopathy is higher in a group of NIDDM patients with sBP greater than or equal to 140 mmHg compared with NIDDM patients with sBP less than 140 mmHg. RESEARCH DESIGN AND METHODS: Ophthalmoscopy and FAG were conducted among a group of NIDDM patients with either a sBP above (n = 54) or below (n = 55) 140 mmHg. The groups were matched according to diabetes duration, metabolic control (HbA1c), and AER. RESULTS: Patients with sBP greater than 140 mmHg had a higher prevalence of retinopathy, as established according to a rating scale (4.9 +/- 3.8 vs. 3.2 +/- 3.3, P less than 0.02); furthermore, their BMI values were higher (28.1 +/- 4.5 vs. 24.9 +/- 4.1 kg/m2, P less than 0.001). The group of normotensive subjects showed the highest rate of low grading (0-2) values. However, the highest prevalence rates of 8-10 grading values (proliferative retinopathy) were found in the hypertensive group. CONCLUSIONS: These data suggest that sBP values greater than or equal to 140 mmHg favor the onset of retinopathy in NIDDM patients during their 1st 10 yr of disease.
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Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/fisiopatologia , Hipertensão/complicações , Pressão Sanguínea , Índice de Massa Corporal , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/patologia , Diástole , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Retina/patologia , Retina/fisiopatologia , Fatores de Risco , Sístole , Fatores de TempoRESUMO
The aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a 'real-life setting'. Forty-three obese, diabetic and hypogonadal men (aged 45-59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000-3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 µg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = <7.5% (<58 nmol/mol)] and a significant reduction in body weight (p < 0.01), but also a further increase in SHBG (p < 0.05) and T (p < 0.01) plasma levels as well as a significant increment of IIEF score (T3). Conversely, at T3 G1Y and G2Y, who received the combined therapy with TRT and Met for the second year, showed a partial failure of that treatment given that there was no improvement of the IIEF score and they showed a significant rise in serum HbA1c (p < 0.05) and weight (p < 0.04) compared with the assessments at T2. These results suggest that TRT could improve clinical and metabolic parameters in obese, type 2 diabetic men with ED and overt hypogonadism (independently of when T deficit occurred). Furthermore, in case of insufficient metabolic control the addition of L to TRT and Met regimen allows to achieve serum T levels in the range of healthy men, as well as to reach glycaemic target and to lower weight, leading to a considerable improvement of ED.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Disfunção Erétil/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Hipoglicemiantes/uso terapêutico , Hipogonadismo/tratamento farmacológico , Incretinas/uso terapêutico , Liraglutida/uso terapêutico , Metformina/uso terapêutico , Obesidade/tratamento farmacológico , Ereção Peniana/efeitos dos fármacos , Testosterona/análogos & derivados , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Quimioterapia Combinada , Disfunção Erétil/sangue , Disfunção Erétil/diagnóstico , Disfunção Erétil/fisiopatologia , Hemoglobinas Glicadas/metabolismo , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Hipogonadismo/sangue , Hipogonadismo/diagnóstico , Incretinas/efeitos adversos , Liraglutida/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Estudos Retrospectivos , Comportamento de Redução do Risco , Testosterona/efeitos adversos , Testosterona/sangue , Testosterona/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Redução de Peso/efeitos dos fármacosRESUMO
AIM: The aim of this paper was to evaluate the hypothesis that pretreatment with dehydroepiandrosterone (DEHA) may improve the result on in vitro fertilization (IVF) and the pregnancy outcome among infertile women with normal ovarian reserve. METHODS: Double-blind, randomized, placebo-controlled study; 52 infertile patients received the long protocol IVF. Patients in Group 1, received 75 mg of DHEA once a day, 8 weeks before starting the IVF cycle and during treatment; control group (Group 2) received placebo. The primary endpoint was pregnancy, live birth and miscarriage rates, secondary endpoint was standard IVF parameters such us stimulation duration (hCG day), E2 on HCG-day, endometrial thickness, number of retrieved oocytes, metaphase II oocytes, embryos transferred and score of leading embryos transferred. RESULTS: Patients in the DHEA group had a significantly higher live birth rate compared with controls (P<0.05). Miscarriage rate was higher in control group (P<0.05). CONCLUSION: DHEA supplementation could have a beneficial effect on IVF outcome in infertile women with normal ovarian reserve.
Assuntos
Desidroepiandrosterona/administração & dosagem , Fertilização in vitro/métodos , Infertilidade Feminina , Resultado da Gravidez , Aborto Espontâneo/epidemiologia , Adulto , Gonadotropina Coriônica/sangue , Método Duplo-Cego , Feminino , Humanos , Oócitos/metabolismo , Reserva Ovariana/fisiologia , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Resultado do TratamentoRESUMO
Adipose precursor cells from male rats were exposed in primary culture to testosterone (T) or dihydrotestosterone (DHT), and their effects on the regulation of lipolysis were studied. T, but not DHT, stimulated catecholamine-induced lipolysis in a dose-dependent manner, including physiological concentrations. The effect was equally pronounced with isoproterenol (a pure beta-adrenergic agonist) and norepinephrine (a mixed alpha 2- and beta-adrenergic agonist). The higher lipolytic capacity of catecholamines on T-treated cells was paralleled by a similar increase in the number of beta-adrenoceptors in the cells, without a change in the receptor affinity, suggesting that T induced new synthesis or externalization of beta-adrenoceptors. Both T and DHT stimulated forskolin-induced lipolysis, suggesting an androgen effect at the level of the catalytic subunit of adenylate cyclase. The pertussis toxin-stimulated lipolysis was not influenced by the presence of androgens in the culture medium, and no effect was seen on the antilipolytic effect of insulin. These effects did not disappear in the presence of an aromatase inhibitor, suggesting that the T effects were not mediated by conversion to estrogens. These cells showed specific saturable binding for androgens, with a Kd in the range of androgen concentrations shown to be active. In conclusion, androgens enhance the lipolytic capacity of these cells by increasing the apparent number of beta-adrenoceptors (T only) and the activity of adenylate cyclase (both T and DHT). These changes are not mediated by conversion to estrogens. These effects probably occur via binding to specific androgen receptors.
Assuntos
Tecido Adiposo/metabolismo , Di-Hidrotestosterona/farmacologia , Lipólise/efeitos dos fármacos , Células-Tronco/metabolismo , Testosterona/farmacologia , Animais , Membrana Celular/metabolismo , Células Cultivadas , Colforsina/farmacologia , Glicerol/metabolismo , Insulina/farmacologia , Isoproterenol/farmacologia , Masculino , Metribolona/metabolismo , Norepinefrina/farmacologia , Ratos , Ratos Endogâmicos , Receptores Adrenérgicos beta/metabolismoRESUMO
The influence of androgen status on the regulation of lipolysis and number of beta-adrenoceptors in isolated adipocytes was studied in male rats. Castration resulted in decreased catecholamine-induced as well as forskolin-induced lipolysis. beta-adrenoceptor number, examined by a whole cell cyanopindolol binding assay, was also diminished to a similar extent. Testosterone treatment of castrated rats normalized lipolysis as well as beta-adrenoceptor number. These results demonstrate that testosterone stimulates catecholamine-induced lipolysis in vivo by increasing the number of beta-adrenoceptors as well as the activity of adenylate cyclase, confirming previous in vitro studies performed in adipose precursor cells.
Assuntos
Tecido Adiposo/metabolismo , Isoproterenol/farmacologia , Lipólise/efeitos dos fármacos , Receptores Adrenérgicos beta/metabolismo , Testosterona/farmacologia , Tecido Adiposo/efeitos dos fármacos , Animais , Células Cultivadas , Iodocianopindolol , Cinética , Masculino , Orquiectomia , Pindolol/análogos & derivados , Pindolol/metabolismo , Ratos , Ratos Endogâmicos , Receptores Adrenérgicos beta/efeitos dos fármacos , Valores de Referência , Regulação para CimaRESUMO
In the previous studies we have shown that testosterone increases lipolytic responsiveness to catecholamines in rat white adipocytes, and that is associated with an up-regulation of beta-adrenergic receptor density. However, the postreceptor events involved in the testosterone induced enhancement of beta-adrenergic receptor activated lipolysis in these cells have not been adequately studied, and were therefore investigated in the present study. Male Sprague Dawley rats were divided into three groups: control, castrated, and castrated treated with testosterone. The beta-adrenergic receptor-mediated cAMP accumulation, measured with RIA after isoproterenol (a beta-adrenergic agonist) stimulation was decreased in castrated rats, and reversed by testosterone treatment, suggesting a testosterone effect at or proximal to adenylate cyclase. However, no differences between the groups were found in abundance of G alpha protein messenger RNAs (G alpha s, G alpha i-1, and G alpha i-2) as analyzed by Northern blot and a solution hybridization RNase protection assay, or in G protein mass measured with a quantitative enzyme-linked immunosorbent assay in fat cell membrane preparation. Lipolysis stimulated by N6-monobutyryl-cAMP was reduced in castrated rats and recovered by testosterone treatment, suggesting that components distal to the adenylate cyclase, i.e. protein kinase A (PKA) and/or hormone sensitive lipase (HSL) also are involved in testosterone regulation of lipolysis. In conclusion, these and previous results suggest that the testosterone-induced increase in lipolytic response to catecholamines in rat white adipocytes is mediated through several events including an increased beta-adrenergic receptor density, probably an increased adenylate cyclase activity and an increased protein kinase A/hormone sensitive lipase activity at the postreceptor level with apparent absence of effect on the expression of G-proteins.
Assuntos
Tecido Adiposo/metabolismo , Receptores Adrenérgicos beta/fisiologia , Testosterona/farmacologia , Regulação para Cima/fisiologia , Adenilil Ciclases/metabolismo , Tecido Adiposo/citologia , Animais , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Masculino , Orquiectomia , Proteínas Quinases/metabolismo , RNA Mensageiro/metabolismo , Ratos , Esterol Esterase/metabolismoRESUMO
As PAI-1, a cardiovascular risk factor linked to insulin-resistance, may be influenced by a 4G/5G gene polymorphism in disease states, we studied both PAI-1 plasma concentration (PAI-1:Ag) and 4G/5G polymorphism, and their relationship with anthropometric and endocrinemetabolic parameters in 93 obese patients and 79 lean normal subjects. In obese patients PAI-1:Ag levels were significantly increased, namely in males and in those with central obesity, and tightly related to the insulin-resistance parameters. In obese patients the 4G/5G polymorphism was a determinant of PAI-1:Ag levels, which were highest in 4G/4G, intermediate in 4G/5G and lowest in 5G/5G genotype carriers. PAI-1:Ag levels were significantly associated with most of anthropometric and endocrine-metabolic parameters only in 4G allele obese carriers. Moreover, only in patients with central obesity was the relationship between genotype and PAI-1 concentration maintained, with the highest levels in the 4G/4G patients. In each genotype subset of patients with central, but not peripheral, obesity PAI-1:Ag levels were significantly increased compared to their lean counterparts. In conclusion, the 4G/5G polymorphism may influence PAI-1 expression in obesity, with a crucial role in central but not peripheral adiposity. Since subjects with central obesity are at high risk for cardiovascular disease, the effects of the 4G/5G polymorphism on PAI-1 concentration may further enhance this risk.
Assuntos
Obesidade/sangue , Obesidade/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Polimorfismo Genético , Adulto , Biomarcadores/sangue , Pressão Sanguínea , Constituição Corporal , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Pós-Menopausa , Regiões Promotoras Genéticas , Fatores SexuaisRESUMO
Adipose tissue has been recognized as a major peripheral metabolic target of estrogens. The present study was addressed to examine in female rats whether differences in the adipose tissue mRNA expression of alpha-subunit of stimulatory (Gs) and/or inhibitory (Gi) G-proteins exist between intact and ovariectomized rats, the latter with or without estradiol or testosterone treatment. The fat cell membrane protein amount of Gs and Gi alpha-subunit also was examined. All these parameters were evaluated in parametrial fat tissue samples obtained from 40 female Sprague-Dawley rats. A group of rats (N = 20) was investigated for evaluation of mRNA expression and another group (N = 20) for quantification of the protein amount of Gs and Gi alpha-subunit. Each group was represented by five control rats (sham-operated), five ovariectomized (OVX) rats, five ovariectomized rats treated with estradiol (OVXE) and five ovariectomized rats treated with testosterone (OVXT). Ribonucleic acid extracted from adipose tissue and analyzed by northern blot with G alpha s, G alpha i-3 cRNA probes revealed three major bands with estimated sizes of 1.9, 3.5 and 2.35 kb, respectively. Messenger RNA quantitative analysis, by a solution of hybridization RNAase protection assay on total nucleic acid samples, showed that the amount of G alpha i-1 and G alpha i-2 mRNA was similar within the different groups, whereas the G alpha s mRNA was significantly less abundant (p < 0.01) in OVX and OVXT rats than in control or OVXE rats. No difference in G alpha s mRNA content was found between control and OVXE rats.(ABSTRACT TRUNCATED AT 250 WORDS)