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1.
Obes Facts ; 14(5): 543-549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34482305

RESUMO

INTRODUCTION: Overweight and obesity are associated with a more severe COronaVirus Disease 19 (COVID-19). Adipose tissue-related chronic inflammation could be a promoter for the occurrence of the cytokine storm that predicts aggravation of COVID-19. The primary aim was to investigate if this increased risk for more severe COVID-19 was associated with a higher inflammatory response. METHODS: We enrolled patients <75 years old hospitalized in a medical COVID-19 ward with SARS-CoV-2-related pneumonia. Patients were classified according to BMI as normal weight, overweight, and obesity. Laboratory parameters were measured at admission and every second day during the hospital stay. RESULTS: Ninety patients (64.4% males; median age 61 years) were enrolled. Invasive mechanical ventilation (IMV) was needed in 9% of the patients with normal weight, in 32.4% of the patients with overweight, and in 12.9% of the patients with obesity (p = 0.045). Maximal C-reactive protein (CRP) level during hospital stay was 92 (48-122) mg/L in patients with normal weight, 140 (82-265) mg/L in patients with overweight, and 117 (67-160) mg/L in patients with obesity (p = 0.037). Maximal ferritin values were 564 (403-1,379) µg/L in patients with a normal weight, 1,253 (754-2,532) µg/L in patients with overweight, and 828 (279-1,582) µg/L in patients with obesity (p = 0.015). CONCLUSION: Patients with overweight and obesity required more IMV and had higher peaks of CRP and ferritin than patients with normal weight during COVID-19.

2.
Nutrients ; 13(8)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34444930

RESUMO

Fewer studies compared the improvement of plasma lipid levels after different types of surgery, in particular compared to one-anastomosis gastric bypass (OAGB). The aim of our study was to investigate how laparoscopic sleeve gastrectomy (LSG) and OAGB impact on weight loss and lipid profile 18 months after surgery, in patients with severe obesity. Forty-six patients treated with OAGB were matched to eighty-eight patients submitted to LSG. Weight loss after OAGB (33.2%) was more evident than after LSG (29.6%) (p = 0.024). The difference in the prevalence of dyslipidemia showed a statistically significant reduction only after OAGB (61% versus 22%, p < 0.001). After adjustment for delta body mass index (BMI), age and sex, we demonstrated a statistically significant decrease of the differences between the changes before and after (delta Δ) the two surgery procedures: Δ total cholesterol values (p < 0.001), Δ low density lipoprotein-cholesterol values (p < 0.001) and Δ triglycerides values (p = 0.007). Patients with severe obesity undergoing to OAGB presented a better improvement of lipid plasma values than LSG patients. The reduction of lipid plasma levels was independent of the significant decrease of BMI after surgery, of age and of sex.


Assuntos
Gastrectomia/métodos , Derivação Gástrica/métodos , Lipídeos/sangue , Obesidade Mórbida/sangue , Adolescente , Adulto , Idoso , Antropometria , Índice de Massa Corporal , Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Período Pós-Operatório , Resultado do Tratamento , Triglicerídeos/sangue , Perda de Peso , Adulto Jovem
3.
Pathol Res Pract ; 221: 153451, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33932720

RESUMO

Few studies have focused on COVID-19 patients' hepatic histopathological features. Many of the described morphological landscapes are non-specific and possibly due to other comorbidities or to Sars-CoV-2-related therapies. We describe the hepatic histopathological findings of 3 liver biopsies obtained from living COVID-19 patients in which active SARS-CoV-2 infection was molecularly confirmed and biopsied because of significant alterations of liver function tests and 25 livers analyzed during COVID-19-related autopsies. Main histopathological findings were (i) the absence of significant biliary tree or vascular damages, (ii) mild/absent lymphocytic hepatitis; (iii) activation of (pigmented) Kupffer cells, (iv) hepatocellular regenerative changes, (v) the presence of steatosis, (vi) sinusoidal ectasia, micro-thrombosis and acinar atrophy in autopsy specimens No viral particle actively infecting the hepatic or endothelial cells was detected at in situ hybridization. The morphological features observed within the hepatic parenchyma are not specific and should be considered as the result of an indirect insult resulting from the viral infection or the adopted therapeutic protocols.


Assuntos
COVID-19/complicações , Hepatopatias/patologia , Hepatopatias/virologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
4.
Eat Weight Disord ; 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33811619

RESUMO

PURPOSE: Obstructive Sleep Apnea (OSA) is associated with the presence and severity of Non-Alcoholic Fatty Liver Disease (NAFLD). We aimed to investigate the relationship between the severity of OSA and NAFLD and to recognize a polysomnographic parameter correlated with progression of fibrosis, determined by a non-invasive score of liver fibrosis, FIBrosis-4 index (FIB-4), in patients affected by severe obesity and OSA. METHODS: We enrolled 334 patients (Body Mass Index, BMI 44.78 ± 8.99 kg/m2), divided into classes according to severity of OSA evaluated with Apnea Hypopnea Index (AHI): OSAS 0 or absent (17%), mild OSA (26%), moderate OSA (20%), severe OSAS (37%). We studied anthropometric, polysomnographic, biochemical data and FIB-4. A multiple regression model was computed to identify a polysomnographic independent predictor of FIB-4 among those parameters previously simple correlated with FIB-4. RESULTS: The severity of OSA was associated with a decrease in High-Density Lipoprotein-cholesterol (HDL) and an increase in BMI, triglycerides, Homeostasis model assessment insulin-resistance index (HOMA), transaminases and FIB-4. FIB-4 correlated with sex, age, BMI, AHI, mean percentage oxyhaemoglobin (meanSaO2%), number of desaturations, platelets, transaminases, HDL, triglycerides and HOMA. The only variables independently related to FIB-4 were sex, BMI, triglycerides and meanSpO2 (r = 0.47, AdjRsqr = 0.197). CONCLUSION: MeanSpO2% represented an independent determinant for the worsening of FIB-4 in patients with severe obesity and OSA. Hence, it could hypothesize a clinical role of meanSaO2% in recognizing patients with obesity and OSA and higher risk of developing advanced fibrosis and, thus, to undergo further investigation. LEVEL III: Evidence obtained from well-designed cohort analytic studies.

5.
Rev Endocr Metab Disord ; 21(3): 297-306, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32734395

RESUMO

Bariatric surgery (BS) is today the most effective therapy for inducing long-term weight loss and for reducing comorbidity burden and mortality in patients with severe obesity. On the other hand, BS may be associated to new clinical problems, complications and side effects, in particular in the nutritional domain. Therefore, the nutritional management of the bariatric patients requires specific nutritional skills. In this paper, a brief overview of the nutritional management of the bariatric patients will be provided from pre-operative to post-operative phase. Patients with severe obesity often display micronutrient deficiencies when compared to normal weight controls. Therefore, nutritional status should be checked in every patient and correction of deficiencies attempted before surgery. At present, evidences from randomized and retrospective studies do not support the hypothesis that pre-operative weight loss could improve weight loss after BS surgery, and the insurance-mandated policy of a preoperative weight loss as a pre-requisite for admission to surgery is not supported by medical evidence. On the contrary, some studies suggest that a modest weight loss of 5-10% in the immediate preoperative period could facilitate surgery and reduce the risk of complications. Very low calories diet (VLCD) and very low calories ketogenic diets (VLCKD) are the most frequently used methods for the induction of a pre-operative weight loss today. After surgery, nutritional counselling is recommended in order to facilitate the adaptation of the eating habits to the new gastro-intestinal physiology. Nutritional deficits may arise according to the type of bariatric procedure and they should be prevented, diagnosed and eventually treated. Finally, specific nutritional problems, like dumping syndrome and reactive hypoglycaemia, can occur and should be managed largely by nutritional manipulation. In conclusion, the nutritional management of the bariatric patients requires specific nutritional skills and the intervention of experienced nutritionists and dieticians.

6.
Rev Endocr Metab Disord ; 21(4): 449, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32803692

RESUMO

The original version of this article unfortunately, has the incorrect title reported in the published paper.

7.
Obesity (Silver Spring) ; 28(9): 1600-1605, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32463545

RESUMO

OBJECTIVE: The clinical manifestations of coronavirus disease (COVID-19) run from asymptomatic disease to severe acute respiratory syndrome. Older age and comorbidities are associated to more severe disease. A role of obesity is suspected. METHODS: Patients hospitalized in the medical COVID-19 ward with severe acute respiratory syndrome coronavirus 2-related pneumonia were enrolled. The primary outcome of the study was to assess the relationship between the severity of COVID-19 and obesity classes according to BMI. RESULTS: A total of 92 patients (61.9% males; age 70.5 [13.3] years) were enrolled. Patients with overweight and obesity were younger than patients with normal weight (68.0 [12.6] and 67.0 [12.6] years vs. 76.1 [13.0] years, P < 0.01). A higher need for assisted ventilation beyond pure oxygen support (invasive mechanical ventilation or noninvasive ventilation) and a higher admission to intensive or semi-intensive care units were observed in patients with overweight and obesity (P < 0.01 and P < 0.05, respectively) even after adjusting for sex, age, and comorbidities (P < 0.05 and P < 0.001, respectively) or when patients with dementia or advanced cancer were removed from the analysis (P < 0.05). CONCLUSIONS: Patients with overweight and obesity admitted in a medical ward for severe acute respiratory syndrome coronavirus 2-related pneumonia, despite their younger age, required more frequently assisted ventilation and access to intensive or semi-intensive care units than normal weight patients.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Obesidade/complicações , Pneumonia Viral/complicações , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , COVID-19 , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Hospitalização , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Respiração Artificial , SARS-CoV-2
8.
Aging Male ; 23(5): 464-468, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30449231

RESUMO

Male obesity is known to be associated with hypogonadism, which can be reverted after surgical weight reduction. However, the evidence about how rapidly this effect rises after surgery and what consequences each procedure have on prostate function and prostatic-specific antigen (PSA) concentration is scarce. So, we evaluated total testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone and PSA plasma levels in a group of 29 Caucasian obese men (BMI - 43.4 ± 8.5 kg/m2) before and one month after sleeve gastrectomy. 19 lean healthy male subjects were considered as controls. As expected, obese patients showed a high prevalence of hypogonadism (51.6%) at baseline, with reduced total testosterone compared to lean controls (10.8 ± 3.5 vs 15.7 ± 4.2 nmol/l, p < .01), higher estradiol (124.4 ± 46.5 vs 78.7 ± 39.6 pmol/l, p < .01), lower luteinizing hormone and follicle stimulating hormone (3.6 ± 1.3 and 2.5 ± 0.9 vs 5.2 ± 2.4 and 5.9 ± 3.8 U/L, respectively, p < .05) plasma levels. One month after surgery, patients showed a significant body weight reduction (-17.2 ± 6.7 kg) with increased total testosterone (from 10.8 ± 3.5 to 18.9 ± 4.9 nmol/l, p < .001), reduced estradiol (from 124.4 ± 46.5 to 96.1 ± 34.3 pmol/l, p < .05) and increased PSA (from 0.74 ± 0.38 to 1.0 ± 0.51 µg/l, p < .001). These results confirm that hypogonadism is highly prevalent in obese males, but they also show that it can be early reversed after sleeve gastrectomy, further confirming the strong indication to surgery of hypogonadal patients with severely reduced quality of life. Higher testosterone levels may be responsible for the increase of PSA observed after surgery; however, PSA concentration has to be monitored over time to avoid underrating of potential severe prostate diseases.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31440209

RESUMO

Determinants of resting energy expenditure (REE) in humans are still under investigation, especially the association with insulin resistance. Brown adipose tissue (AT) regulates energy expenditure through the activity of the uncoupling protein 1 (UCP1). White AT browning is the process by which some adipocytes within AT depots acquire properties of brown adipocytes ("brite" adipocytes) and it correlates with metabolic improvement. We analyzed determinants of REE in patients with obesity and assessed UCP1 expression as a "brite" marker in abdominal subcutaneous AT (SAT) and visceral omental AT (VAT). Clinical data, REE, free fat mass (FFM), and fat mass (FM) were determined in 209 patients with obesity. UCP1, PPARG coactivator 1 alpha (PPARGC1A), transcription factor A, mitochondrial (TFAM), T-box transcription factor 1 (TBX1), and solute carrier family 27 member 1 (SLC27A1) expression was assayed in SAT and VAT samples, obtained during sleeve gastrectomy from 62 patients with obesity. REE and body composition data were also available for a subgroup of 35 of whom. In 209 patients with obesity a multiple regression model was computed with REE as the dependent variable and sex, waist, FFM, FM, homeostasis model assessment-insulin resistance (HOMA), interleukin-6 and High Density Lipoprotein-cholesterol as the independent variables. Only FFM, FM and HOMA were independently correlated with REE (r = 0.787, AdjRsqr = 0.602). In each patient VAT displayed a higher UCP1, PPARGC1A, TFAM, TBX1, and SLC27A1 expression than SAT and UCP1 expression in VAT (UCP1-VAT) correlated with Body Mass Index (BMI) (r = 0.287, p < 0.05). Introducing UCP1-VAT in the multivariate model, we showed that FFM, HOMA, interleukin-6, High Density Lipoprotein-cholesterol, and UCP1-VAT were independent factors correlated with REE (r = 0.736, AdjRsqr = 0.612). We confirmed that REE correlates with FFM, FM and HOMA in a large cohort of patients. Our results clearly showed that UCP1-VAT expression was significantly increased in severe human obesity (BMI > 50 kg/m2) and that it behaved as an independent predictor of REE. Lastly, we suggest that an increased REE and browning in metabolically complicated severe obesity could represent an effort to counteract further weight gain.

10.
Sci Rep ; 9(1): 11333, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31383894

RESUMO

Although obesity represents a risk factor for the development of type 2 diabetes mellitus (T2DM), the link between these pathological conditions is not so clear. The manner in which the different elements of adipose tissue (AT) interplay in order to grow has been suggested to have a role in the genesis of metabolic complications, but this has not yet been fully addressed in humans. Through IHC, transmission electron microscopy, cytometry, and in vitro cultures, we described the morphological and functional changes of subcutaneous and visceral AT (SAT and VAT) in normoglycemic, prediabetic and T2DM patients with obesity compared to lean subjects. In both SAT and VAT we measured a hypertrophic and hyperplastic expansion, causing similar vascular rarefaction in obese patients with different degrees of metabolic complications. Capillaries display dysfunctional basement membrane thickening only in T2DM patients evidencing VAT as a new target of T2DM microangiopathy. The largest increase in adipocyte size and decrease in adipose stem cell number and adipogenic potential occur both in T2DM and in prediabetes. We showed that SAT and VAT remodeling with stemness deficit is associated with early glucose metabolism impairment suggesting the benefit of an AT-target therapy controlling hypertrophy and hyperplasia already in prediabetic obese patients.


Assuntos
Gordura Abdominal/patologia , Diabetes Mellitus Tipo 2/patologia , Glucose/metabolismo , Obesidade/patologia , Gordura Subcutânea/patologia , Gordura Abdominal/metabolismo , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Gordura Subcutânea/metabolismo
11.
Obes Facts ; 12(3): 291-306, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31104052

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obesity and its presence should be screened. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity, but its effects on NAFLD are still to be firmly established. The diagnosis of non-alcoholic steatohepatitis (NASH) is currently performed by liver biopsy, a costly and invasive procedure. Squamous cell carcinoma antigen-IgM (SCCA-IgM) is a biomarker of viral hepatitis to hepatocellular carcinoma development and its role in NAFLD to NASH progression has not yet been investigated. OBJECTIVE: The aim of this study was to evaluate SCCA-IgM as a non-invasive biomarker of NAFLD/NASH in patients with different degrees of metabolic-complicated obesity before and after LSG. METHOD: Fifty-six patients with obesity were studied before and 12 months after LSG; anthropometric, biochemical, clinical, and imaging data were collected. RESULTS: At baseline steatosis was strongly associated with the glycaemic profile (p = 0.016) and was already present in prediabetic patients with obesity (82%). Only 3 patients had an SCCA-IgM level above the normal cut-off. SCCA-IgM titre did not change according to glycaemic profile or steatosis. Metabolic and inflammatory factors and transaminases significantly reduced after LSG-induced weight loss, except for SCCA-IgM. The ALT/AST ratio decreased post-LSG correlated with BMI (r = 0.297, p = 0.031), insulin (r = 0.354, p = 0.014), and triglycerides (r = 0.355, p = 0.009) reduction. CONCLUSIONS: Our results confirm the tight link between NAFLD and metabolic complications, suggesting prediabetes as a new risk factor of steatosis. SCCA-IgM does not seem to have a role in the identification and prognosis of NAFLD.


Assuntos
Antígenos de Neoplasias/imunologia , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Imunoglobulina M/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade/sangue , Estado Pré-Diabético/sangue , Serpinas/imunologia , Adulto , Antígenos de Neoplasias/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Seguimentos , Gastrectomia/métodos , Gastrectomia/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/cirurgia , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/cirurgia , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/cirurgia , Estado Pré-Diabético/complicações , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/cirurgia , Prognóstico , Fatores de Risco , Serpinas/sangue , Resultado do Tratamento , Perda de Peso
12.
Obes Surg ; 28(8): 2481-2486, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29532316

RESUMO

OBJECTIVES: Resting energy expenditure (REE) declines more than what is expected according to body composition changes after caloric restriction. This metabolic adaptation is considered one of the factors favoring weight regain. The aim of this study is to evaluate the changes of REE and calculate the degree of metabolic adaptation occurring after laparoscopic sleeve gastrectomy (LSG). METHODS: REE (by indirect calorimetry) and body composition (fat-free mass or FFM, fat mass or FM by bioelectrical impedance analysis) were determined before and after 12 months in 154 patients with obesity treated with laparoscopic sleeve gastrectomy (LSG). RESULTS: Weight loss was 29.8 ± 10.6%, with corresponding relative reductions in FM (44.5 ± 22.8%), FFM (13.7 ± 9.9%), and REE (27.3 ± 12.9%). A predictive equation for REE was computed by using the baseline FFM and FM values to account for body composition changes. A predicted post-weight loss REE was calculated by using this equation and entering post-weight loss body composition values. Observed post-surgery REE was significantly lower than predicted one (1410 ± 312 vs 1611 ± 340 kcal/day, P < 0.001) and metabolic adaptation, calculated as the difference between observed and predicted post-weight loss REE, was - 199 ± 238 kcal/day. The post-surgery level of metabolic adaptation was inversely related to postoperative percent weight loss (r = - 0.170; P < 0.05) and FM loss (r = - 0.245; P < 0.01). CONCLUSIONS: A significant reduction of resting energy expenditure and a significant degree of metabolic adaptation both occur after sleeve gastrectomy. A greater metabolic adaptation could be partly responsible for a lower weight loss after surgery.


Assuntos
Adaptação Fisiológica , Cirurgia Bariátrica/estatística & dados numéricos , Metabolismo Energético , Gastrectomia/estatística & dados numéricos , Obesidade Mórbida/cirurgia , Adulto , Composição Corporal , Restrição Calórica , Calorimetria Indireta , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia , Obesidade Mórbida/metabolismo , Descanso , Perda de Peso
13.
Sci Rep ; 7(1): 17569, 2017 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-29242563

RESUMO

Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance. Notably, CK2 protein-level and activity are greatly up-regulated in white adipose tissue from ob/ob and db/db mice as well as from obese patients, regardless the severity of their insulin-resistance and the presence of pre-diabetes or overt type 2 diabetes. Weight loss obtained by both bariatric surgery or hypocaloric diet reverts CK2 hyper-activation to normal level. Our data suggest a central role of CK2 in insulin-sensitivity, glucose homeostasis and adipose tissue remodeling. CK2 up-regulation is identified as a hallmark of adipose tissue pathological expansion, suggesting a new potential therapeutic target for human obesity.


Assuntos
Adipócitos/patologia , Caseína Quinase II/metabolismo , Insulina/metabolismo , Obesidade/metabolismo , Obesidade/patologia , Transdução de Sinais , Regulação para Cima , Células 3T3-L1 , Tecido Adiposo Branco/patologia , Animais , Transporte Biológico , Glucose/metabolismo , Humanos , Fígado/metabolismo , Camundongos , Músculo Esquelético/metabolismo
14.
Obes Surg ; 27(12): 3179-3186, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28547566

RESUMO

INTRODUCTION: Hypoglycemia is a known adverse event following gastric bypass. The incidence of hypoglycemia after laparoscopic sleeve gastrectomy (LSG) is still under investigation. The aim of our study was to verify the presence of oral glucose tolerance test (OGTT)-related hypoglycemia after LSG and to identify any baseline predictors of its occurrence. METHODS: We analyzed 197 consecutive non-diabetic morbid obese patients that underwent LSG. All patients were studied before and 12 months after LSG. Evaluation included anthropometric parameters, 3-h OGTT for blood glucose (BG), insulin and c-peptide, lipid profile, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), highly sensitive C-reactive protein (hsCRP), and leptin. Hypoglycemia was defined as BG ≤ 2.7 mmol/l. RESULTS: After surgery, 180 patients completed the OGTT. Eleven patients did not complete the test for gastric intolerance, and in six patients, the test was stopped earlier for the onset of severe symptomatic hypoglycemia. Of the patients, 61/186 (32.8%) had at least one OGTT-related hypoglycemia. The highest frequency of hypoglycemic events occurred 150' after glucose load (20.2%). At baseline, patients with hypoglycemic events after surgery (Hypo) were younger (40 ± 11 vs 46 ± 10 years; p < 0.001), less obese (BMI 46 ± 5.7 vs 48.4 ± 7.9 kg/m2; p < 0.05), and had a worse lipid profile as compared to patients without hypoglycemic events (N-Hypo). Moreover, after LSG, Hypo patients compared with N-Hypo presented a higher weight loss (%EBMIL 80 ± 20 vs 62 ± 21%; p < 0.001). Low age, low fasting glucose, and high triglyceride levels before LSG were independent predictors of hypoglycemia development after surgery (r 2 = 0.131). CONCLUSION: These findings confirm the high incidence of post-prandial hypoglycemia 1 year after LSG. Hypoglycemia is more frequent in younger patients with lower fasting glucose and higher triglyceride levels before surgery.


Assuntos
Gastrectomia/efeitos adversos , Hipoglicemia/diagnóstico , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Obesidade Mórbida/cirurgia , Adulto , Glicemia/metabolismo , Jejum/sangue , Feminino , Seguimentos , Gastrectomia/métodos , Teste de Tolerância a Glucose , Humanos , Hipoglicemia/sangue , Incidência , Insulina/sangue , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/epidemiologia , Prognóstico , Fatores de Risco
15.
Endocrine ; 56(3): 521-527, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27530508

RESUMO

Obese patients have been described at increased risk of thrombotic thrombocytopenic purpura, a disease caused by anti-ADAMTS13 autoantibodies. ADAMTS13 has a structure homology with the adipokine thrombospondin-1. We previously demonstrated an increased presence of anti-ADAMTS13 antibodies in obese patients. We aimed to study the changes induced by weight loss after bariatric surgery on some inflammatory and coagulative parameters and their link with anti-ADAMTS13 autoantibodies. We studied 100 obese patients before and after weight loss induced by bariatric surgery and 79 lean volunteers as controls. We measured anthropometric, metabolic and inflammatory parameters, thrombospondin-1, ADAMTS13 activity, anti-ADAMTS13 autoantibodies, Von Willebrand factor. At baseline, 13 % of patients was positive for anti-ADAMTS13 autoantibodies, while all controls were negative. Thrombospondin-1 levels were higher in obese subjects with than without antibodies, with a positive correlation between the two parameters. In multiple logistic regression analysis only thrombospondin-1 levels predicted positivity for anti-ADAMTS13 antibodies. After weight loss both anti-ADAMTS13 antibodies and thrombospondin-1 reduced significantly. Weight loss in obesity improves the inflammatory and coagulative profile, and in particular anti-ADAMTS13 autoantibodies, ADAMTS13 activity and thrombospondin-1.


Assuntos
Proteína ADAMTS13/imunologia , Autoanticorpos/sangue , Coagulação Sanguínea/fisiologia , Inflamação/imunologia , Obesidade/imunologia , Perda de Peso/fisiologia , Adulto , Feminino , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue
16.
J Clin Endocrinol Metab ; 101(10): 3600-3607, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27336358

RESUMO

CONTEXT: Postprandial hypoglycemia (PPHG) is a recognized complication of Roux-en-Y gastric bypass (RYGB) surgery. Data on PPHG after laparoscopic sleeve gastrectomy (LSG) are scant. OBJECTIVE: The objective of the study was to identify preoperative predictors of PPHG in subjects spontaneously self-reporting PPHG after RYGB or LSG. Patients, Setting, and Intervention: Nondiabetic patients spontaneously self-reporting symptoms/signs of PPHG (PPHG group, 21 RYGB and 11 LSG) were compared in a case-control design with subjects who never experienced spontaneous or oral glucose tolerance test (OGTT)-induced hypoglycemia over 24 months after surgery (No-PPHG group, 13 RYGB and 40 LSG). Paired pre- and postoperative 3-hour OGTTs were analyzed in all participants. MAIN OUTCOME MEASURES: Insulin sensitivity was assessed by the oral glucose insulin sensitivity index and ß-cell function by mathematical modeling of the C-peptide response to glucose. RESULTS: Before surgery, the body mass index was lower in PPHG than No-PPHG patients in the RYGB (P = .002) and trended similarly in the LSG group (P = .08). Fasting glycemia and the glucose-OGTT nadir were lower in the PPHG than the No-PPHG subjects in both surgery groups. Before surgery, insulin sensitivity was higher in PPHG than No-PPHG in the RYGB (393 ± 55 vs 325 ± 44 mL/min-1 · m-2, P = .001) and LSG groups (380 ± 48 vs 339 ± 60 mL/min-1 · m-2, P = .05) and improved to a similar extent in all groups after surgery. Before surgery, ß-cell glucose sensitivity was higher in PPHG than No-PPHG in both RYGB (118 ± 67 vs 65 ± 24 pmol/min-1 · m2 · mM-1) and LSG patients (114 ± 32 vs 86 ± 33) (both P = .02) and improved in all subjects after surgery. CONCLUSIONS: In subjects self-reporting PPHG after surgery, lower presurgery plasma glucose concentrations, higher insulin sensitivity, and better ß-cell glucose sensitivity are significant predictors of PPHG after both RYGB and LSG.


Assuntos
Cirurgia Bariátrica/efeitos adversos , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Obesidade/cirurgia , Avaliação de Resultados em Cuidados de Saúde , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hipoglicemia/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Autorrelato
17.
Diabetes ; 63(8): 2800-11, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24622799

RESUMO

Insulin resistance and obesity are associated with a reduction of mitochondrial content in various tissues of mammals. Moreover, a reduced nitric oxide (NO) bioavailability impairs several cellular functions, including mitochondrial biogenesis and insulin-stimulated glucose uptake, two important mechanisms of body adaptation in response to physical exercise. Although these mechanisms have been thoroughly investigated in skeletal muscle and heart, few studies have focused on the effects of exercise on mitochondria and glucose metabolism in adipose tissue. In this study, we compared the in vivo effects of chronic exercise in subcutaneous adipose tissue of wild-type (WT) and endothelial NO synthase (eNOS) knockout (eNOS(-/-)) mice after a swim training period. We then investigated the in vitro effects of NO on mouse 3T3-L1 and human subcutaneous adipose tissue-derived adipocytes after a chronic treatment with an NO donor: diethylenetriamine-NO (DETA-NO). We observed that swim training increases mitochondrial biogenesis, mitochondrial DNA content, and glucose uptake in subcutaneous adipose tissue of WT but not eNOS(-/-) mice. Furthermore, we observed that DETA-NO promotes mitochondrial biogenesis and elongation, glucose uptake, and GLUT4 translocation in cultured murine and human adipocytes. These results point to the crucial role of the eNOS-derived NO in the metabolic adaptation of subcutaneous adipose tissue to exercise training.


Assuntos
Tecido Adiposo/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Glucose/metabolismo , Mitocôndrias/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Condicionamento Físico Animal/fisiologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Linhagem Celular , Humanos , Masculino , Camundongos , Camundongos Knockout , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Norepinefrina , Natação
18.
Eur J Haematol ; 92(6): 497-501, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24460705

RESUMO

OBJECTIVES: Thrombotic thrombocytopenic purpura (TTP) is a rare and devastating hematologic disorder frequently associated with multiple organ failure and sometimes death. This syndrome is mainly associated with severe deficiency of ADAMTS13, a disintegrin and metalloprotease with thrombospondin (TSP)-1 repeats, cleaving high molecular weight von Willebrand Factor (ULVWF) multimers. Decreased plasma ADAMTS13 activity results in the accumulation of ULVWF multimers with consequent platelet activation. Recently, obesity has been considered as a potential independent risk factor for TTP, but the reason of this association is still unknown. METHODS AND RESULTS: We describe an unusual case of fatal recurrent TTP in a morbid obese female with non-alcoholic steatohepatitis (NASH) and severe ADAMTS13 activity deficiency due neither to an inhibitory autoantibody nor to a gene mutation. CONCLUSIONS: Visceral obesity is associated with non-alcoholic fatty liver disease (NAFLD) and NASH: we hypothesized that these conditions can influence ADAMTS13 antigen and activity. In fact, hepatic stellate cells (HSC) are the main producers of ADAMTS13, and a decrease in ADAMTS13 activity has been reported in liver disease.


Assuntos
Proteínas ADAM/deficiência , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Púrpura Trombocitopênica Trombótica/complicações , Proteínas ADAM/genética , Proteínas ADAM/imunologia , Proteínas ADAM/metabolismo , Proteína ADAMTS13 , Adulto , Ativação Enzimática , Evolução Fatal , Feminino , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Contagem de Plaquetas , Púrpura Trombocitopênica Trombótica/diagnóstico
19.
Am J Physiol Endocrinol Metab ; 306(5): E519-28, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24381004

RESUMO

Endurance exercise training increases cardiac energy metabolism through poorly understood mechanisms. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) in cardiomyocytes contributes to cardiac adaptation. Here we demonstrate that the NO donor diethylenetriamine-NO (DETA-NO) activated mitochondrial biogenesis and function, as assessed by upregulated peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (Tfam) expression, and by increased mitochondrial DNA content and citrate synthase activity in primary mouse cardiomyocytes. DETA-NO also induced mitochondrial biogenesis and function and enhanced both basal and insulin-stimulated glucose uptake in HL-1 cardiomyocytes. The DETA-NO-mediated effects were suppressed by either PGC-1α or Tfam small-interference RNA in HL-1 cardiomyocytes. Wild-type and eNOS(-/-) mice were subjected to 6 wk graduated swim training. We found that eNOS expression, mitochondrial biogenesis, mitochondrial volume density and number, and both basal and insulin-stimulated glucose uptake were increased in left ventricles of swim-trained wild-type mice. On the contrary, the genetic deletion of eNOS prevented all these adaptive phenomena. Our findings demonstrate that exercise training promotes eNOS-dependent mitochondrial biogenesis in heart, which behaves as an essential step in cardiac glucose transport.


Assuntos
Adaptação Fisiológica/fisiologia , Metabolismo dos Carboidratos/fisiologia , Glucose/metabolismo , Renovação Mitocondrial/fisiologia , Miocárdio/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Condicionamento Físico Animal/fisiologia , Adaptação Fisiológica/efeitos dos fármacos , Animais , Metabolismo dos Carboidratos/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Coração/efeitos dos fármacos , Proteínas de Grupo de Alta Mobilidade/genética , Proteínas de Grupo de Alta Mobilidade/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Renovação Mitocondrial/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Fator 1 Nuclear Respiratório/genética , Fator 1 Nuclear Respiratório/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triazenos/farmacologia
20.
Eur J Clin Invest ; 42(11): 1197-204, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22957496

RESUMO

BACKGROUND: The low-grade chronic inflammation present in obesity has been recognized as a risk factor for thrombosis, atherosclerosis and cardiovascular complications. In this context, production by adipose organ of a number of inflammatory adipokines could play a crucial role. It has been reported that obesity represents a risk factor for acquired thrombotic thrombocytopenic purpura (TTP), a disease caused by ADAMTS13 deficiency because of anti-ADAMTS13 antibodies, but the pathophysiological link between obesity and TTP is still unknown. We aimed to investigate mechanisms linking obesity to risk of TTP. MATERIALS AND METHODS: Eighty obese patients consecutively admitted to Bariatric Unit of Padua between 2006 and 2009, and 39 lean subjects were characterized by anthropometric, metabolic and inflammatory parameters. ADAMTS13 autoantibodies, activity and antigen levels, and several cytokines including thrombospondin-1 were measured. RESULTS: 21.3% of obese patients were positive for noninhibitory ADAMTS13 autoantibodies, while all lean subjects were negative (P<0.01). No differences in ADAMTS13 activity and antigen levels were found. Thrombospondin-1 levels were significantly higher in obese than in lean subjects (974.4 ± 592.7 vs. 318.9 ± 202.1 ng/mL; P<0.001) and were inversely correlated with ADAMTS13 activity (R=-0.4853; P<0.001). Dot blot suggests that anti-ADAMTS13 antibodies in obese patients bind recombinant thrombospondin-1. CONCLUSIONS: We suggest that anti-ADAMTS13 antibodies are directed against thrombospondin domains shared between ADAMTS13 and thrombospondin-1 and that their generation may be sustained by high levels of thrombospondin-1. This phenomenon could be of relevance, because little is known on the pathogenesis of TTP and its possible link with obesity.


Assuntos
Proteínas ADAM/sangue , Autoanticorpos/sangue , Obesidade/imunologia , Púrpura Trombocitopênica Trombótica/imunologia , Trombospondina 1/sangue , Proteínas ADAM/deficiência , Proteínas ADAM/imunologia , Adiponectina/sangue , Adiponectina/metabolismo , Adulto , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Púrpura Trombocitopênica Trombótica/metabolismo , Risco , Trombospondina 1/metabolismo , Perda de Peso/imunologia , Perda de Peso/fisiologia
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