BERNARDO LEO WAJCHENBERG
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina
LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina
17 resultados
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- Plasma kinetics of an LDL-like nanoemulsion and lipid transfer to HDL in subjects with glucose intolerance(2012) BERTATO, Marina P.; OLIVEIRA, Carolina P.; WAJCHENBERG, Bernardo L.; LERARIO, Antonio C.; MARANHAO, Raul C.OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with C-14-cholesteryl ester and H-3-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14 C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the H-3-free- cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic signaling.
- Development and internal validation of an adrenal cortical carcinoma prognostic score for predicting the risk of metastasis and local recurrence(2013) FREIRE, Daniel Soares; SIQUEIRA, Sheila Aparecida Coelho; ZERBINI, Maria Claudia Nogueira; WAJCHENBERG, Bernardo Leo; CORREA-GIANNELLA, Maria Lucia; LUCON, Antonio Marmo; PEREIRA, Maria Adelaide AlbergariaObjective To develop and internally validate a prognostic score to predict the risk of metastases or recurrence in patients with adrenal cortical carcinomas (ACC). Design Clinical, laboratory and pathological data from 129 ACC patients, treated in a tertiary centre, were retrospectively reviewed. Results Using a multivariate binary logistic regression analysis, we developed a prognostic score with five covariates: a functional pattern other than isolated hyperandrogenism, a tumour size >75cm, a primary tumour classified as T3/T4, the presence of microscopic venous invasion and a mitotic index >5/50 high-power fields. The prognostic score was calibrated according to the Hosmer-Lemeshow goodness-of-fit test (P=09329) and exhibited excellent overall performance (Brier score=00738). Finally, the discriminatory ability of the model, determined by the area under the ROC curve (A(ROC)), was near perfect (A(ROC), 09611; 95% CI, 092676-099552). The prediction model was internally validated with 200 bootstrap resamples and achieved excellent performance for estimating the risk of metastasis and recurrence in eight additional patients with apparently localized disease at diagnosis. Conclusion We developed and internally validated a prognostic score based on the clinicopathological data that are readily available to any attending physician. Our model can be used to accurately estimate the risk of unfavourable outcomes in ACC patients. This score could be beneficial for both patient counselling and the identification of patients in whom adjuvant mitotane is justified.
conferenceObject Yield of Different Approaches for Screening for Cardiovascular Disease in Asymptomatic Diabetics(2014) CHURCHILL, Timothy W.; RASSI, Carlos H.; TAVARES, Carlos A. Fernandes; FAHEL, Mateus G.; RASSI, Fabricia P.; UCHIDA, Augusto H.; WAJCHENBERG, Bernardo L.; LERARIO, Antonio C.; HULTEN, Edward; BITTENCOURT, Marcio S.; BLANKSTEIN, Ron- Effects of Gastric Bypass Surgery in Patients With Type 2 Diabetes and Only Mild Obesity(2012) COHEN, Ricardo V.; PINHEIRO, Jose C.; SCHIAVON, Carlos A.; SALLES, Joao E.; WAJCHENBERG, Bernardo L.; CUMMINGS, David E.OBJECTIVE-Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes in severely obese patients through mechanisms beyond just weight loss, and it may benefit less obese diabetic patients. We determined the long-term impact of RYGB on patients with diabetes and only class 1 obesity. RESEARCH DESIGN AND METHODS-Sixty-six consecutively selected diabetic patients with BMI 30-35 kg/m(2) underwent RYGB in a tertiary-care hospital and were prospectively studied for up to 6 years (median 5 years [range 1-6]), with 100% follow-up. Main outcome measures were safety and the percentage of patients experiencing diabetes remission (HbA(1c) <6.5% without diabetes medication). RESULTS-Participants had severe, longstanding diabetes, with disease duration 12.5 +/- 7.4 years and HbA(1c) 9.7 +/- 1.5%, despite insulin and/or oral diabetes medication usage in everyone. For up to 6 years following RYGB, durable diabetes remission occurred in 88% of cases, with glycemic improvement in 11%. Mean HbA(1c) fell from 9.7 +/- 1.5 to 5.9 +/- 0.1% (P < 0.001), despite diabetes medication cessation in the majority. Weight loss failed to correlate with several measures of improved glucose homeostasis, consistent with weight-independent antidiabetes mechanisms of RYGB. C-peptide responses to glucose increased substantially, suggesting improved beta-cell function. There was no mortality, major surgical morbidity, or excessive weight loss. Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke. CONCLUSIONS-This is the largest, longest-term study examining RYGB for diabetic patients without severe obesity. RYGB safely and effectively ameliorated diabetes and associated comorbidities, reducing cardiovascular risk, in patients with a BMI of only 30-35 kg/m(2).
- Association between Pro12Ala, Pvull, Avall, Sstl and ADIPOQ Single-Nucleotide Polymorphisms with Lipid and Glycemic Profiles of Patients with Berardinelli-Seip Syndrome(2014) BARACHO, Maria F. P.; NUNES, Adriana B.; HIRATA, Mario H.; HIRATA, Rosario D. C.; FAJARDO, Christina M.; SANTOS, Maria G. N.; WAJCHENBERG, Bernardo L.; MARCO, Luiz A. De; BRANDAO-NETO, JoseBackground/Aims: Berardinelli-Seip syndrome (BSS) is a recessive autosomal genetic disorder characterized by the near loss of adipose tissue with disturbance in lipid metabolism. Methods: Biochemical and hormonal parameters and Pro12Ala, Pvull, Avall, Sstl and ADIPOQ polymorphisms in 22 patients with BSS were analyzed and examined for a possible association with lipid profiles. Results: Parental consanguinity, insulin resistance and diabetes mellitus were observed in 63.6, 81.8 and 59.1% of patients, respectively. All individuals presented high triglyceride levels, and 68.1% of patients showed high cholesterol levels. The Pro/Pro genotype of the Pro12Ala polymorphism of the PPAR gamma 2 gene was found in 86.3% of patients; the Ala/Ala variant was not observed in any patient. The PvuII polymorphism of the LPL gene showed a frequency of 50% for the P1P2 variant. The AvaII polymorphism of the LDLR gene showed a similar frequency of 40.9% for both CT and TT variants. The S1S1 genotype of the Sstl polymorphism of the APOC3 gene had a frequency of 86.3%. The CC allele of the ADIPOQ polymorphism of the adiponectin gene was found in 54.6% of patients. Conclusions: No association was found between lipid parameters and the relevant Pvull, Avall and Sstl polymorphisms. However, we did observe an association of the Pro12Ala and ADIPOQ polymorphisms with higher lipid levels, suggesting a close relationship between these factors. (C) 2014 S. Karger AG, Basel
- Lipoprotein metabolism in patients with type 1 diabetes under intensive insulin treatment(2013) FEITOSA, Alina C. R.; FEITOSA-FILHO, Gilson S.; FREITAS, Fatima R.; WAJCHENBERG, Bernardo L.; MARANHAO, Raul C.Background: Type 1 diabetes (T1DM) is frequently accompanied by dyslipidemia related with insulin-dependent steps of the intravascular lipoprotein metabolism. T1DM dyslipidemia may predispose to precocious cardiovascular disease and the lipid status in T1DM under intensive insulin treatment has not been sufficiently explored. The aim was to investigate the plasma lipids and the metabolism of LDL and HDL in insulin-treated T1DM patients with high glycemic levels. Methods: Sixteen male patients with T1DM (26 +/- 7 yrs) with glycated hemoglobin >7%, and 15 control subjects (28 +/- 6 yrs) were injected with a lipid nanoemulsion (LDE) resembling LDL and labeled with C-14-cholesteryl ester and H-3-free-cholesterol for determination of fractional clearance rates (FCR, in h(-1)) and cholesterol esterification kinetics. Transfer of labeled lipids from LDE to HDL was assayed in vitro. Results: LDL-cholesterol (83 +/- 15 vs 100 +/- 29 mg/dl, p=0.08) tended to be lower in T1DM than in controls; HDL-cholesterol and triglycerides were equal. LDE marker C-14-cholesteryl ester was removed faster from plasma in T1DM patients than in controls (FCR=0.059 +/- 0.022 vs 0.039 +/- 0.022h-1, p=0.019), which may account for their lower LDL-cholesterol levels. Cholesterol esterification kinetics and transfer of non-esterified and esterified cholesterol, phospholipids and triglycerides from LDE to HDL were also equal. Conclusion: T1DM patients under intensive insulin treatment but with poor glycemic control had lower LDL-cholesterol with higher LDE plasma clearance, indicating that LDL plasma removal was even more efficient than in controls. Furthermore, HDL-cholesterol and triglycerides, cholesterol esterification and transfer of lipids to HDL, an important step in reverse cholesterol transport, were all normal. Coexistence of high glycemia levels with normal intravascular lipid metabolism may be related to differences in exogenous insulin bioavailabity and different insulin mechanisms of action on glucose and lipids. Those findings may have important implications for prevention of macrovascular disease by intensive insulin treatment.
- Relationship between glycemic control and coronary artery disease severity, prevalence and plaque characteristics by computed tomography coronary angiography in asymptomatic type 2 diabetic patients(2016) TAVARES, C. A. F.; RASSI, C. H. R. E.; FAHEL, M. G.; WAJCHENBERG, B. L.; ROCHITTE, C. E.; LERARIO, A. C.Evaluate whether glycemic control in type 2 diabetes (DM2) asymptomatic for coronary artery disease (CAD) affects not only the presence and magnitude of CAD but also the characteristics of plaque vulnerability using multidetector row computed coronary tomography (MDCT). Acute coronary syndrome (ACS) is frequently observed in asymptomatic DM2 patients. Positive vessel remodeling (PR) and low-attenuation plaques (LAP) identified by MDCT have been demonstrated to be characteristics of subsequent culprit lesions of ACS. However, little is known regarding plaque characteristics in asymptomatic diabetic patients and their relationship with glycemic control. Ninety asymptomatic DM2 patients, aged 40-65 years old, underwent MDCT. The presence of atherosclerotic obstruction, defined as coronary stenosis aeyen50 %, and plaque characteristics were compared between two groups of patients with A1c < 7 and A1c aeyenaEuroe7 %. Of the 90 patients, 38 (42.2 %) presented with coronary atherosclerotic plaques, 11 had A1c < 7 % and 27 had A1c aeyenaEuroe7 % (p = 0.0006). Fourteen patients had significant lumen obstruction higher than 50 %: 3 in the A1c < 7 % group and 11 in the A1c aeyenaEuroe7 % group (p = 0.02). Non-calcified plaque was more prevalent in the A1c aeyenaEuroe7 % group (p = 0.005). In eleven patients, the simultaneous presence of two vulnerability plaque characteristics (PR and LAP) were observed more frequently in the A1c aeyenaEuroe7 group (n = 8) than in the A1c < 7 group (n = 3) (p = 0.04). Asymptomatic DM2 patients with A1c aeyenaEuroe7 % have a higher frequency of CAD and a higher proportion of vulnerable atherosclerotic coronary plaque by MDCT compared to patients with DM2 with A1c < 7 in our study.
- LIRAGLUTIDE: NEW RESULTS IN THE TREATMENT OF TYPE 2 DIABETES MELLITUS(2012) MATEOS, J. L.; WAJCHENBERG, B. L.New drugs for type 2 diabetes that act on incretin metabolism have been shown to improve glycemic control, reduce body weight and have a low risk for hypoglycemia. Among these, liraglutide is the first glucagon-like peptide 1 (GLP-1) analogue approved for subcutaneous, once-daily administration. According to results from clinical trials, liraglutide is on attractive alternative for the early treatment of type 2 diabetes. The results of the LEAD (Liraglutide Effect and Action in Diabetes) study program demonstrated the efficacy and safety of liraglutide in terms of reduction of glycated hemoglobin (HbA(tc)) levels, significant loss of body weight that was maintained over the long term, better control of the lipid profile and systolic arterial pressure, reduction of the risk for hypoglycemia and reduction of cardiovascular risk. Moreover, the drug was demonstrated to be safe and can be co-administered with oral antidiabetic agents. The product's tolerability has been demonstrated, with nausea as the most common adverse event, which waned from the fourth week of treatment.
- Metformin, but not glimepiride, improves carotid artery diameter and blood flow in patients with type 2 diabetes mellitus(2012) MACHADO, Helena Atroch; VIEIRA, Marcelo; CUNHA, Maria Rosaria; CORREIA, Marcia Regina Soares; FUKUI, Rosa Tsunechiro; SANTOS, Rosa Ferreira dos; ROCHA, Dalva Marreiro; WAJCHENBERG, Bernardo Leo; LAGE, Silvia G.; SILVA, Maria Elizabeth Rossi daOBJECTIVE: To compare the effects of glimepiride and metformin on vascular reactivity, hemostatic factors and glucose and lipid profiles in patients with type 2 diabetes. METHODS: A prospective study was performed in 16 uncontrolled patients with diabetes previously treated with dietary intervention. The participants were randomized into metformin or glimepiride therapy groups. After four months, the patients were crossed over with no washout period to the alternative treatment for an additional four-month period on similar dosage schedules. The following variables were assessed before and after four months of each treatment: 1) fasting glycemia, insulin, catecholamines, lipid profiles and HbA(1) levels; 2) t-PA and PAI-1 (antigen and activity), platelet aggregation and fibrinogen and plasminogen levels; and 3) the flow indices of the carotid and brachial arteries. In addition, at the end of each period, a 12-hour metabolic profile was obtained after fasting and every 2 hours thereafter. RESULTS: Both therapies resulted in similar decreases in fasting glucose, triglyceride and norepinephrine levels, and they increased the fibrinolytic factor plasminogen but decreased t-PA activity. Metformin caused lower insulin and pro-insulin levels and higher glucagon levels and increased systolic carotid diameter and blood flow. Neither metformin nor glimepiride affected endothelial-dependent or endothelial-independent vasodilation of the brachial artery. CONCLUSIONS: Glimepiride and metformin were effective in improving glucose and lipid profiles and norepinephrine levels. Metformin afforded more protection against macrovascular diabetes complications, increased systolic carotid artery diameter and total and systolic blood flow, and decreased insulin levels. As both therapies increased plasminogen levels but reduced t-PA activity, a coagulation process was likely still ongoing.
- Clinical approaches to preserving β-cell function in diabetes(2015) WAJCHENBERG, B. L.; CARVALHO, R. M. DeIn type 2 diabetes (DM2) there is progressive deterioration of β-cell function and mass. It was found that islet function was about 50% of normal at the time of diagnosis and there was a reduction of β-cell mass of about 60% at necropsy (accelerated apoptosis). Among the interventions to preserve the β-cells, those that lead to short-term improvement of β-cell secretion are weight loss, metformin, sulfonylureas, and insulin. Long-term improvement was demonstrated with short-term insulin therapy of newly diagnosed DM2. Besides, long-term intensive insulin therapy plus metformin or triple oral therapy (metformin + glyburide + pioglitazone) for 3.5 years enabled β-cell function to be preserved for at least that period of time. Furthermore, long-term improvement was also shown with the isolated use of anti-apoptotic drugs such as glitazones, and the use of glucagon-like peptide-1 receptor agonists (GLP-1 mimetics), not inactivated by the enzyme dipeptidyl peptidase-4, and/or to inhibit that enzyme (GLP-1 enhancers). The incretin hormones are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas and overall maintenance of glucose homeostasis. Of the incretins, only GLP-1 mimetics or enhancers can be used for the treatment of DM2. Although incretin-based medications maintain β-cell function, there is no evidence that they increase β-cell mass. © Springer Science+Business Media Dordrecht 2010, 2015.