ROSA TSUNECHIRO FUKUI

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LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina

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Autor: SANTOS, Rosa Ferreira dos ×

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  • article 16 Citação(ões) na Scopus
    TCF7L2 correlation in both insulin secretion and postprandial insulin sensitivity
    (2018) FERREIRA, Mari Cassol; SILVA, Maria Elizabeth Rossi da; FUKUI, Rosa Tsuneshiro; ARRUDA-MARQUES, Maria do Carmo; SANTOS, Rosa Ferreira dos
    Background: The TCF7L2 rs7903146 variant is strongly associated with type 2 diabetes mellitus (T2DM). However, the mechanisms involved in this association remain unknown and may include extrapancreatic effects. The aim of this study was to perform a metabolic characterization of T2DM patients with and without the TCF7L2 rs7903146 risk T allele and analyze some influences of the TCF7L2 genotype on glucose metabolism. Methods: Patients with T2DM (n = 162) were genotyped for the TCF7L2 rs7903146 single nucleotide polymorphism. Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C, HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon. Additional secondary assessments included determination of insulinogenic index (IGI(30)), and insulin sensitivity (%S) and resistance (IR) by Homeostatic model assessment (HOMA). Results: Patients with the CT/TT genotype showed lower baseline plasma concentrations of C-peptide when compared with those with the CC genotype. Of the 56 individuals who participated in the mixed-meal test, 26 and 30 had the CC and CT/TT genotypes, respectively. CT/TT subjects, compared with CC individuals, had higher post prandial plasma levels of insulin and C-peptide at 30-120 min (p < 0.05) and proinsulin at 45-240 min (p < 0.05). Interestingly CT/TT individuals presented at baseline higher % S (p = 0.021), and lower IR (p = 0.020) than CC individuals. No significant differences in IGI(30) values were observed between groups. Conclusions: The T2DM individuals carrying the rs7903146 T allele of the TCF7L2 gene presented higher IR pattern in response to a mix-meal test, different of beta cell function at baseline assessed by C-peptide levels which was lower, and Homa-IR was lower when comparing with non-carriers.
  • article 21 Citação(ões) na Scopus
    Left ventricular diastolic function in patients with type 2 diabetes treated with a dipeptidyl peptidase-4 inhibitor- a pilot study
    (2014) NOGUEIRA, Katia Camarano; FURTADO, Meive; FUKUI, Rosa Tsuneshiro; CORREIA, Marcia Regina Silva; SANTOS, Rosa Ferreira dos; ANDRADE, Jose Lazaro; SILVA, Maria Elizabeth Rossi da
    Background: Blood glucose control is fundamental albeit not enough to prevent diabetic macrovascular complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in improving metabolic parameters in patients with type 2 diabetes mellitus (T2DM) but little is known about its cardiovascular effects. We compared the DPP-4 inhibitor sitagliptin with bedtime NPH insulin (NPH) as add-on therapy in patients with T2DM, aiming to ascertain which drug would have additional cardioprotective effects. Methods: Thirty-five T2DM patients inadequately controlled with metformin plus glyburide were randomized to receive sitagliptin (n = 18) or NPH (n = 17) for 24 weeks. Fasting plasma glucose, HbA1c, lipid profile, C-reactive protein, active glucagon-like peptide (aGLP-1) levels, 24-hour ambulatory blood pressure measurement and comprehensive 2-dimensional echocardiogram were determined before and after treatments. Results: Both sitagliptin and NPH therapies decreased HbA1c levels after 24 weeks. Fasting plasma glucose and triglyceride levels decreased in the NPH group whereas only sitagliptin increased aGLP-1 levels. Left ventricular diastolic dysfunction (LVDD) was detected in 58.6% of twenty-nine patients evaluated. Beneficial effects in LVDD were observed in 75% and 11% of patients treated with sitagliptin and NPH, respectively (p = 0.015). Neither therapy changed C-reactive protein or blood pressure. Conclusions: Sitagliptin and bedtime NPH were similarly effective on glucose control. Improvement in LVDD in T2DM patients treated with sitagliptin was suggested, probably related to the increase of aGLP-1 levels. Therefore, DPP-4 inhibitor seems to have cardioprotective effects independent of glucose control and may have a role in the prevention of diabetic cardiomyopathy.
  • article 19 Citação(ões) na Scopus
    Effect of TCF7L2 polymorphism on pancreatic hormones after exenatide in type 2 diabetes
    (2019) FERREIRA, Mari Cassol; SILVA, Maria Elizabeth Rossi da; FUKUI, Rosa Tsuneshiro; ARRUDA-MARQUES, Maria do Carmo; AZHAR, Salman; SANTOS, Rosa Ferreira dos
    BackgroundGlucagon-like peptide 1 (GLP-1) stimulates insulin secretion and reduces blood glucose in type 2 diabetes mellitus (T2DM). TCF7L2 rs7903146 polymorphism has been associated with decreased insulin secretion, reduced GLP-1 action, and possible impaired peripheral insulin sensitivity.ObjectivesTo evaluate the postprandial pancreatic hormone response in patients with T2DM carriers of the TCF7L2 variant rs7903146 (CT/TT) compared with noncarriers of this variant (CC) after treatment with the GLP-1 agonist exenatide.MethodsIntervention study. Patients with T2DM (n=162) were genotyped for the TCF7L2 rs7903146 single nucleotide polymorphism (SNP). Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C (HbA1c), HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon before and after treatment with exenatide for 8weeks.ResultsPatients with genotypes CC and CT/TT presented similar glucose area under the curve (AUC) 0-180min before treatment and a similar decrease after treatment (p<0.001). Before exenatide, insulin levels at 30-120min were higher in CT/TT versus CC subjects (p<0.05). After treatment with exenatide, only CT/TT individuals demonstrated insulin reduction at 30-180 min during the meal test (p<0.05). Patients with the CC genotype presented no differences in insulin concentrations before and after treatment. The areas under the glucagon curve between 0 and 180min were similar before treatment and reduced after treatment in both groups (p<0.001).ConclusionsThe presence of the TCF7L2 rs7903146 T allele in patients with T2DM was associated with increased secretion of insulin response to a mixed-meal test. Furthermore, after treatment with exenatide, only the carriers of the T allele showed significantly decreased postprandial plasma insulin peak levels comparing with non carriers.
  • article 17 Citação(ões) na Scopus
    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 da
    OBJECTIVE: 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.
  • article 1 Citação(ões) na Scopus
    Short and Long Term Effects of a DPP-4 Inhibitor Versus Bedtime NPH Insulin as ADD-ON Therapy in Patients with Type 2 Diabetes
    (2016) SILVA, Giordana Maluf da; NOGUEIRA, Katia Camarano; FUKUI, Rosa Tsuneshiro; CORREIA, Marcia Regina Soares; SANTOS, Rosa Ferreira dos; SILVA, Maria Elizabeth Rossi da
    Background: We conducted a comparison between the dipeptidyl-peptidase-4(DPP-4) inhibitor sitagliptin versus NPH insulin as an add-on therapies in patients with type 2 diabetes mellitus (T2D) failing oral medications. The objective was to ascertain the better indication in long-duration diabetes. Methods: thirty-five T2D patients inadequately controlled with metformin plus glyburide were randomized to receive sitagliptin (n=18) or bedtime NPH insulin (n=17) for 12 months. HbA1c levels and a metabolic and hormonal profile at fasting and post-meal (every 30 minutes for 4 hours) were evaluated before and after 6 months (short-term) and 12 months (long-term) after adding sitagliptin or bedtime NPH insulin to their drug regime. Results: Sitagliptin and NPH insulin decreased HbA1c levels equally after 6 months (p<0.001) with no further improvement after 12 months: sitagliptin (8.1 +/- 0.7% vs. 7.3 +/- 0.8% vs. 7.4 +/- 1.9%) and insulin (8.1 +/- 0.6% vs. 7.3 +/- 0.7% vs. 7.2 +/- 1.0%). Fasting glucose, fasting and postprandial triglyceride and C-peptide levels were also reduced by NPH insulin whereas postprandial insulin was decreased by sitagliptin. Body weight and postchallenge free fatty acid levels increased with insulin treatment. The transitory suppression (at 6 months) of postprandial proinsulin levels with both therapies, and of glucagon with sitagliptin, was followed by values similar or worse to those at pre-treatment. Conclusion: The use of either NPH insulin or a DPP-4 inhibitor as add-on treatments improves glucose control in patients with T2D failing on metformin plus glyburide therapy. The results were not attributed to a permanent improvement in alpha or beta cell function in patients with long-duration diabetes.
  • article 5 Citação(ões) na Scopus
    Effects of nateglinide and rosiglitazone on pancreatic alpha- and beta-cells, GLP-1 secretion and inflammatory markers in patients with type 2 diabetes: randomized crossover clinical study
    (2016) TOSTES, Glauce Cordeiro Ulhoa; CUNHA, Maria Rosario; FUKUI, Rosa Tsumeshiro; CORREIA, Marcia Regina Silva; ROCHA, Dalva Marreiro; SANTOS, Rosa Ferreira dos; SILVA, Maria Elizabeth Rossi da
    Background: To compare the effects of nateglinide and rosiglitazone on inflammatory markers, GLP-1 levels and metabolic profile in patients with type 2 diabetes (DM2). Methods: A prospective study was performed in 20 patients with DM2, mean age 51.82 +/- 8.05 years, previously treated with dietary intervention. Participants were randomized into rosiglitazone (4-8 mg/day) or nateglinide (120 mg 3 times a day) therapy. After 4 months, the patients were crossed-over with 8 weeks washout period to the alternative treatment for an additional 4-month period on similar dosage schedule. The following variables were assessed before and after 4 months of each treatment period: (1) a test with a standardized 500 calories meal for 5 h including frequent measurements of glucose, insulin, glucagon, proinsulin, GLP-1, free fat acids (FFA), and triglycerides levels was obtained. The lipid profile and HbA1 levels were measured at fasting. (2) Haemostatic and inflammatory markers: platelet aggregation, fibrinogen, PAI-1 activity, C reactive protein (CRP), IL-6, TNF-alpha, leptin, sICAM and TGF beta levels. Results: Both therapy decreased blood glucose levels under the postprandial curve but neither affected glucagon and GLP-1 levels. Nateglinide was associated with higher insulin and pro-insulin secretion, but similar pro-insulin/insulin ratio when compared with rosiglitazone. Only rosiglitazone decreased Homa beta, PAI-1 activity, CRP, fibrinogen, TGF beta, FFA and triglyceride levels. Conclusions: Nateglinide and rosiglitazone were effective in improving glucose and lipid profile and beta cell function, but rosiglitazone afforded a better anti-inflammatory effect. No drug restored alpha cell sensitivity or changed GLP-1 levels. Maintenance of haemostatic factors, inflammatory factors and glucagon levels can be related to the continuously worsening of cardiovascular function and glucose control observed in DM2.