ROSA TSUNECHIRO FUKUI

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

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  • conferenceObject
    Evaluation of the Profile of Circulating microRNAs in Individuals with Recent Type 1 Diabetes and Healthy Controls
    (2017) SANTOS, Aritania S.; FERREIRA, Ludmila R.; FUKUI, Rosa T.; CUNHA-NETO, Edecio; SILVA, Maria Elizabeth R.
  • 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 23 Citação(ões) na Scopus
    The influence of population stratification on genetic markers associated with type 1 diabetes
    (2017) GOMES, Karla Fabiana Brasil; SANTOS, Aritania Sousa; SEMZEZEM, Cintia; CORREIA, Marcia Regina; BRITO, Luciano Abreu; RUIZ, Marcelo Ortega; FUKUI, Rosa Tsuneshiro; MATIOLI, Sergio Russo; PASSOS-BUENO, Maria Rita; SILVA, Maria Elizabeth Rossi da
    Ethnic admixtures may interfere with the definition of type 1 diabetes (T1D) risk determinants. The role of HLA, PTPN22, INS-VNTR, and CTLA4 in T1D predisposition was analyzed in Brazilian T1D patients (n = 915), with 81.7% self-reporting as white and 789 controls (65.6% white). The results were corrected for population stratification by genotyping 93 ancestry informative markers (AIMs) (BeadXpress platform). Ancestry composition and structural association were characterized using Structure 2.3 and STRAT. Ethnic diversity resulted in T1D determinants that were partially discordant from those reported in Caucasians and Africans. The greatest contributor to T1D was the HLA-DR3/DR4 genotype (OR = 16.5) in 23.9% of the patients, followed by -DR3/DR3 (OR = 8.9) in 8.7%, -DR4/DR4 (OR = 4.7) in 6.0% and -DR3/DR9 (OR = 4.9) in 2.6%. Correction by ancestry also confirmed that the DRB1*09DQB1*0202 haplotype conferred susceptibility, whereas the DRB1*07-DQB1*0202 and DRB1*11DQB1*0602 haplotypes were protective, which is similar to reports in African-American patients. By contrast, the DRB1*07-DQB1*0201 haplotype was protective in our population and in Europeans, despite conferring susceptibility to Africans. The DRB1*10-DQB1*0501 haplotype was only protective in the Brazilian population. Predisposition to T1D conferred by PTPN22 and INS-VNTR and protection against T1D conferred by the DRB1*16 allele were confirmed. Correcting for population structure is important to clarify the particular genetic variants that confer susceptibility/protection for T1D in populations with ethnic admixtures.
  • article 76 Citação(ões) na Scopus
    Positive effects of football on fitness, lipid profile, and insulin resistance in Brazilian patients with type 2 diabetes
    (2014) SOUSA, M. V. de; FUKUI, R.; KRUSTRUP, P.; PEREIRA, R. M. R.; SILVA, P. R. S.; RODRIGUES, A. C.; ANDRADE, J. L. de; HERNANDEZ, A. J.; SILVA, M. E. R. da
    We evaluated the effects of recreational football training combined with calorie-restricted diet (football+diet) vs calorie-restricted diet alone (diet) on aerobic fitness, lipid profile, and insulin resistance indicators in type 2 diabetes (T2D) patients. Forty-four T2D patients aged 48-68 years (27 females, 17 males) were randomly allocated to the football+diet group (FDG; n=22) or to the diet group (DG; n=22), of whom 19 FDG and 15 DG subjects completed the study. The football training was performed for 3x40min/week for 12 weeks. Dual-energy X-ray absorptiometry scanning, treadmill testing, and fasting blood samplings were performed pre and post-intervention. After 12 weeks, maximal oxygen uptake (VO2max) was elevated (P<0.05) by 10 +/- 4% in FDG but not in DG (-3 +/- 4%, P<0.05). After 12 weeks, reductions in blood triglycerides (0.4 +/- 0.1mmol/L), total cholesterol (0.6 +/- 0.2mmol/L), low-density lipoprotein, and very low-density lipoprotein levels were observed only in FDG. Fat mass decreased (P<0.05) by 3.4 +/- 0.4kg in FDG and 3.7 +/- 0.4kg in DG. The lower (P<0.05) glucagon and homeostatic model assessment of insulin resistance indicated an improvement in insulin sensitivity in FDG. In conclusion, football combined with restricted diet was effective in enhancing VO2max, reducing total cholesterol and triglycerides, and increasing insulin sensitivity, potentially providing better tools for the prevention of T2D complications than diet alone.
  • article 11 Citação(ões) na Scopus
    The PTPN22 1858T allele but not variants in the proximal promoter region of IL-21 gene is associated with the susceptibility to type 1 diabetes and the presence of autoantibodies in a Brazilian cohort
    (2013) MAINARDI-NOVO, D. T. O.; SANTOS, A. S.; FUKUI, R. T.; GAMBERINI, M.; CORREIA, M. R. S.; RUIZ, M. O.; MANGUEIRA, C. L. P.; MATIOLI, S. R.; VASCONCELOS, D. M.; SILVA, M. E. R.
    Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). We correlated the frequencies of islet and extra-pancreatic autoantibodies with genotypes from both loci. The case series comprised 612 T1AD patients and 792 HC. Genotyping of PTPN22 C1858T was performed on 434 T1AD patients and 689 HC. The 448 to +83 base pairs (bp) region of the IL-21 gene was sequenced in 309 Brazilian T1AD and 189 HC subjects. We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR)=1 center dot 94; P<0 center dot 001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. HLA-DR3/DR4 alleles predominated in T1AD patients. A heterozygous allelic IL-21 gene variant (g.-241 T>A) was found in only one patient. In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5-proximal region of the IL-21 gene were associated with T1AD risk. Patients with T1AD had increased frequencies of anti-islet-cell, anti-thyroid, anti-nuclear, anti-smooth muscle and anti-21-OH autoantibodies. The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies.
  • article 19 Citação(ões) na Scopus
    Carbohydrate beverages attenuate bone resorption markers in elite runners
    (2014) SOUSA, Maysa Vieira de; PEREIRA, Rosa Maria R.; FUKUI, Rosa; CAPARBO, Valeria Falco; SILVA, Maria Elizabeth Rossi da
    Objective. We evaluated the effects of carbohydrate (CHO) supplementation on markers of bone turnover in elite runners. Design. Twenty-four male runners were randomly assigned to two groups - a CHO and a control (CON) group - using a double-blind design. The participants were submitted to an overload training program (days 1-8), followed by a high-intensity intermittent running protocol (10 x 800 m) on day 9. They received a maltodextrin solution (CHO group) or a placebo solution as the CON equivalent, before, during, and after these protocols. Results. After 8 days of intensive training, baseline levels of osteocalcin (OC) decreased in both CHO and CON groups (before: 28.8 +/- 3.6 and 26.6 +/- 2.4 ng/ml, after: 24.8 +/- 3.0 and 21.9 +/- 1.6 ng/ml, respectively, p < 0.01). On day 9, at 80 min of the recovery period, carboxy-terminal of telopeptide type I collagen (CTX) serum concentration was suppressed in the CHO group (0.3 +/- 0.1 ng/ml) vs. 0.6 +/- 0.0 ng/ml for the CON group (p < 0.01). CHO supplementation was effective in decreasing CTX levels from baseline to recovery (0.5 +/- 0.1 ng/mL to 0.3 +/- 0.1 ng/mL, p < 0.001), while an increase from 0.4 +/- 0.0 ng/mL to 0.6 +/- 0.0 ng/mL (p < 0.001) was observed in the CON group. Conclusion. CHO beverage ingestion attenuated the exercise-induced increase in CTX concentration, suggesting that CHO supplementation is a potential strategy to prevent bone damage in athletes.
  • article 9 Citação(ões) na Scopus
    Th17 pathway in recent-onset autoimmune diabetes
    (2018) FORES, Jessica Pereira; CRISOSTOMO, Lindiane Gomes; ORII, Noemia Mie; SANTOS, Aritania Sousa; FUKUI, Rosa Tsuneshiro; MATIOLI, Sergio R.; VASCONCELOS, Dewton de Moraes; SILVA, Maria Elizabeth Rossi da
    Aims: Evaluate the participation of IL-17 pathway in T1D pathogenesis. T helper 17 cells are potent, highly inflammatory cells that produce interleukin 17A (IL-17A), considered a mediator of various immune disorders. However, their role in Type 1 diabetes (T1D) pathogenesis in humans is not totally elucidated. Methods: The expression of IL-17 Receptor A (IL-17RA) in peripheral T lymphocytes and IL-17A serum levels in recent-onset patients with T1D were compared with healthy controls. IL-17A gene variants were evaluated in a greater cohort. Results: Patients with recent-onset T1D (less than 6 months of diagnosis) exhibited lower expression of IL-17RA in CD3 + T (% of cells = 31.3% x 43.6%; p =.041) and CD4+ T cells (11.1% x 25.2%; p =.0019) and lower number of IL-17RA in CD4+ T cells (MFI = 1.16 x 4.56; p =.03) than controls. IL-17RA expression in CDS + T cells and IL-17A serum levels were similar in both groups. The coding regions and boundary intron sequences of IL17A were sequenced. Seventeen allelic variants, including three novel variants in exon 3 (3'UTR n) were identified, but no one was associated with T1D susceptibility, as well as the resulting haplotypes and diplotypes. The expression of IL-17RA was not correlated with metabolic variables (glucose and HbA1 c levels) or pancreatic autoantibodies titers. Conclusions: The lower expression of IL-17RA in CD3 + and CD4 + T cells suggests a reduced effect of IL-17A in immune response of recent-onset T1D patients, at least at peripheral tissues. IL-17A allelic variants were not related with T1D susceptibility.
  • article 17 Citação(ões) na Scopus
    Combination of recreational soccer and caloric restricted diet reduces markers of protein catabolism and cardiovascular risk in patients with type 2 diabetes
    (2017) SOUSA, M. Vieira De; FUKUI, R.; KRUSTRUP, P.; DAGOGO-JACK, S.; SILVA, M. E. Rossi Da
    Moderate calorie-restricted diets and exercise training prevent loss of lean mass and cardiovascular risk. Because adherence to routine exercise recommendation is generally poor, we utilized recreational soccer training as a novel therapeutic exercise intervention in type 2 diabetes (T2D) patients. We compared the effects of acute and chronic soccer training plus calorie-restricted diet on protein catabolism and cardiovascular risk markers in T2D. Fifty-one T2D patients (61.1 +/- 6.4 years, 29 females: 22 males) were randomly allocated to the soccer+diet-group (SDG) or to the dietgroup (DG). The 40-min soccer sessions were held 3 times per week for 12 weeks. Nineteen participants attended 100% of scheduled soccer sessions, and none suffered any injuries. The SDG group showed higher levels of growth hormone (GH), free fatty acids and ammonia compared with DG. After 12 weeks, insulin-like growth factor binding protein (IGFPB)-3 and glucose levels were lower in SDG, whereas insulin-like growth factor (IGF)-1/ IGFBP-3 ratio increased in both groups. After the last training session, an increase in IGF-1/IGFBP-3 and attenuation in ammonia levels were suggestive of lower muscle protein catabolism. Recreational soccer training was popular and safe, and was associated with decreased plasma glucose and IGFBP-3 levels, decreased ammoniagenesis, and increased lipolytic activity and IGF-1/IGFBP-3 ratio, all indicative of attenuated catabolism.
  • article 17 Citação(ões) na Scopus
    Lack of association between IL27 gene variants and type 1 diabetes susceptibility
    (2013) SANTOS, Aritania S.; MELO, Maria E.; CRISOSTOMO, Lindiane C.; FUKUI, Rosa T.; MATIOLI, Sergio R.; SILVA, Maria Elizabeth R.
    Background: Recently, a new subpopulation of T cells, the Th17 subset, has been implicated in autoimmune diseases. Its development is influenced by IL-27, expressed in macrophages or dendritic cells. IL-27 blockage delays the onset of diabetes in non obese diabetes mouse, but its role in type 1 diabetes (T1D) in human has not been reported yet. The aim of this study was identify variants in the entire coding regions of IL-27 gene, including the 5' proximal region, and their possible association with the disease. Methods: Those regions were amplified by polymerase chain reaction followed by automatic sequencing and restriction fragments length polymorphisms. The cohort involved 614 individuals - 318 patients with T1D (19.6 +/- 11.2 y, 129 M/189F) and 296 healthy control subjects (30.3 +/- 13.2 y, 131 M/165F). Results: We identified eight allelic variants in the 5' proximal and coding regions of IL-27 gene, including two new variants: the c.-324 C > T in the 5' proximal region and the c.521 G > C in exon 5. None of these variants compromised transcription factor binding sites or the protein structure. The frequency of the alleles and genotypes of IL-27 variants did not differ between T1D patients and controls. There was no association between IL27 variants with gender, ethnicity, age at diagnosis of diabetes or presence of pancreatic and extrapancreatic autoantibodies. Conclusion: Our findings suggest that allelic variants in IL27 are not associated with susceptibility to T1D in a Brazilian population.