3 research outputs found
Variants of transcription factor 7-like 2 (TCF7L2) gene and incident glucose intolerance in Japanese-Brazilians
Common variants of the transcription factor 7-like 2 (TCF7L2) gene have been found to be associated with type 2 diabetes in different ethnic groups. The Japanese-Brazilian population has one of the highest prevalence rates of diabetes. Therefore, the aim of the present study was to assess whether two single-nucleotide polymorphisms (SNPs) of TCF7L2, rs7903146 and rs12255372, could predict the development of glucose intolerance in Japanese-Brazilians. In a population-based 7-year prospective study, we genotyped 222 individuals (72 males and 150 females, aged 56.2 ± 10.5 years) with normal glucose tolerance at baseline. In the study population, we found that the minor allele frequency was 0.05 for SNP rs7903146 and 0.03 for SNP rs12255372. No significant allele or genotype association with glucose intolerance incidence was found for either SNP. Haplotypes were constructed with these two SNPs and three haplotypes were defined: CG (frequency: 0.94), TT (frequency = 0.027) and TG (frequency = 0.026). None of the haplotypes provided evidence for association with the incidence of glucose intolerance. Despite no associations between incidence of glucose intolerance and SNPs of the TCF7L2 gene in Japanese-Brazilians, we found that carriers of the CT genotype for rs7903146 had significantly lower insulin levels 2 h after a 75-g glucose load than carriers of the CC genotype. In conclusion, in Japanese-Brazilians, a population with a high prevalence of type 2 diabetes, common TCF7L2 variants did not make major contributions to the incidence of glucose tolerance abnormalities.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de EndocrinologiaUniversidade de São Paulo Instituto do CoraçãoUNIFESP, EPM, Disciplina de EndocrinologiaSciEL
Estratificação do risco de doença cardiovascular no diabetes mellitus monogênico tipo MODY
To identify among asymptomatic individuals the sub-group that has higher risk to develop cardiovascular events is paramount to strategies towards the reduction of cardiovascular event rates. Some studies demonstrated that asymptomatic diabetic patients with elevated calcium score (CAC) have higher incidence of induced myocardial ischemia and worse prognosis. In addition, CAC has demonstrated superiority when compared to traditional risk markers as predictors of myocardial ischemia and cardiac events in this population. MODY is defined as familial diabetes with early onset, autosomal dominant transmission and associated to defects in insulin secretion. Cardiovascular disease (CVD) in patients with monogenic diabetes is not well studied and very few publications focus on the analysis of risk factors, classic and non-classic markers of CVD in less common types of diabetes as MODY. Objective: To describe the prevalence of risk factors for CVD in patients with GCK-MODY. Patients and Methods: Three groups of patients were investigated: one with 29 patients with GCK-MODY (aged 30 to 46 years), a control group (C) with 26 relatives or spouses, non-carriers of GCK gene mutations and without hyperglycemia (aged 34 to 47 years), and a third group with 24 patients with type 2 diabetes (DM2) followed in the Diabetes Center at UNIFESP (aged 50 to 59 years). Laboratory investigation included glycated hemoglobin (A1c) fasting plasma glucose, high-sensitivity C-reactive protein (hsCRP), total cholesterol and fractions, and serum insulin. Calcium score (CAC) was used in the evaluation of the atherosclerosis in these patients (Agatston score). Results: Female gender was more frequent in the GCK-MODY (79.3%) and DM2 group (62.5%) than C group (38.5%). Patients were younger in the GCK-MODY and C groups in relation to the DM2 group (Median.age of 41; 42 and 56.5 years, respectively). BMI was lower in the GCK-MODY and C groups in relation to the DM2 group (Median of 23.7; 25.5 and 28.8 kg/m2, respectively) The prevalence of hypertension was 3.4% in the GCK-MODY group, 15.4% in the C group and 91.7% in the DM2 group (GCK vs. C, p-=0.51; DM2 vs. C, p=2x10-7 and DM2 vs. GCK, p=4x10-11). CAC score ≥10 was seen in 54.2% in the DM2 group, in 7.7% of the C group and in 6.9% of the GCK group (DM2 vs. C, p=0.001; DM2 vs.GCK, p=0.0006), no differences were seen between GCK and C groups. Framingham risk scores in 10 years was 13% in the DM2 group, 4% in C group and 3% in the GCK group (DM2 vs,.C, p= 4 X 10-5; DM2 vs. GCK, p=4 X 10 -6), no differences were seen between GCK and C groups. Median. hsCRP was higher in DM2 group in relation to the GCK group (3.15 vs. 1.42 mg/dL, p=0.03) and C group (3.15 vs. 1.70mg/dL, p=0.06). Albumin excretion rate above 30 mg/24 hours, diabetic retinopathy, and diabetic neuropathy were seen exclusively in the DM2 group. Conclusion: Patients with GCK-MODY have a better cardiovascular risk profile when compared to DM2 patients. These individuals have low risk for cardiovascular disease in spite of having hyperglycemia throughout their lives. Probably this could be related to the low magnitude of the hyperglycemia and the low frequency of other classic risk factors.Identificar entre os indivíduos assintomáticos o subgrupo que poderá apresentar maior risco de desenvolver eventos cardiovasculares é fundamental em qualquer estratégia voltada para a diminuição de taxas de eventos cardiovasculares. Alguns estudos mostram que diabéticos assintomáticos com escore de cálcio (ECC) elevado têm maior incidência de isquemia miocárdica induzida e pior prognóstico. Além disso, o ECC mostra superioridade em relação aos marcadores de risco tradicionais como preditor de isquemia miocárdica e eventos cardiovasculares nessa população. O diabetes monogênico tipo MODY (Maturity Onset Diabetes of the Young) é definido como diabetes familiar com idade de diagnóstico precoce, modo de transmissão autossômico-dominante e associado a defeitos na secreção de insulina. A doença cardiovascular (DCV) em pacientes com diabetes monogênico é um tema raramente estudado e são poucos os estudos que abordaram a análise de fatores de risco, marcadores clássicos e não clássicos de DCV em tipos raros de diabetes, como o MODY. Objetivo: Descrever a prevalência de fatores de risco para a DCV em pacientes com GCK-MODY. Casuística e Métodos: Foram estudados três grupos: um com 29 pacientes GCK- MODY (idade entre 30-46 anos), um grupo controle (C) com 26 familiares ou cônjuges não-portadores de mutações no gene GCK e sem hiperglicemia (faixa etária entre 34-47 anos) e um grupo com 24 pacientes com diabetes mellitus tipo 2 (DM2) acompanhados no Centro de Diabetes da UNIFESP (faixa etária entre 50- 59 anos). A investigação laboratorial incluiu as dosagens de: hemoglobina glicada (A1c), albuminúria, glicemia de jejum, proteína C reativa ultrassensível (PCR-US), colesterol total e frações e insulina. Foi realizado o ECC na avaliação da aterosclerose destes pacientes (escore de Agatston). Resultados: Observou-se maior frequência do sexo feminino nos grupos GCK (79,3%) e DM2 (62,5%) do que no C (38,5%), pacientes mais jovens nos grupos GCK e C em relação ao DM2 (mediana de 41; 42 e 56,5 anos, respectivamente), menor IMC nos grupos GCK e C em relação ao DM2 (mediana 23,7; 25,5 e 28,8 kg/m2, respectivamente). A prevalência de hipertensão arterial foi de 3,4% no grupo GCK, 15,4% no C e 91,7% no DM2 (GCK vs. C, p=0,51; DM2 vs. C, p=2x10-7 e DM2 vs. GCK, p=4x10-11). ECC ≥10 foi observado em 54,2% do grupo DM2, 7,7% do grupo C e 6,9% do grupo GCK (DM2 vs. C, p=0,001; DM2 vs. GCK, p=0,0006), não foram observadas diferenças significantes entre os grupos GCK e C. O escore do risco de Framingham em 10 anos foi 13% no grupo DM2, 4% no grupo C e 3% no grupo GCK (DM2 vs. C, p=4 X 10-5; DM2 vs. GCK, p=4 X 10 -6); não foram observadas diferenças entre os grupos GCK e C. A mediana do PCR-US foi maior no grupo DM2 em relação ao grupo GCK-MODY (3,15 vs.1.42 mg/L, p=0,03) e C (3,15 vs.1,70; p=0,06). Taxa de excreção de albumina acima de 30 mg/24 horas, retinopatia diabética e neuropatia diabética foram observadas exclusivamente no grupo de DM 2. Conclusão: Pacientes com GCK-MODY possuem um melhor perfil de fator de risco cardiovascular quando comparado com o DM2. Estes indivíduos carregam baixo risco para o DCV, apesar de ter hiperglicemia ao longo da vida. Este achado, provavelmente está relacionado à pequena magnitude da hiperglicemia e à baixa frequência de outros fatores de risco clássicos.Dados abertos - Sucupira - Teses e dissertações (2021
Congress of Chemical Biology and Symposium of Biological Sciences Department
Essa publicação é a compilação dos resumos científicos apresentados no "III Congresso do Programa de Pós-Graduação em Biologia Química e IV Simpósio do Departamento de Ciências Biológicas"Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES