Doença hepática gordurosa não alcoólica (DHGNA) em pacientes morbidamente obesos submetidos à cirurgia bariátrica : correlação entre os achados histopatológicos das biópsias hepáticas intraoperatórias e estado glicêmico basal

Introdução: A Doença Hepática Gordurosa Não Alcoólica (DHGNA) tem como causa principal a obesidade. Atualmente não existe tratamento medicamentoso específico para DHGNA. A cirurgia bariátrica surge como uma alternativa de tratamento em pacientes morbidamente obesos. Objetivos: Analisar, através de biópsia hepática intra-operatória, o grau de comprometimento hepático em obesos submetidos à cirurgia bariátrica, correlacionando os achados histopatológicos com o estado glicêmico dos pacientes. Métodos: Estudo de coorte prospectivo incluindo 521 pacientes submetidos à cirurgia bariátrica de julho de 2001 até dezembro de 2016. Os pacientes foram classificados em três grupos de acordo com o status glicêmico basal: 167(32,05%) diabéticos tipo 2 (G1), 132 (25,33%) pré-diabéticos (G2) e 222 (42,61%) obesos normoglicêmicos (G3). Foram obtidas biópsias hepáticas transoperatórias, as quais foram classificadas conforme os critérios de Brunt e do NASH-CRN. As variáveis clínicas e bioquímicas e histológicas foram comparadas antes da cirurgia e durante o seguimento pós-operatório. Resultados: A prevalência de DHGNA nesta coorte foi de 95%. Não houve diferença quanto ao gênero e IMC entre os grupos. Observaram-se taxas mais altas de fibrose (56,4% G1 vs 29,2% G2 vs 28,6% G3 p<0,001) e Esteatohepatite Não Alcoólica (EHNA) (59,4% G1vs 49,2% G2 vs 36% G3 p <0,001) nos pacientes diabéticos. Apenas 1,5 %, dos diabéticos apresentaram histologia normal (vs 7,76% G2 vs 15,7% G3).Introduction: Obesity is the main cause of nonalcoholic fatty liver disease (NAFLD), for which there is currently no specific medical treatment. Bariatric surgery is a treatment alternative for morbidly obese patients. Objectives: Use an intraoperative liver biopsy to analyze the degree of liver damage in obese patients submitted to bariatric surgery and correlates the histopathological findings with glucose status. Methods: Prospective cohort study of 521 morbid obese patients undergoing bariatric surgery from July 2001 to December 2016, classified into three groups according to their baseline glucose status: 167 (32.05%) type 2 diabetes (G1), 132 (25.33%) pre-diabetic (G2) and 222 (42.61%) normoglycemic obese (G3). Patients using potentially hepatotoxic medications and a history of ethanol consumption or viral hepatitis were excluded. Intraoperative liver biopsies were obtained and classified in accordance with Brunt and NASH-CRN criteria. Clinical, biochemical and histopathological variables were compared before surgery and during postoperative follow-up. Results: The prevalence NAFLD was 95%. There was no intergroup difference for sex and BMI. Higher rates of fibrosis (56.4% G1 vs. 29.2% G2 vs. 28.6% G3 p<0.001) and nonalcoholic steatohepatitis (NASH) (59.4% G1vs 49.2% G2 vs. 36% G3 p <0.001) were observed in the diabetic patients. Only 1.5 % of diabetics showed normal histology (vs. 7.76% G2 and 15.7% G3)

Doença hepática gordurosa não alcoólica (DHGNA) em pacientes morbidamente obesos submetidos à cirurgia bariátrica : correlação entre os achados histopatológicos das biópsias hepáticas intraoperatórias e estado glicêmico basal

Introdução: A Doença Hepática Gordurosa Não Alcoólica (DHGNA) tem como causa principal a obesidade. Atualmente não existe tratamento medicamentoso específico para DHGNA. A cirurgia bariátrica surge como uma alternativa de tratamento em pacientes morbidamente obesos. Objetivos: Analisar, através de biópsia hepática intra-operatória, o grau de comprometimento hepático em obesos submetidos à cirurgia bariátrica, correlacionando os achados histopatológicos com o estado glicêmico dos pacientes. Métodos: Estudo de coorte prospectivo incluindo 521 pacientes submetidos à cirurgia bariátrica de julho de 2001 até dezembro de 2016. Os pacientes foram classificados em três grupos de acordo com o status glicêmico basal: 167(32,05%) diabéticos tipo 2 (G1), 132 (25,33%) pré-diabéticos (G2) e 222 (42,61%) obesos normoglicêmicos (G3). Foram obtidas biópsias hepáticas transoperatórias, as quais foram classificadas conforme os critérios de Brunt e do NASH-CRN. As variáveis clínicas e bioquímicas e histológicas foram comparadas antes da cirurgia e durante o seguimento pós-operatório. Resultados: A prevalência de DHGNA nesta coorte foi de 95%. Não houve diferença quanto ao gênero e IMC entre os grupos. Observaram-se taxas mais altas de fibrose (56,4% G1 vs 29,2% G2 vs 28,6% G3 p<0,001) e Esteatohepatite Não Alcoólica (EHNA) (59,4% G1vs 49,2% G2 vs 36% G3 p <0,001) nos pacientes diabéticos. Apenas 1,5 %, dos diabéticos apresentaram histologia normal (vs 7,76% G2 vs 15,7% G3).Introduction: Obesity is the main cause of nonalcoholic fatty liver disease (NAFLD), for which there is currently no specific medical treatment. Bariatric surgery is a treatment alternative for morbidly obese patients. Objectives: Use an intraoperative liver biopsy to analyze the degree of liver damage in obese patients submitted to bariatric surgery and correlates the histopathological findings with glucose status. Methods: Prospective cohort study of 521 morbid obese patients undergoing bariatric surgery from July 2001 to December 2016, classified into three groups according to their baseline glucose status: 167 (32.05%) type 2 diabetes (G1), 132 (25.33%) pre-diabetic (G2) and 222 (42.61%) normoglycemic obese (G3). Patients using potentially hepatotoxic medications and a history of ethanol consumption or viral hepatitis were excluded. Intraoperative liver biopsies were obtained and classified in accordance with Brunt and NASH-CRN criteria. Clinical, biochemical and histopathological variables were compared before surgery and during postoperative follow-up. Results: The prevalence NAFLD was 95%. There was no intergroup difference for sex and BMI. Higher rates of fibrosis (56.4% G1 vs. 29.2% G2 vs. 28.6% G3 p<0.001) and nonalcoholic steatohepatitis (NASH) (59.4% G1vs 49.2% G2 vs. 36% G3 p <0.001) were observed in the diabetic patients. Only 1.5 % of diabetics showed normal histology (vs. 7.76% G2 and 15.7% G3)

The Catalase –262C/T Promoter Polymorphism and Diabetic Complications in Caucasians with Type 2 Diabetes

Catalase is a central antioxidant enzyme constituting the primary defense against oxidative stress. In this study, we investigated whether the functional –262C/T polymorphism in the promoter of catalase gene is associated with the presence of diabetic retinopathy (DR), diabetic nephropathy (DN) and ischemic heart disease (IHD) in 520 Caucasian-Brazilians with type 2 diabetes. The –262C/T polymorphism was also examined in 100 Caucasian blood donors. Patients underwent a clinical and laboratory evaluation consisting of a questionnaire, physical examination, assessment of diabetic complications and laboratory tests. Genotype analysis was performed using the polymerase chain reaction followed by digestion with restriction enzyme. The genotype and allele frequencies of the –262C/T polymorphism in patients with type 2 diabetes were very similar to those of blood donors (T allele frequency = 0.20 and 0.18, respectively). Likewise, there were no differences in either genotype or allele frequencies between type 2 diabetic patients with or without DR, DN or IHD. Thus, our results do not support the hypothesis that the –262C/T polymorphism is related to the development of DR, DN or IHD in patients with type 2 diabetes. Further studies are necessary to elucidate the role of catalase gene polymorphisms in the pathogenesis of diabetic complications

História familiar de diabetes tipo 2 em pacientes do sul do Brasil e sua influência nas características dessa doença

Objetivos: Investigar a presença de história materna e paterna de diabetes mellitus tipo 2 (DM) entre familiares de 644 pacientes diabéticos tipo 2 provenientes do sul do Brasil, bem como avaliar sua influência nas características clínicas dessa doença. Materiais e Métodos: A história familiar de DM tipo 2 foi investigada através de um questionário, sendo que a presença de história materna e paterna foi investigada em duas gerações. Dados completos sobre história familiar foram obtidos para 396 pacientes. Resultados: Em geral, 76,6% dos pacientes reportaram ao menos um familiar em primeiro grau afetado por DM tipo 2. Além disso, 31,6% dos pacientes relataram uma história materna de DM tipo 2 e 12,6% relataram uma história paterna. Pacientes com história materna e/ou paterna apresentaram uma idade de diagnóstico de DM tipo 2 mais baixa quando comparado a pacientes sem história familiar. Adicionalmente, pacientes que relataram apenas história paterna de DM tipo 2 apresentaram uma maior freqüência de hipertensão do que pacientes sem história familiar. Conclusões: Nosso estudo sugere que há um efeito materno significativo na transmissão do DM tipo 2 no Sul do Brasil, e que a maioria das características clínicas dessa doença não difere entre pacientes com e sem história familiar de DM tipo 2.Objective: To investigate the presence of maternal and paternal history of type 2 diabetes mellitus (DM) in relatives of 644 type 2 diabetic patients from Southern Brazil, and also to evaluate its influence on the clinical characteristics of this disease. Patients and Methods: Familial history of type 2 DM was investigated by a questionnaire. The maternal and paternal history was investigated over two generations. Complete data sets on familial history were obtained from 396 patients. Results: In general, 76.6% of the patients reported at least one first-degree affected relative. Besides, 31.6% of the patients reported a maternal history of type 2 DM and 12.6% reported a paternal history. Patients with maternal and/or paternal history presented a lower age at type 2 DM diagnosis when compared to patients without familial history. In addition, patients with only paternal history presented a higher frequency of hypertension than patients with no familial history. Conclusions: This study suggests that there is a significant maternal effect in the transmission of type 2 DM in Southern Brazil, and that most of the clinical characteristics of this disease do not differ between patients with or without familial history of type 2 DM

The european-specific mitochondrial cluster J/T could confer an increased risk of insulin-resistance and type 2 diabetes : an analysis of the m.4216T > C and m.4917A > G variants

The aims of this studywere to investigate the contributions of the mitochondrialDNAm.4216T>Cand m.4917A> Gvariants, and also of the European-specific mitochondrial cluster J/T, to the development of type 2 diabetes mellitus in Caucasian-Brazilian patients from Southern Brazil. We analyzed 347 type 2 diabetes patients and 350 control subjects. Variant frequencies in patients and control subjects were compared using χ2 tests or odds ratio. We also compared clinical and laboratory characteristics among patients with and without the variants. We found that the frequencies of the m.4216T > C and m.4917A > G variants are higher in diabetic patients than in control subjects. Moreover, haplogroups J (partially defined by the presence of the m.4216T > C variant only) and T (partially defined by the presence of both m.4216T > C and m.4917A > G variants) are more frequent in the type 2 diabetic group than in the control group. Patients belonging to the cluster J/T are more insulin resistant than patients of other haplogroups. In conclusion, our results indicate the association of the cluster J/T (as suggested by analyses of the m.4216T > C and m.4917A > G variants) with insulin resistance and type 2 diabetes

The european-specific mitochondrial cluster J/T could confer an increased risk of insulin-resistance and type 2 diabetes : an analysis of the m.4216T > C and m.4917A > G variants

The aims of this studywere to investigate the contributions of the mitochondrialDNAm.4216T>Cand m.4917A> Gvariants, and also of the European-specific mitochondrial cluster J/T, to the development of type 2 diabetes mellitus in Caucasian-Brazilian patients from Southern Brazil. We analyzed 347 type 2 diabetes patients and 350 control subjects. Variant frequencies in patients and control subjects were compared using χ2 tests or odds ratio. We also compared clinical and laboratory characteristics among patients with and without the variants. We found that the frequencies of the m.4216T > C and m.4917A > G variants are higher in diabetic patients than in control subjects. Moreover, haplogroups J (partially defined by the presence of the m.4216T > C variant only) and T (partially defined by the presence of both m.4216T > C and m.4917A > G variants) are more frequent in the type 2 diabetic group than in the control group. Patients belonging to the cluster J/T are more insulin resistant than patients of other haplogroups. In conclusion, our results indicate the association of the cluster J/T (as suggested by analyses of the m.4216T > C and m.4917A > G variants) with insulin resistance and type 2 diabetes

The G1888A variant in the mitochondrial 16S rRNA gene may be associated with Type 2 diabetes in Caucasian-Brazilian patients from southern Brazil

Aim: To compare the frequencies of the G1888A variant in the mitochondrial 16S rRNA gene between patients with Type 2 diabetes and non-diabetic control subjects from southern Brazil. Methods: We analysed 520 Type 2 diabetic patients (389 Caucasian- and 131 African-Brazilians) and 530 control subjects (400 Caucasian- and 130 African-Brazilians). DNA samples were amplified by polymerase chain reaction and digested with the RsaI enzyme. Variant frequency in patients and control subjects was compared using χ2 test, Fisher's exact test or odds ratio test. We also investigated the frequency of the G1888A variant in a subgroup of the patients with a maternal history of Type 2 diabetes plus two or more features of maternally inherited diabetes and deafness. Results: The 1888A allele does not seem to be associated with Type 2 diabetes in African-Brazilians (frequency of 3.8% in patients and 0.8% in control subjects; PFisher = 0.213). However, in Caucasian-Brazilians, the 1888A allele was significantly associated with diabetes (12.3% in patients vs. 3.5% in control subjects; OR = 3.881; 95% CI 2.106-7.164; P < 0.001) and also with higher levels of insulin resistance. The majority of the patients carrying the 1888A allele did not have clinical features of maternally inherited diabetes and deafness. Conclusion: The present study indicates the association of the mitochondrial G1888A variant with Type 2 diabetes and insulin resistance in Caucasian-Brazilian patients from southern Brazil. However, further studies are required to confirm its effects on mitochondrial function and the role of these effects on the pathogenesis of Type 2 diabetes