Targeted massively parallel sequencing for congenital generalized lipodystrophy

ABSTRACT Objective: Our aim is to establish genetic diagnosis of congenital generalized lipodystrophy (CGL) using targeted massively parallel sequencing (MPS), also known as next-generation sequencing (NGS). Subjects and methods: Nine unrelated individuals with a clinical diagnosis of CGL were recruited. We used a customized panel to capture genes related to genetic lipodystrophies. DNA libraries were generated, sequenced using the Illumina MiSeq, and bioinformatics analysis was performed. Results: An accurate genetic diagnosis was stated for all nine patients. Four had pathogenic variants in AGPAT2 and three in BSCL2. Three large homozygous deletions in AGPAT2 were identified by copy-number variant analysis. Conclusions: Although we have found allelic variants in only 2 genes related to CGL, the panel was able to identify different variants including deletions that would have been missed by Sanger sequencing. We believe that MPS is a valuable tool for the genetic diagnosis of multi-genes related diseases, including CGL.

Association between health literacy and glycemic control in elderly patients with type 2 diabetes and modifying effect of social support / Associação entre alfabetismo em saúde e controle glicêmico em idosos com diabetes tipo 2 e efeito modificador do suporte social

ABSTRACT Objective: To investigate the association between inadequate functional health literacy, considering the Short Assessment of Health Literacy for Portuguese-speaking Adults, and glycemic control in elderly patients with type 2 diabetes, and to examine this association in low social support settings, according to Medical Outcomes Study . Methods: Cross-sectional study conducted at the diabetes referral center of a university hospital. Participants were recruited among type 2 diabetes patients aged 60 years or older, between May 2013 and November 2014. The primary outcome was the most recent glycated hemoglobin value measured within the last 6 months. Results: A total of 398 elderly patients with type 2 diabetes were evaluated. Of these, 232 were not eligible to participate. The final sample comprised 166 participants. Hierarchical multiple linear regression was performed. The following variables were entered in three blocks: sociodemographic characteristics, clinical variables and health literacy scores. Regression analysis of the interaction between health literacy and social support as a determinant of glycemic control was also performed. Mean age of subjects was 68.0 years (standard deviation of 5.9). Mean glycated hemoglobin value was 8.5% (standard deviation of 1.4). Short assessment of health literacy for Portuguese speaking adults score was independently associated with glycated hemoglobin (B=-0.059; p=0.043). The interaction between social support and health literacy score (p=0.003) was a determinant of glycemic control. Conclusion: Health literacy is associated with glycemic control. Social support may modify the relation between health literacy and glycemic control.

RESUMO Objetivo: Verificar a associação entre alfabetismo em saúde inadequado, segundo o Short Assessment of Health Literacy for Portuguese-speaking Adults , e controle glicêmico, em pacientes idosos com diabetes tipo 2, bem como avaliar tal associação no contexto de baixo suporte social, segundo o Medical Outcomes Study . Métodos: Estudo transversal conduzido no centro de referência de diabetes de um hospital universitário. Os participantes foram recrutados entre pacientes com diabetes tipo 2 com idade de 60 anos ou mais, entre maio de 2013 e novembro de 2014. O desfecho primário foi o valor mais recente de hemoglobina glicada obtido nos últimos 6 meses. Resultados: Foram avaliados 398 pacientes idosos com diabetes tipo 2. Destes, 232 não foram considerados elegíveis para participar da pesquisa. A amostra final incluiu 166 participantes. Foi realizada análise de regressão linear múltipla hierárquica com as seguintes variáveis inseridas em três blocos: características sociodemográficas, variáveis clínicas e escore de alfabetismo em saúde. Realizou-se também uma análise de regressão adicional da interação entre alfabetismo em saúde e apoio social como determinante do controle glicêmico. A média de idade dos indivíduos foi 68,0 anos (desvio-padrão de 5,9). O valor médio de hemoglobina glicada foi de 8,5% (desvio-padrão de 1,4). O Short Assessment of Health Literacy for Portuguese-speaking Adults mostrou-se independentemente associado à hemoglobina glicada (B=-0,059; p=0,043). A interação entre suporte social e escore de alfabetismo em saúde (p=0,003) foi determinante para o controle glicêmico. Conclusão: O alfabetismo em saúde está associado ao controle glicêmico. O suporte social pode modificar a relação entre o escore de alfabetismo em saúde e o controle glicêmico.