Sexual functioning, quality of life and metabolic control in patients with Diabetes Type 1 and Type 2

Objetivo: Avaliar a relação e as diferenças no funcionamento sexual, controlo metabólico, e qualidade de vida, em pacientes com diabetes Tipo 1 e Tipo 2. Método: Participaram 116 pacientes com diabetes que preencheram os instrumentos: Funcionamento Sexual Feminino, Índice Internacional de Função Eréctil, Questionário de Adesão na Diabetes e Qualidade de Vida na Diabetes. O controlo metabólico foi avaliado através do valor da hemoglobina glicosilada (HbA1c). Resultados: Na diabetes Tipo 1, o bom funcionamento sexual, nas mulheres, encontrou-se associado a melhor controlo metabólico e esta relação não se verificou nos homens. Na diabetes Tipo 2, maior impacto do tratamento associou-se a menor desejo sexual nos homens. Nas mulheres, mais preocupação com a diabetes relacionou-se com vaginismo. Os pacientes Tipo 1 percepcionaram menor qualidade de vida e mais preocupações com a doença que os pacientes Tipo 2 e apresentaram melhor funcionamento sexual que os do Tipo 2, independentemente do sexo. Conclusão: Este estudo mostra a importância do funcionamento sexual como área de intervenção na diabetes, dado a sua influência no controlo metabólico e na qualidade de vida. Assim, os programas educacionais na diabetes devem incluir a avaliação do funcionamento sexual, e os médicos devem considerá-lo quando avaliam os seus pacientes diabéticos.Introduction: To assess the relation between sexual functioning, metabolic control and quality of life in Type 1 and Type 2 diabetes patients. Method: 116 patients with diabetes participated in the study and answered the instruments: Female Sexual Functioning, International Index of Erectile Function, and Diabetes Quality of Life. Glycemic control was assessed by the value of glycosilated hemoglobin value (HbA1c). Results: For type 1 diabetes, sexual functioning, in women, was associated with better metabolic control and this relation did not occur in men. For type 2 diabetes, the greater impact of treatment was associated with low sexual desire in men. In women, more concern with diabetes was related with vaginismus. Type 1 patients showed lower quality of life and more concerns about the disease than type 2 patients and revealed better sexual functioning than type 2 patients, regardless of gender. Conclusion: This study shows the importance of sexual functioning as an important intervention area, in diabetes, given its implication on quality of life and metabolic control. Therefore, intervention programs need to include an assessment of sexual functioning and health professionals should take sexual functioning in consideration when they asses patients with diabete

Study of rare familial monogenic dyslipidemias

A dislipidemia é um distúrbio do perfil lipídico, seja por elevação ou diminuição de partículas lipídicas. O objetivo deste trabalho é fazer uma revisão dos casos com dislipidemia rara em estudo no Instituto Nacional de Saúde Doutor Ricardo Jorge, apresentando os dados clínicos e moleculares mais relevantes. O perfil lipídico foi determinado para cada caso índex e familiares e o estudo molecular dos genes envolvidos foi realizado por amplificação por PCR e sequenciação de Sanger. Foram estudados, ou está em curso o estudo, de 14 casos índex com os seguintes diagnósticos clínicos: Deficiência familiar em lipoproteína lípase (3), Lipodistrofia familiar parcial de Dunningan Tipo 2 (1), Deficiência em lípase ácida lisossomal (3), Abeta/hipobetalipoproteinemia (2), Deficiência em HDL (1), Hipertrigliceridemia autossómica recessiva (3), Sitosterolemia (1). O fenótipo clínico de cada caso índex é variável dependendo de cada condição. Foi encontrada a causa genética da doença em 8/14 doentes, estando os restantes ainda em estudo. Doentes com as várias dislipidemias raras apresentadas têm um risco acrescido de ter outras doenças graves como pancreatite, doença cardiovascular ou complicações neurológicas e devem, por esta razão, ser identificados o mais precocemente possível, de forma a minimizar ou prevenir os efeitos nefastos destas condições.Dyslipidemia is a disorder of lipid metabolism, characterized by either an increase or decrease in lipid particles. The aim of this study is to review all cases with rare dyslipidemia, studied in the National Health Institute of Portugal, presenting the most relevant clinical and molecular data. Lipid profile was determined for each index case and relatives, and molecular analysis of the genes involved was performed by PCR amplification and Sanger sequencing. This study includes 14 index cases, with the following clinical diagnoses: Familial lipoprotein lipase deficiency (3), Familial partial lipodystrophy, Dunningan Type 2 (1), Lysosomal acid lipase deficiency (3), Abeta / hypobetalipoproteinemia (2), HDL deficiency (1), Autosomal recessive hypertriglyceridemia (3), Sitosterolaemia (1). The clinical phenotype of each index case varies depending on each condition. It was possible to find the genetic cause of the disease in 8/14 patients, and the remaining are still under study. Patients with the rare dyslipidemias presented have an increased risk of having other serious disorders such as pancreatitis, cardiovascular disease or neurological complications and should, therefore, be identified as early as possible in order to minimize or prevent the adverse effects of these conditions

Avaliação de diferenças bioquímicas entre indivíduos diabéticos com e sem variantes patogénicas causadores de MODY. (PO 47)

A diabetes tipo MODY (Maturity-onset diabetes of the young) é um tipo de diabetes causada por mutações em um único gene. Existe 14 genes associados a essa doença, no entanto, a maioria dos casos de MODY é causada por alterações nos genes GCK, HNF1A, HNF1B e HNF4A. Cada subtipo desta patologia apresenta características fenotípicas, metabólicas e complicações para a saúde distintas o que exige uma adequação terapêutica diferente. Contudo a grane maioria dos casos de MODY é erroneamente diagnosticada como diabetes tipo 1 ou tipo 2, o que prejudica o diagnóstico do doente. O objetivo deste trabalho consiste na caracterização bioquímica dos participantes do Estudo Molecular de diabetes tipo MODY com base nos valores de glicémia e hemoglobina A1c inicial, indicados nos inquéritos do estudo, pelos médicos que os referenciaram, para perceber se estes valores são ou não um bom indicador de diabetes tipo MODY. Para tal foram analisados os valores de 76 participantes do estudo, com e sem mutação. Para análise estatística dos valores utilizou-se o Rstudio. Com os testes de Shapiro e Wilcox para avaliou-se e distribuição das amostras, bem como as diferenças entre os dois grupos. Os resultados desta análises não revelaram diferença estatística significativa (valor p=0.5) entre os valores de glicémia inicial dos participantes do estudo com mutação e sem mutação, nem com os valores de hemoglobina A1c (valor p= 0.19). Os resultados apresentados sustentam o argumento de que não é possível identificar corretamente pacientes com diabetes tipo MODY apenas com base nos resultados bioquímicos da glicémia e da hemoglobina A1c e que o diagnóstico genético é essencial para que o conceito de medicina personalizada seja uma realidade acessível aos pacientes diabéticos em Portugal.N/

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Torcicolo na Criança — Dois Casos

O torcicolo na criança é uma situação clínica relativamente frequente. É um sinal subestimado, por ser na maior parte das vezes devido a espasmo muscular idiopático.São consideradas as principais etiologias do torcicolo na criança.Como o torcicolo é habitualmente uma situação benigna, a sua persistência ou a associação a outros sinais ou sintomas deve determinar uma observação clínica mais cuidada.Os autores descrevem dois casos clínicos de torcicolo de etiologia relativamente pouco frequente, referentes a duas crianças que recorreram ao Serviço de Urgência do Hospital Santa Maria Maior de Barcelos. Após investigação clínica, foram diagnosticados um abcesso laterofaríngeo e um tumor cerebral da fossa posterior

Study of rare familial monogenic dyslipidemias in Portugal

Dyslipidaemia is a disorder of lipid metabolism, characterized by either an increase or decrease in lipid particles, usually associated with triglycerides (TGs), LDL cholesterol (LDL-C) or HDL cholesterol (HDL-C). Most hyperlipidemia and HDL deficiency confer an increased cardiovascular risk while hypolipidemia, such as abeta or hypobetalipoproteinemia, may present different manifestations ranging from poor weight progression to neurological manifestations. From 2009, the Cardiovascular Investigation Group has been studying rare dyslipidaemias since there were no studies about these disorders in our country. In the context of this study, several index cases and family members with clinical diagnosis of different rare monogenic dyslipidemias or other pathologies in which dyslipidemia is the clinical factor that triggers the need for a genetic diagnosis, have been referred to our lab. The aim of this study is to review all cases with rare dyslipidaemia, either already studied or ongoing in our laboratory.Work supported by centregrant (toBioISI, Centre Reference: UID/MULTI/04046/2013), from FCT/MCTES/PIDDAC, PortugalN/

Molecular study of MODY Diabetes: results update (2011-2019)

Investigadores do estudo Molecular de Diabetes tipo MODY Coordenação e equipa laboratorial – Departamento de Promoção da Saúde e Prevenção de Doenças não Transmissíveis do Instituto Nacional de Saúde Doutor Ricardo Jorge. Coordenadores: Mafalda Bourbon e Paulo Dario; Equipa laboratorial: Margarida Vaz e Gisela Gaspar; Equipa clínica: Ana Agapito (Serviço de Endocrinologia - Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central), Ana Carolina Neves (APDP – Associação Protectora dos Diabéticos de Portugal), Ana Paula Bugalho (APDP – Associação Protectora dos Diabéticos de Portugal), Bruno Almeida (APDP – Associação Protectora dos Diabéticos de Portugal), Carla Pereira (Serviço de Endocrinologia – Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Central), Carolina Moreno (Serviço de Endocrinologia, Diabetes e Metabolismo – Centro Hospitalar e Universitário de Coimbra), Fernando Fonseca (Serviço de Endocrinologia – Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central), Goreti Lobarinhas (Serviço de Pediatria – Hospital Santa Maria Maior), Henrique Vara Luiz (Serviço de Endocrinologia e Diabetes – Hospital Garcia de Orta), João Sequeira Duarte (Serviço de Endocrinologia – Hospital Egas Moniz), Maria de Lurdes Sampaio (Unidade de Endocrinologia Pediátrica, Serviço de Pediatria Médica, Departamento de Pediatria – Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Central) e Sofia Gouveia (Serviço de Endocrinologia, Diabetes e Metabolismo – Centro Hospitalar e Universitário de Coimbra).Correção: nas afiliações dos Autores e dos Investigadores do estudo Molecular de Diabetes tipo MODY (16/6/2021)A diabetes tipo MODY é uma doença monogénica que se estima que contribua para 1 a 5% de todos os casos de diabetes. Atualmente existem 14 genes associados a esta patologia cujos doentes apresentam características fenotípicas, metabólicas e genéticas muito heterogéneas. Em 2011, o Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis do Instituto Nacional de Saúde Doutor Ricardo Jorge implementou o estudo molecular da diabetes tipo MODY com o objetivo de caracterizar geneticamente estes doentes e identificar precocemente familiares em risco, de forma a contribuir para a melhor gestão do doente. O rastreio destes doentes é difícil devido a critérios clínicos pouco sensíveis e inespecíficos e por não existir um biomarcador único que nos permita fazer a diferenciação entre os vários tipos de diabetes. O estudo genético permite a correta identificação destes doentes. Entre 2011 e 2019, foram estudados 76 casos índex nos quais foram identificadas alterações patogénicas ou provavelmente patogénicas em 35,5% (27). Através do estudo em cascata dos familiares, foi possível identificar adicionalmente 17 indivíduos com MODY. Para estes doentes, o conceito de medicina personalizada é uma realidade pois, com base no diagnóstico genético, os clínicos têm a capacidade de definir uma terapêutica adequada a cada caso, bem como de estabelecer o prognóstico, aconselhamento genético e o estudo de familiares.MODY diabetes is a monogenic disease that is estimated to contribute to 1 to 5% of all diabetes cases. Currently, there are 14 genes associated with this condition whose patients present heterogeneous phenotypic, metabolic and genetic characteristics. In 2011, Department of Health Promotion and Prevention of non Communicable Diseases implemented the Molecular Study of MODY Diabetes with the aim of genetically characterizing these patients and early identify family members at risk, in order to contribute for the best management of these patients. The screening is difficult due to the low sensibility and specificity of clinical criteria, because there is no single biomarker that allows to make the differentiation between the different types of diabetes. The genetic study allows the correct identification of these patients. Between 2011 and 2019, 76 index cases were studied and in 35.5% (27) a pathogenic or probably pathogenic variant was identified. Through cascade screening of family members, it was possible to additionally identify 17 individuals with MODY. For these patients, the concept of personalized medicine is a reality because based on the genetic diagnosis, the clinicians have the ability to define an appropriate therapy for each case and establish patient prognosis, genetic counselling as well as identification of o therat risk family members.info:eu-repo/semantics/publishedVersio

Unraveling the genetic background of individuals with a clinical familial hypercholesterolemia phenotype

Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism caused by pathogenic/likely pathogenic variants in LDLR, APOB, and PCSK9 genes. Variants in FH-phenocopy genes (LDLRAP1, APOE, LIPA, ABCG5, and ABCG8), polygenic hypercholesterolemia, and hyperlipoprotein (a) [Lp(a)] can also mimic a clinical FH phenotype. We aim to present a new diagnostic tool to unravel the genetic background of clinical FH phenotype. Biochemical and genetic study was performed in 1,005 individuals with clinical diagnosis of FH, referred to the Portuguese FH Study. A next-generation sequencing panel, covering eight genes and eight SNPs to determine LDL-C polygenic risk score and LPA genetic score, was validated, and used in this study. FH was genetically confirmed in 417 index cases: 408 heterozygotes and 9 homozygotes. Cascade screening increased the identification to 1,000 FH individuals, including 11 homozygotes. FH-negative individuals (phenotype positive and genotype negative) have Lp(a) >50 mg/dl (30%), high polygenic risk score (16%), other monogenic lipid metabolism disorders (1%), and heterozygous pathogenic variants in FH-phenocopy genes (2%). Heterozygous variants of uncertain significance were identified in primary genes (12%) and phenocopy genes (7%). Overall, 42% of our cohort was genetically confirmed with FH. In the remaining individuals, other causes for high LDL-C were identified in 68%. Hyper-Lp(a) or polygenic hypercholesterolemia may be the cause of the clinical FH phenotype in almost half of FH-negative individuals. A small part has pathogenic variants in ABCG5/ABCG8 in heterozygosity that can cause hypercholesterolemia and should be further investigated. This extended next-generation sequencing panel identifies individuals with FH and FH-phenocopies, allowing to personalize each person’s treatment according to the affected pathway