RESUMO
Despite normal to high bone mineral density, patients with type 2 diabetes (T2DM) have an increased fracture risk. T2DM medications could partially account for this excess risk. The aim of this study was to assess the association between insulin use and bone fracture risk in T2DM patients. A population-based matched cohort study based on a primary care records database validated for research use (Catalonia, Spain) was performed. Propensity score (PS) for insulin use was calculated using logistic regression including predefined predictors of fractures. A total of 2,979 insulin users and 14,895 non-users were observed for a median of 1.42 and 4.58 years respectively. Major fracture rates were 11.2/1,000 person-years for insulin users, compared with 8.3/1,000 among non-users. Matched models confirmed a significant association, with an adjusted subhazard ratio (adj SHR) of 1.38 [95% CI 1.06 to 1.80] for major fractures. No differences between types of insulin or different regimens were found. Estimated number needed to harm (fracture) was 82 (95% CI 32 to 416). Insulin use appears to be associated with a 38% excess fracture risk among T2DM patients in the early stages of the disease. Fracture risk should be included among the considerations to initiate insulin treatment.
Assuntos
Bases de Dados Factuais , Diabetes Mellitus Tipo 2 , Fraturas Ósseas , Insulina , Modelos Biológicos , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/epidemiologia , Humanos , Insulina/administração & dosagem , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , EspanhaRESUMO
El complejo de Carney (CNC) es un síndrome de herencia autosómica dominante caracterizado por mixomas en diferentes localizaciones, hiperpigmentación cutánea y afectación de glándulas endocrinas. La afectación cutánea más característica es la presencia de lentiginosis y nevus azules. Los mixomas pueden hallarse en tejido subcutáneo, mamario o en región cardíaca. Los mixomas cardíacos pueden ser múltiples, localizados en cualquier cámara cardíaca y presentan mayor riesgo de recurrencia. La manifestación endocrinológica más frecuente es la presencia de un síndrome de Cushing independiente de ACTH debido a enfermedad adrenocortical nodular pigmentada primaria (primary pigmented nodular adrenal disease o PPNAD). La PPNAD puede manifestarse de manera aislada sin otras manifestaciones del CNC. Otras glándulas afectadas son la hipófisis, tiroides y gónadas. El gen PRKAR1A localizado en 17q22-24 codifica la subunidad reguladora R1A de la proteína kinasa A. Mutaciones inactivantes de este gen se encuentran en un 70% de pacientes con CNC. PRKAR1A es un componente clave de la vía celular de señalización del AMPc implicado en la presencia de tumorogénesis de origen endocrinológico. Se han descrito numerosas mutaciones en el gen PRKAR1A y la práctica totalidad de ellas conllevan cambios en la secuencia que dan lugar a codones de terminación prematuros y el RNAm resultante es degradado por la mRNA nonsense mediated decay. No existe una clara relación entre genotipo y fenotipo en los pacientes con CNC. Se ha de realizar estudio genético en todos los casos índice. El seguimiento para todas las manifestaciones clínicas del CNC deberían realizarse anualmente en los pacientes afectados. El estudio genético posibilita preparar de manera más efectiva nuevas estrategias terapéuticas y consejo genético para los pacientes y portadores, y evita la realización de pruebas innecesarias en familiares no portadores (AU)
Abstract Carney complex (CNC) is an autosomal dominantly inherited syndrome characterized by spotty skin pigmentation, cardiac and cutaneous myxoma, and endocrine over activity. Skin pigmentation includes lentigines and blue nevi. Myxomas may occur in breast, skin and heart. Cardiac myxomas may be multiple and occur in any cardiac chamber, and are more prone to recurrence. The most common endocrine gland manifestation is an ACTH-independent Cushings syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). PPNAD may occur isolated, with no other signs of CNC. Pituitary and thyroid glands and gonads are also involved. The PRKAR1A gene, located in 17 q22-24, encodes type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of patients with CNC.PRKAR1A is a key component of the c-AMP signaling pathway that has been implicated in endocrine tumorigenesis. Many different mutations have been reported in the PRKAR1A gene. In almost all cases the sequence change was predicted to lead to a premature stop codon and the resultant mutant mRNA was subject to nonsense-mediated mRNA decay. There is no cleargenotype-phenotype correlation in patients with CNC. Genetic analysis should be performed in all CNC index cases. All affected patients should be monitored for clinical signs of CNC at least once a year. Genetic diagnosis allows for more effective preparation of more appropriate and effective therapeutic strategies and genetic counseling for patients and gene carriers, and to avoid unnecessary tests to relatives not carrying the gene (AU)
Assuntos
Humanos , Complexo de Carney , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico , Mixoma/genética , Síndromes Neoplásicas Hereditárias , Neoplasias de Tecidos Moles/genéticaRESUMO
Carney complex (CNC) is an autosomal dominantly inherited syndrome characterized by spotty skin pigmentation, cardiac and cutaneous myxoma, and endocrine overactivity. Skin pigmentation includes lentigines and blue nevi. Myxomas may occur in breast, skin and heart. Cardiac myxomas may be multiple and occur in any cardiac chamber, and are more prone to recurrence. The most common endocrine gland manifestation is an ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). PPNAD may occur isolated, with no other signs of CNC. Pituitary and thyroid glands and gonads are also involved. The PRKAR1A gene, located in 17 q22-24, encodes type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of patients with CNC. PRKAR1A is a key component of the c-AMP signaling pathway that has been implicated in endocrine tumorigenesis. Many different mutations have been reported in the PRKAR1A gene. In almost all cases the sequence change was predicted to lead to a premature stop codon and the resultant mutant mRNA was subject to nonsense-mediated mRNA decay. There is no clear genotype-phenotype correlation in patients with CNC. Genetic analysis should be performed in all CNC index cases. All affected patients should be monitored for clinical signs of CNC at least once a year. Genetic diagnosis allows for more effective preparation of more appropriate and effective therapeutic strategies and genetic counseling for patients and gene carriers, and to avoid unnecessary tests to relatives not carrying the gene.