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Not Every Diabetic Child Has Type 1 Diabetes Mellitus Nem Toda Criança Diabética É Tipo 1 Thais Della Manna*

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Not Every Diabetic Child Has Type 1 Diabetes Mellitus Nem Toda Criança Diabética É Tipo 1 Thais Della Manna* 0021-7557/07/83-05-Supl/S178 Jornal de Pediatria Copyright © 2007 by Sociedade Brasileira de Pediatria ARTIGO DE REVISÃO Not every diabetic child has type 1 diabetes mellitus Nem toda criança diabética é tipo 1 Thais Della Manna* Resumo Abstract Objetivo: Apesar de o diabetes melito tipo 1 de origem Objective: Although it is type 1 diabetes mellitus of autoimmune autoimune ser o mais prevalente na infância e adolescência, outras origin that is most prevalent in childhood and adolescence, other formas de diabetes também podem acometer essa população, forms of diabetes can also affect this population, resulting in different implicando em prognóstico e tratamentos diferentes. prognosis and treatment. Fontes dos dados: Foram utilizadas informações através de Sources: Information was obtained by means of a bibliographic revisão bibliográfica realizada por busca direta de artigos científicos review, carried out by running searches for scientific articles in the nas bases de dados MEDLINE e LILACS, além de publicações clássicas MEDLINE and LILACS databases, in addition to classic publications referentes ao tema, sendo escolhidas as mais representativas. on the subject, with the most representative being chosen. Síntese dos dados: Este artigo discute os mecanismos Summary of the findings: This article discusses the fisiopatológicos, quadro clínico e tratamento das diversas formas de pathophysiological mechanisms, clinical presentation and treatment diabetes que acometem a faixa etária pediátrica, como diabetes of the various forms of diabetes that affect the pediatric age group, melito tipo 1, diabetes melito tipo 2, diabetes do tipo maturity-onset such as type 1 diabetes mellitus, type 2 diabetes mellitus, diabetes of youth, diabetes neonatal, diabetes mitocondrial, diabetes maturity-onset diabetes of youth, neonatal diabetes, mitochondrial da lipodistrofia generalizada, diabetes secundário a outras diabetes, diabetes of generalized lipodystrophy, diabetes secondary pancreatopatias, diabetes secundário a outras endocrinopatias, to other pancreatic diseases, diabetes secondary to other endocrine diabetes associado a infecções e drogas citotóxicas e diabetes diseases, diabetes associated with infections and cytotoxic drugs relacionado a algumas síndromes genéticas. and diabetes related to certain genetic syndromes. Conclusão: O reconhecimento do mecanismo fisiopatológico Conclusions: Recognition of the primary pathophysiologic primário da forma de diabetes apresentada pode orientar seu mechanism of the form of diabetes presented can guide specific tratamento específico, otimizando seu controle metabólico e treatment, optimizing metabolic control and minimizing minimizando suas complicações a longo prazo. complications over the long term. J Pediatr (Rio J). 2007;83(5 Supl):S178-183: Diabetes melito, J Pediatr (Rio J). 2007;83(5 Suppl):S178-183: Diabetes mellitus, diagnóstico diferencial, criança, diabetes melito neonatal, síndromes. differential diagnosis, child, diabetes mellitus neonatal, syndromes. Introdução beta das ilhotas de Langerhans, resultando na incapacidade O diabetes melito (DM) é uma doença metabólica de eti- progressiva de produzir insulina. Esta agressão é geralmente ologia múltipla. É caracterizado pela hiperglicemia crônica de natureza auto-imune, resultante tanto de processos gené- resultante de distúrbios no metabolismo de carboidratos, pro- ticos quanto ambientais. Existe grande propensão à cetoaci- teínas e gorduras, em função de secreção insuficiente e/ou dose diabética, que é um quadro grave de descompensação ausente de insulina, como também por defeitos da sua ação diabética com risco de vida iminente. A insulina é sempre nos tecidos-alvo da insulina (fígado, tecidos muscular e adi- necessária no tratamento do DM tipo 1, devendo ser institu- poso)1. ída assim que o diagnóstico estiver estabelecido. A classificação atual do DM baseia-se em conhecimentos fisiopatológicos, incluindo quatro classes clínicas: DM tipo1, Os marcadores sorológicos da destruição imunológica das DM tipo 2, outros tipos específicos de DM e DM gestacional. células beta-pancreáticas são os auto-anticorpos para as célu- las das ilhotas (ICA), para a insulina (IAA), para a descarbo- Diabetes melito do tipo 1 xilase do ácido glutâmico (GAD 65) e para a tirosina fosfatase ODMtipo1éaforma mais freqüente entre crianças e ado- (IA 2). Freqüentemente, mais de um desses anticorpos estão lescentes, causada por destruição parcial ou total das células presentes em 90% dos indivíduos à época do diagnóstico2. * Doutora em Ciências, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP. Médica assistente, Unidade de Endocrinologia Pediátrica, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP. Como citar este artigo: Della Manna T. Not every diabetic child has type 1 diabetes mellitus. J Pediatr (Rio J). 2007;83(5 Suppl):S178-183. doi 10.2223/JPED.1714 S178 Diabetes melito em crianças - Della Manna T Jornal de Pediatria - Vol. 83, Nº 5(Supl), 2007 S179 Diabetes melito do tipo 2 que é uma forma de diabetes herdada geneticamente, de iní- cio precoce, causada por defeitos de funcionamento da célula O DM tipo 2 resulta de mecanismos de resistência à ação beta, apresentando padrão de transmissão autossômica da insulina associados a defeitos de secreção deste hormô- dominante. No DM tipo 1, os pais geralmente não são nio, correspondendo à forma mais prevalente de diabetes no diabéticos; no MODY, um dos pais costuma estar afetado; e mundo. Pode acontecer em qualquer idade, mas é mais fre- no DM tipo 2, os dois pais são diabéticos do tipo 2 ou intole- qüentemente diagnosticado após os 40 anos de idade. O rantes à glicose6. aumento do número de casos de DM tipo 2 no jovem acom- panhou o aumento da prevalência de obesidade na infância. No DM tipo MODY, um nível discreto de hiperglicemia cos- Atualmente, o DM tipo 2 representa uma proporção conside- tuma passar despercebido, sendo revelado somente durante rável de casos de diabetes recém-diagnosticados na popula- doenças intercorrentes ou durante a gravidez. Deve-se sus- ção pediátrica de algumas clínicas da América do Norte, peitar de MODY diante de um paciente que apresente diabe- principalmente adolescentes de minorias populacionais, como tes não dependente de insulina, de início precoce, com hispano-americanos, afro-americanos e índios norte- antecedente de diabetes em pelo menos um membro da famí- americanos e canadenses, assim como em algumas ilhas do lia com idade inferior a 25 anos, como também pela presença oceano Pacífico. As mudanças de estilo de vida ocorridas no de três gerações sucessivas afetadas pela doença. último século, como alterações na dieta e dramática redução Pelo menos cinco genes já foram relacionados aos subti- da atividade física, assim como a exposição fetal à hiperglice- pos de MODY: mia, na forma de diabetes gestacional e intolerância à glicose α na gestação, foram determinantes de impacto neste fenôme- - Gene do Fator Nuclear do Hepatócito - 4 (MODY 1) no3. - Gene da Glucoquinase - (MODY 2) - Gene do Fator Nuclear do Hepatócito - 1α (MODY 3) Não existem marcadores específicos para o DM tipo 2. Baixo peso ao nascimento e obesidade na fase pré-puberal - Gene do Fator Promotor da Insulina (IPF-1) (MODY 4) são fatores de risco para resistência insulínica e diabetes3,4. - Gene do Fator Nuclear do Hepatócito - 1β (MODY 5) O DM tipo 2 costuma acometer jovens na fase intermedi- As mutações no gene da glucoquinase (MODY 2) e em ária da puberdade com idade média de 13,5 anos, afetando fatores de transcrição nucleares (MODY 1, 3,4e5)provocam mais meninas que meninos, na proporção de 1,6:1 a 3:1. A disfunção da célula beta com diversos graus de insuficiência obesidade está presente na grande maioria dos pacientes que insulínica. Ambos os sexos são afetados, não havendo asso- freqüentemente apresentam índice de massa corpórea (IMC) ciação com obesidade. As principais características clínicas e superior ao percentil 85 para sexo e idade. A acantose nigri- genéticas dos vários subgrupos de MODY são apresentadas cans, uma lesão cutânea hiperpigmentada e aveludada que na Tabela 1. O diagnóstico diferencial de MODY com DM tipo 1 acomete principalmente superfícies de flexura como pescoço e 2 está ilustrado na Tabela 2. e axilas, está presente em 60 a 95% dos casos. O antece- Outras formas de diabetes melito na infância e dente familiar para DM tipo 2 é muito importante, existindo adolescência geralmente muitos membros da família afetados em várias gerações5. Crianças com DM tipo 2 costumam apresentar Outras condições patológicas podem cursar com DM na graus de hiperglicemia mais leves, níveis mais elevados de infância. insulina e peptídeo C, graus mais baixos de cetonúria e de aci- O DM neonatal é bastante raro, acontecendo com freqüên- dose metabólica. A relação resistência à insulina/ hiperinsu- cia de 1/400.000 a 1/600.000 nascidos vivos. Manifesta-se linemia está presente desde uma idade precoce nas como um quadro de hiperglicemia, episódios de desidratação populações de alto risco, indicando susceptibilidade ao DM em um recém-nascido com dificuldade de ganho de peso e, tipo 2. freqüentemente, com antecedente de retardo de cresci- Evidências recentes mostram que o DM tipo 2 não apre- mento intra-uterino. A cetoacidose é mais rara, mas poderá senta prognóstico favorável, acarretando um enorme impacto acontecer se a insulinoterapia não for iniciada. físico, psicológico, econômico e social. Crianças diabéticas do
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