RESUMO
PURPOSE OF REVIEW: The aim was to review evidence about diabetes secondary to hereditary pancreatitis, seeking novel diagnostic and treatment features. RECENT FINDINGS: Hereditary pancreatitis (HP) is an autosomal dominant condition, characterized by recurrent episodes of acute pancreatitis, progression to fibrosis, and chronic pancreatitis. Clinical presentation includes diabetes of the exocrine pancreas (DEP). HP prevalence ranges from 0.3 to 0.57 per 100,000 people, with up to 80% of these develop DEP. This condition often requires specific interventions: with regard to metabolic control, metformin is the first choice for those with mild DEP, and for those in advanced disease, insulin is considered the first-line therapy. Insulin analogues and insulin pump therapy are preferred due to the brittle glycemic pattern and risk of hypoglycemia. In case of exocrine insufficiency, pancreatic enzyme replacement therapy is recommended. Pancreatic polypeptide administration is a promising novel treatment feature. DEP due to HP appears to be a misdiagnosed condition. The requirement of specific management demonstrates the importance of this matter; therefore, appropriate recognition and classification are important.
Assuntos
Diabetes Mellitus/genética , Pâncreas Exócrino/patologia , Pancreatite Crônica/genética , Tripsina/genética , Doença Aguda , Carcinoma Ductal Pancreático/etiologia , Quimotripsina/genética , Complicações do Diabetes/complicações , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/terapia , Insuficiência Pancreática Exócrina/genética , Insuficiência Pancreática Exócrina/fisiopatologia , Insuficiência Pancreática Exócrina/terapia , Fibrose/etiologia , Humanos , Pâncreas Exócrino/fisiopatologia , Neoplasias Pancreáticas/etiologia , Pancreatite Crônica/complicações , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/fisiopatologia , Recidiva , Fatores de Risco , Inibidor da Tripsina Pancreática de Kazal/genéticaRESUMO
The prevalence and high levels of anti-insulin antibodies (IA) have frequently been associated with brittle diabetes, lipodystrophy in the areas where the insulin is injected and/or poor metabolic control. When this happens the usual criterion adopted is the empirical change of insulin type and/or formulation intending to diminish the IA level and then to decrease the undesirable side-effects. Here, we present a rational two step radiometric method consisting in: A) a first-line radioligand binding assay (RBA) to assess IA in sera of these patients and detecting those with high levels. B) applying a displacement assay (RIA) to determine the in vitro cross-reactivity parameters (affinity constants and selectivity ratios) that quantify the relative degree of interaction between antibodies and alternative insulin analogs. From these results we conclude that conventional criteria for selection of insulin analogs, in terms of pharmacokinetic and pharmacodinamic parameters, should be complemented with an appropriate test to assess affinity parameters when high IA title is demonstrated. â¢This manuscript introduces a rational method to determine the appropriated insulin replacement when high insulin antibodies levels are present.â¢This protocol provides instructions and details in mathematical tools and laboratory processes for the analysis of serum samples.â¢This method proved to be successful in a single case and requires confirmation using a large group of patients.
RESUMO
A melhor compreensão das causas da instabilidade dos níveis da glicemia em pacientes com diabetes melito tipo 1 (DMT1) e a disponibilidade de novas alternativas para enfrentá-la com sucesso, como a bomba de infusão contínua de insulina e os análogos das insulinas, tornaram relevante o questionamento sobre a existência do diabetes hiperlábil como uma entidade bem como a necessidade de defini-lo. O presente artigo pretendeu descrever o conceito de diabetes hiperlábil à luz dos novos avanços na terapia do DMT1 e propor critérios objetivos para a quantificação da labilidade da glicemia.
The best comprehension about the instability of the glycemia levels in type 1 diabetes mellitus (T1DM) patients and the availability of new alternatives to successfully control it, like insulin pump therapy and the insulin analogues, underlined the questions about the brittle diabetes existence as a clinical entity as well as the necessity of define it. The aim of this article was to describe the concept of brittle diabetes in the light of the latest advances in the treatment of type 1 diabetes and propose objective criteria to evaluate the level of glucose liability.
Assuntos
Humanos , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/terapia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêuticoRESUMO
O transplante de ilhotas é um procedimento em desenvolvimento, como alternativa para o tratamento do diabetes tipo 1 que está na fronteira entre o experimental e o clínico. É uma terapia celular na qual as células são implantadas em território diferente do fisiológico em que apenas determinado número incerto conseguirá se adaptar. Aperfeiçoar este processo para obter os mesmos resultados que no transplante de pâncreas, representa um desafio para o qual convergem contribuições da biologia celular, da imunologia e das técnicas de laboratório que se entrelaçam de maneira extremamente complexa. Este trabalho revisa a literatura expondo a evolução do procedimento, a sua metodologia atual e os resultados clínicos obtidos. As perspectivas futuras do transplante diante dos recentes avanços também são discutidas.
Islet transplant is an innovative treatment for type 1 diabetic patients, which still lies between experimental and approved transplant therapy. Islet cells are seeded in a non-physiological territory where an uncertain fraction will be able to adapt and survive. Thus, the challenge lies in improving the whole procedure, employing the tools of cell biology, immunology and laboratory techniques, in order to reach the results obtained with whole organ transplant. This review describes the procedure, its progress to the present methodology and clinical results obtained. Future perspectives of islet transplantation in the light of recent biotechnological advances are also focused.