Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory

Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with “brittle T1DM”, who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clínicas de Porto Alegre – Rio Grande do Sul, Brazil.

Genetics of diabetic nephropathy / Bases genéticas da nefropatia diabética

The increasing prevalence of diabetes mellitus has led to a growing number of chronic complications including diabetic nephropathy (DN). In addition to its high prevalence, DN is associated with high morbidity and mortality especially due to cardiovascular diseases. It is well established that genetic factors play a role in the pathogenesis of DN and genetically susceptible individuals can develop it after being exposed to environmental factors. DN is probably a complex, polygenic disease. Two main strategies have been used to identify genes associated to DN: analysis of candidate genes, and more recently genome-wide scan. Great efforts have been made to identify these main genes, but results are still inconsistent with different genes associated to a small effect in specific populations. The identification of the main genes would allow the detection of those individuals at high risk for DN and better understanding of its pathophysiology as well.

A crescente elevação na prevalência do diabetes melito (DM) acarretou em um aumento de suas complicações crônicas, entre elas a nefropatia diabética (ND). Além da elevada prevalência, a ND está associada à importante morbidade e mortalidade, principalmente por doenças cardiovasculares. É notória a contribuição genética na patogênese da ND, em que, na presença de fatores ambientais propícios, aqueles indivíduos geneticamente predispostos desenvolverão a doença. Trata-se de uma doença com provável transmissão genética do tipo poligênica e complexa. Duas estratégias principais têm sido utilizadas na busca dos genes associados à ND: a avaliação de genes candidatos e, mais recentemente, a utilização de genoma wide scan. Grande empenho tem sido realizado para identificar os principais genes associados à ND, mas os resultados ainda são heterogêneos com diferentes genes apresentando um efeito pequeno em populações específicas. A identificação dos principais genes permitiria prever os indivíduos de maior risco para o desenvolvimento da ND, além de possibilitar um melhor entendimento fisiopatológico da doença.