Therapies aimed at preservation or restoration of beta cell function in type 1 diabetes.
Type 1 diabetes is caused by an immune mediated destruction of the insulin-secreting beta cells in the pancreas. The disease can become clinically apparent at any age. At clinical diagnosis, there is invariably some residual beta cell function. Recent studies--including one mainly conducted in Belgium--have provided proof of principle that short-term humanized anti-T-cell antibody treatment is able to preserve residual beta cell function for at least 18 months in adult type 1 diabetic patients with a recent clinical onset of disease. The effect of anti-T-cell antibody treatment is more pronounced among patients with initial higher residual beta-cell function. The resultant stabilizing effect on metabolic control is expected to delay chronic complications and avoid hypoglycemia in these patients. With a similar goal in mind, non-uremic C-peptide negative type 1 diabetic patients are offered beta cell transplantation. During the last years the one year survival of these grafts under immune suppression with Anti-Thymocyte-Globulin, tacrolimus and mycophenolate mofetil exceeds 80% with virtually no cases of primary non-function. Widespread application will however only occur if ways are found to induce operational graft tolerance and the shortage of viable human donor cells can be overcome. Both islet xenotransplantation and stem cell therapy provide possible strategies to solve this problem and represent areas of intense investigation. The ultimate goal is prevention of clinical disease. Studies by the Belgian Diabetes Registry and others in first degree family members of type 1 diabetic patients have refined identification of individuals at very high risk of hyperglycemia so that new immunological treatments can be tested in the prediabetic phase.
Keymeulen
B
B
UZ Brussel and Diabetes Research Center, VUB, Laarbeeklaan 103, B 1090 Brussel.
D000911:Antibodies, Monoclonal / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control* / Q000628:therapy*; D018450:Disease Progression; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D010186:Pancreatic Function Tests; D011322:Primary Prevention; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal