[Clinical study of the month. Attempt at preservation of B cells during the initial phase of type 1 diabetes: negative results with ultralente insulin, but promising results with an anti-CD3 monoclonal antibody].
Type 1 diabetes is an autoimmune disease leading to a progressive exhaustion of the insulin secretion and a destruction of the B-cells. Attempts of preservation of insulin-producing B-cells can be performed at an early, most often silent, stage of the disease in well-selected at high risk subjects or during the period immediately following the clinical diagnosis based upon classical signs of hyperglycaemia. In the "Diabetes Prevention Trial-Type 1", the prophylactic subcutaneous administration of low-dose ultralente insulin was not able to prevent the development of type 1 diabetes nor to preserve residual insulin secretion in young relatives at very high-risk of diabetes, selected upon genetic, immunological and metabolic criteria. In contrast, a pilot randomized trial shows that a treatment with a nonactivating humanized monoclonal antibody against CD3 mitigates the deterioration in insulin production and improves metabolic control, with lower dose of exogenous insulin, during the first year of type 1 diabetes mellitus in 9 out of 12 treated patients. Besides a better understanding of the natural history of the disease, these clinical trials open new perspectives for prevention of type 1 diabetes mellitus, currently assessed by the Belgian Diabetes Registry.
Service de Diabétologie, Nutrition et Maladies métaboliques, Département de Médecine, CHU Sart Tilman, Liège.
J C
JC
Philips
A J
AJ
Scheen
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting