Approaches of Type 1 diabetes

Approaches to interdicting type 1 diabetes

Type 1 diabetes is characterized by immunemediated pancreatic islet β-cell destruction. The process is insidious and may evolve over many years, with the overt expression of clinical symptoms becoming apparent only when most β-cells have been destroyed. Much investigation has been directed at interdicting the type 1  diabetes disease process either by intervening during the stage of evolution of the diabetes disease to prevent it from becoming clinically manifest

Individuals at high risk of type 1 diabetes, with the goal of arresting immune destruction and thus preventing or delaying the clinical onset of type 1 diabetes. Based on studies in animal models of type 1 diabetes, particularly the non-obese diabetic (NOD) mouse and the Biobreeding rat, many strategies have been proposed to alter the course of type 1 diabetes.

 

The strategies that have been tested in human beings fall into a few general categories:

(1) antigen- specific interventions, using insulin or related peptides, glutamic acid decarboxylase (GAD) or a component of heat-shock protein;

(2) immunosuppressive interventions, using agents such as cyclosporin, azathioprine, antithymocyte globulin, mycophenolate mofetil or cyclophosphamide;

(3) immunomodulatory interventions, using agents such as anti-CD3 monoclonal antibodies.This paper discusses the results to date of these approaches to interdict the type 1 diabetes process in human beings.

High risk of type 1 diabetes

Trials in individuals at risk of type 1 diabetes have been conducted with relatively safe interventions due to the fact that these individuals do not yet have clinical disease. Two large multicenter randomized controlled clinical trials have evaluated the effects of nicotinamide in high-risk relatives of individuals with type 1 diabetes.  Several trials have used insulin in an attempt to delay or prevent the onset of type 1 diabetes.

The Diabetes Prevention Trial–Type 1 (DPT-1) studied parenteral insulin in individuals with a projected 5-year risk of type 1 diabetes of at least 50% and oral insulin in individuals with a projected 5-year risk of type 1 diabetes of 25–50% . Unfortunately, parenteral insulin did not slow or prevent type 1 diabetes .  As a consequence, subjects with characteristics similar to those of that subgroup are being studied in a new oral insulin trial by the Type 1 Diabetes.

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