Treatment of type 1 diabetes mellitus to preserve insulin secretion

The idea of treating type 1 diabetes mellitus (T1D) with immunosup-pressive agents began with the recognition of this form of diabetes as a chronic autoimmune process [1]. Understanding of this process has been evolving, and with it, strategies for immune therapy. Unlike treatment with insulin, immune interventions are believed to affect the cause of the disease, but because newer data suggest a role for insulin in mediating b-cell survival and regeneration, metabolic treatment and immune intervention may need to be considered jointly. This article summarizes the evolution of current approaches to treatment and current controversies that attend these studies. Natural history of type 1 diabetes mellitus The autoimmune response that causes T1D begins years before clinical onset of disease, continues for years after diagnosis, and may recur years later if patients are rechallenged with an islet transplant. Initial pathologic studies of islets from patients with new-onset T1D suggested loss of approximately 90 % of insulin-positive cells [2]. Early studies by Faber and colleagues [3] showed that soon after diagnosis, the production of C-peptide in patients with diabetes consuming a standard diet was about one third of that seen in normal individuals. These studies measured 24-hour C-peptide levels, which provide only an estimate of insulin production. The inter-Endocrinol Metab Clin N Am 33 (2004) 93–111pretation that insulin secretion was impaired markedly at the time of di-agnosis with little evidence of recovery of b-cell mass was prevalent in the late 1980s and early 1990s. The potential benefits of immunosuppressiv