Figure 2: Requirements for restoring beta-cell mass by stimulating beta-cell proliferation in type 1 diabetes.

To determine the prospects of restoring beta-cell mass via self-replication one needs to make several assumptions. Here we assumed that beta-cell mass increases with somatic growth during the first two decades of life, that residual beta-cell mass in long-standing diabetes is 5% and that the rate of beta-cell loss is lower in adult-onset type 1 diabetes. Although human beta-cell proliferation rates likely decline with age, we did not factor this into these scenarios. We further assume that beta-cell proliferation rate are similar across the pool of residual beta-cells in type 1 diabetes and did not account for a beta-cell refractory period, even though each beta-cell will have to complete the cell cycle multiple times in order to achieve restoration to even 25% of original beta cells mass starting from 5% of residual beta-cell mass. We further assumed a basal daily proliferation rate of 0.4%, based on published studies of primary human beta-cell basal proliferation in vitro. Such a daily proliferation rate is unlikely to offset the ongoing loss of beta-cell mass in early onset type 1 diabetes in a child who has not yet achieved their full beta-cell mass (Scenario 1). In adult onset type 1 diabetes with a slower rate of autoimmune-mediated beta cell loss (Scenario 2), a daily proliferation rate of 0.4% would gradually restore some functional beta-cell mass over the course of several years. Whether such a proliferation rate could be achieved in situ in the pancreas affected by type 1 diabetes is unknown and would depend on dosing with beta-cell mitogens that are weak and relatively non-specific over the course of many years, possible life-long, with any benefit to the individual not emerging until after years of medication adherence.