We can change the natural history of type 2 diabetes

Abstract

As diabetes develops, we currently waste the first ∼10 years of the natural history. If we found prediabetes and early diabetes when they first presented and treated them more effectively, we could prevent or delay the progression of hyperglycemia and the development of complications. Evidence for this comes from trials where lifestyle change and/or glucose-lowering medications decreased progression from prediabetes to diabetes. After withdrawal of these interventions, there was no "catch-up"-cumulative development of diabetes in the previously treated groups remained less than in control subjects. Moreover, achieving normal glucose levels even transiently during the trials was associated with a substantial reduction in subsequent development of diabetes. These findings indicate that we can change the natural history through routine screening to find prediabetes and early diabetes, combined with management aimed to keep glucose levels as close to normal as possible, without hypoglycemia. We should also test the hypothesis with a randomized controlled trial.

© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1

Diagram illustrating the natural history of diabetes (progression from prediabetes to diabetes and development of diabetes complications over time) without interventions (A); with interventions such as lifestyle change or a glucose-lowering medication that are successful in decreasing progression from prediabetes to diabetes, but then are stopped (B); and with interventions that are titrated to keep glucose and A1C levels in the normal range and are not stopped (C).

Figure 2

Cumulative diabetes incidence in the DREAM study, where subjects with prediabetes were given rosiglitazone or placebo, including time points before and after the primary study was stopped (vertical dashed line). Adapted with permission from Gerstein et al. (32).

Figure 3

Cumulative diabetes incidence in the U.S. DPP study, showing subjects with prediabetes who were given troglitazone or placebo, including time points before and after the primary study was stopped (vertical dashed line). Adapted with permission from Knowler et al. (33).

Figure 4

Cumulative diabetes incidence in the U.S. DPP study, showing subjects with prediabetes who were given troglitazone or placebo, including only time points after the primary study was stopped on 4 June 1988. Adapted with permission from Knowler et al. (33).

Figure 5

Cumulative incidence of severe diabetic retinopathy in the Da Qing study, showing subjects with prediabetes who were randomized to receive instruction in diet + exercise or to be control subjects, including time points before and after the primary study was stopped (vertical dashed line). Adapted with permission from Gong et al. (34).