Regression From Prediabetes to Normal Glucose Regulation and Prevalence of Microvascular Disease in the Diabetes Prevention Program Outcomes Study (DPPOS)

Abstract

Objective: Regression from prediabetes to normal glucose regulation (NGR) was associated with reduced incidence of diabetes by 56% over 10 years in participants in the Diabetes Prevention Program Outcomes Study (DPPOS). In an observational analysis, we examined whether regression to NGR also reduced risk for microvascular disease (MVD).

Research design and methods: Generalized estimating equations were used to examine the prevalence of aggregate MVD at DPPOS year 11 in people who regressed to NGR at least once (vs. never) during the Diabetes Prevention Program (DPP). Logistic regression assessed the relationship of NGR with retinopathy, nephropathy, and neuropathy, individually. Generalized additive models fit smoothing splines to describe the relationship between average A1C during follow-up and MVD (and its subtypes) at the end of follow-up.

Results: Regression to NGR was associated with lower prevalence of aggregate MVD in models adjusted for age, sex, race/ethnicity, baseline A1C, and treatment arm (odds ratio [OR] 0.78, 95% CI 0.65-0.78, P = 0.011). However, this association was lost in models that included average A1C during follow-up (OR 0.95, 95% CI 0.78-1.16, P = 0.63) or diabetes status at the end of follow-up (OR 0.92, 95% CI 0.75-1.12, P = 0.40). Similar results were observed in examination of the association between regression to NGR and prevalence of nephropathy and retinopathy, individually. Risk for aggregate MVD, nephropathy, and retinopathy increased across the A1C range.

Conclusions: Regression to NGR is associated with a lower prevalence of aggregate MVD, nephropathy, and retinopathy, primarily due to lower glycemic exposure over time. Differential risk for the MVD subtypes begins in the prediabetes A1C range.

Trial registration: ClinicalTrials.gov NCT00004992 NCT00038727.

Figure 1

Predicted, unadjusted prevalence of aggregate MVD (retinopathy, nephropathy, and/or neuropathy) (A), nephropathy (B), retinopathy (C), and neuropathy (D) as a function of A1C levels during DPPOS follow-up. Solid lines represent a smoothed, fitted relationship, whereas the dotted lines represent the pointwise 95% CI.

Figure 2

A1C over DPP and DPPOS for participants who ever versus never regressed from prediabetes to normoglycemia (includes those who have and have not developed diabetes). BAS, baseline.