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

Diabetes Care. 2019 Sep;42(9):1809-1815. doi: 10.2337/dc19-0244. Epub 2019 Jul 18.


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: NCT00004992 NCT00038727.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / prevention & control
  • Female
  • Humans
  • Kidney Diseases / epidemiology
  • Kidney Diseases / etiology
  • Logistic Models
  • Male
  • Microvessels / metabolism*
  • Middle Aged
  • Odds Ratio
  • Peripheral Vascular Diseases / epidemiology*
  • Peripheral Vascular Diseases / etiology
  • Prediabetic State / blood*
  • Prediabetic State / complications
  • Prevalence
  • Retinal Diseases / epidemiology
  • Retinal Diseases / etiology


  • Blood Glucose

Associated data