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

  • Perreault, Leigh1
  • Pan, Qing2
  • Schroeder, Emily B1, 3
  • Kalyani, Rita R4
  • Bray, George A5
  • Dagogo-Jack, Samuel6
  • White, Neil H7
  • Goldberg, Ronald B8
  • Kahn, Steven E9
  • Knowler, William C10
  • Mathioudakis, Nestoras4
  • Dabelea, Dana
  • 1 University of Colorado Anschutz Medical Campus, Aurora, CO.
  • 2 George Washington University, Rockville, MD [email protected]
  • 3 Kaiser Permanente Colorado, Aurora, CO.
  • 4 Johns Hopkins University, Baltimore, MD.
  • 5 Pennington Biomedical Research Center, Baton Rouge, LA.
  • 6 University of Tennessee, Memphis, TN.
  • 7 Washington University in St. Louis, St. Louis, MO.
  • 8 University of Miami, Miami, FL.
  • 9 VA Puget Sound Health Care System and University of Washington, Seattle, WA.
  • 10 National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
Published Article
Diabetes care
Publication Date
Sep 01, 2019
DOI: 10.2337/dc19-0244
PMID: 31320445


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). 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. 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. 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. © 2019 by the American Diabetes Association.

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