Regression from prediabetes to normal glucose regulation is associated with reduction in cardiovascular risk: results from the Diabetes Prevention Program outcomes study

Abstract

Objective: Restoration of normal glucose regulation (NGR) in people with prediabetes significantly decreases the risk of future diabetes. We sought to examine whether regression to NGR is also associated with a long-term decrease in cardiovascular disease (CVD) risk.

Research design and methods: The Framingham (2008) score (as an estimate of the global 10-year CVD risk) and individual CVD risk factors were calculated annually for the Diabetes Prevention Program Outcomes Study years 1-10 among those patients who returned to NGR at least once during the Diabetes Prevention Program (DPP) compared with those who remained with prediabetes or those in whom diabetes developed during DPP (N = 2,775).

Results: The Framingham scores by glycemic exposure did not differ among the treatment groups; therefore, pooled estimates were stratified by glycemic status and were adjusted for differences in risk factors at DPP baseline and in the treatment arm. During 10 years of follow-up, the mean Framingham 10-year CVD risk scores were highest in the prediabetes group (16.2%), intermediate in the NGR group (15.5%), and 14.4% in people with diabetes (all pairwise comparisons P < 0.05), but scores decreased over time for those people with prediabetes (18.6% in year 1 vs. 15.9% in year 10, P < 0.01). The lower score in the diabetes group versus other groups, a declining score in the prediabetes group, and favorable changes in each individual risk factor in all groups were explained, in part, by higher or increasing medication use for lipids and blood pressure.

Conclusions: Prediabetes represents a high-risk state for CVD. Restoration of NGR and/or medical treatment of CVD risk factors can significantly reduce the estimated CVD risk in people with prediabetes.

Figure 1

Participant flow through DPP, DPPOS, and this study.

Figure 2

Trajectories of 10-year CVD risk during the DPPOS in people with diabetes (solid), prediabetes (medium dash), and NGR (short dash) represented by means (lines) and 95% CIs (gray dotted line) with adjustment for differences in treatment group, age at randomization, sex, race/ethnicity, and baseline CVD risk factors (TC concentration, SBP or use of antihypertensive medication, smoking status, diagnosis of diabetes, and/or HDL-C concentration).

Figure 3

Trends represented by means (lines) and 95% CIs (gray dotted line) for use of lipid-lowering medications (A), TC concentration (B), LDLconcentration (C), use of blood pressure–lowering medications (D), SBP (E), and DBP (F) over 10 years of the DPPOS in people with diabetes (solid), prediabetes (medium dash), and NGR (short dash) with adjustment for treatment group.