Abnormal regulation of glycemia (“dysglycemia”) has a very long time course, from the earliest
stage of pre-diabetes, to the onset of Type 2 diabetes (T2D), to the development of clinically
detectable microvascular changes and measurable atherosclerosis, to clinically manifest
complications with attendant morbidity and mortality. The Diabetes Prevention Program (DPP)
focused on the pre-diabetes stage of dysglycemia and demonstrated powerful beneficial effects
of lifestyle intervention (ILS) and metformin (MET), compared with placebo (PLBO), in
preventing or delaying the onset of T2D over a 3-year period in a high-risk population (n=3234).
The DPP also investigated and described the interventions, phenotypic and genotypic risk
factors associated with T2D development, the effects of the interventions in the setting of these
risk factors, the health economic implications of T2D prevention, and other outcomes of interest.
Based on these results, the DPP lifestyle program has been widely implemented. The DPP
Outcomes Study (DPPOS) has explored the longer-term effects of T2D prevention in the DPP
cohort, bridging the period between pre-diabetes and T2D, and has examined outcomes that
required more time to develop than the 3-years of DPP. DPPOS showed longer-term salutary
effects of the original interventions on T2D prevention and on cardiovascular disease (CVD) risk
factors. The risk for microvascular disease was significantly greater in subjects who developed
T2D and increased with longer duration and higher hemoglobin A1c (HbA1c). There were no
significant differences by treatment group in the prevalence of the aggregate microvascular
outcome; however, compared with PLBO and MET, ILS significantly reduced the risk of
microvascular disease among women and those with HbA1c =6.5%.
During the one-year extension of DPPOS Phase 3, we will maintain and continue to follow the
well-characterized and valuable DPPOS cohort, and collect measurements of outcomes as
described in the protocol. We will 1) perform new analyses to characterize the heterogeneous
course of dysglycemia and its long-term complications and factors that define susceptibility or
resistance to diabetes, its complications, and common chronic conditions of aging, and 2)
explore the factors associated with participant retention, adherence to the protocol and
completion of measurements, and determine if alternative methods can be implemented to
improve retention and adherence and to expand data collection. These aims will provide
important insights into prediabetes and diabetes and their long-term outcomes and could serve
the potential further study of the DPPOS cohort.