The Diabetes Prevention Program (DPP), a multi-center controlled clinical trial in a multiracial population of overweight persons with impaired glucose tolerance, established the efficacy of a life-style intervention aimed at a modest degree of weight loss and increased moderate-intensity activity, and of metformin in decreasing the development of diabetes by 58 and 31%, respectively. The DPP Outcome Study (DPPOS), a 10-year follow-up, was funded 1^2002 for a five-year period with the understanding that it would require refunding via competitive renewal. The overarching goal of DPPOS was to study whether the relatively shortterm benefits of delaying diabetes demonstrated in the DPP would translate into a more long-lasting impact that would reduce the public health burden of the diabetes epidemic. Specifically, DPPOS had the following major goals: 1) to determine the effects of DPP interventions on the long-term microvascular and cardiovascular disease (CVD) complications, atherosclerosis and CVD risk factors;2) to examine the long-term effects and durability of prior DPP interventions on further diabetes development;and 3) to describe the incidence of long-term complications and their risk factors in new onset type 2 diabetes and IGT. The DPPOS included an effort to maintain the original DPP metformin group on metformin and to continue a lifestyle intervention for the original lifestyle group. To date, after 10 years of DPP/DPPOS, 93% of the DPPOS cohort attends annual follow-up visits. A durable effect of diabetes prevention associated with the lifestyle and metformin interventions has been demonstrated with 36 and 19% reductions in diabetes incidence, respectively, compared with the placebo group. Interim analyses also reveal significant reductions in CVD risk factors in the intervention groups, with decreased utilization of medications. The development of diabetes is associated with an increased frequency of retinopathy and microalbuminuria. This application is designed to support completing the second five years of DPPOS focusing on complications that require more time to develop.

Public Health Relevance

The Diabetes Prevention Program (DPP) and first 5 years of the DPP Outcome Study (DPPOS) have demonstrated that a lifestyle intervention program aimed at weight loss, and metformin, prevent diabetes development over a 10 year period. Completion of DPPOS will examine the impact of diabetes prevention on long-term complications affecting the eye, kidney, nerves and heart, and remains critical to public health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK048339-17
Application #
7796767
Study Section
Special Emphasis Panel (ZDK1-GRB-N (J1))
Program Officer
Linder, Barbara
Project Start
1994-09-10
Project End
2014-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
17
Fiscal Year
2010
Total Cost
$481,190
Indirect Cost
Name
University of California San Diego
Department
Family Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Aroda, Vanita R; Knowler, William C; Crandall, Jill P et al. (2017) Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study. Diabetologia 60:1601-1611
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Mercader, Josep M; Liao, Rachel G; Bell, Avery D et al. (2017) A Loss-of-Function Splice Acceptor Variant in IGF2 Is Protective for Type 2 Diabetes. Diabetes 66:2903-2914
de Groot, Mary; Marrero, David; Mele, Lisa et al. (2017) Depressive Symptoms, Antidepressant Medication Use, and Inflammatory Markers in the Diabetes Prevention Program. Psychosom Med :
Rockette-Wagner, Bonny; Storti, Kristi L; Dabelea, Dana et al. (2017) Activity and Sedentary Time 10 Years After a Successful Lifestyle Intervention: The Diabetes Prevention Program. Am J Prev Med 52:292-299
Crandall, Jill P; Mather, Kieren; Rajpathak, Swapnil N et al. (2017) Statin use and risk of developing diabetes: results from the Diabetes Prevention Program. BMJ Open Diabetes Res Care 5:e000438
Luchsinger, José A; Ma, Yong; Christophi, Costas A et al. (2017) Metformin, Lifestyle Intervention, and Cognition in the Diabetes Prevention Program Outcomes Study. Diabetes Care 40:958-965
Goldberg, Ronald B; Aroda, Vanita R; Bluemke, David A et al. (2017) Effect of Long-Term Metformin and Lifestyle in the Diabetes Prevention Program and Its Outcome Study on Coronary Artery Calcium. Circulation 136:52-64
Kim, Catherine; Dabelea, Dana; Kalyani, Rita R et al. (2017) Changes in Visceral Adiposity, Subcutaneous Adiposity, and Sex Hormones in the Diabetes Prevention Program. J Clin Endocrinol Metab 102:3381-3389

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