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 #
5U01DK048411-18
Application #
8033712
Study Section
Special Emphasis Panel (ZDK1-GRB-N (J1))
Program Officer
Linder, Barbara
Project Start
1994-08-20
Project End
2014-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
18
Fiscal Year
2011
Total Cost
$436,437
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Kim, Catherine; Aroda, Vanita R; Goldberg, Ronald B et al. (2018) Androgens, Irregular Menses, and Risk of Diabetes and Coronary Artery Calcification in the Diabetes Prevention Program. J Clin Endocrinol Metab 103:486-496
Ceglia, Lisa; Nelson, Jason; Ware, James et al. (2017) Association between body weight and composition and plasma 25-hydroxyvitamin D level in the Diabetes Prevention Program. Eur J Nutr 56:161-170
McCaffery, Jeanne M; Jablonski, Kathleen A; Franks, Paul W et al. (2017) Replication of the Association of BDNF and MC4R Variants With Dietary Intake in the Diabetes Prevention Program. Psychosom Med 79:224-233
Jiang, Yunna; Owei, Ibiye; Wan, Jim et al. (2016) Adiponectin levels predict prediabetes risk: the Pathobiology of Prediabetes in A Biracial Cohort (POP-ABC) study. BMJ Open Diabetes Res Care 4:e000194
Zhou, Kaixin; Yee, Sook Wah; Seiser, Eric L et al. (2016) Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin. Nat Genet 48:1055-1059
Kim, Catherine; Barrett-Connor, Elizabeth; Aroda, Vanita R et al. (2016) Testosterone and depressive symptoms among men in the Diabetes Prevention Program. Psychoneuroendocrinology 72:63-71
Walford, Geoffrey A; Ma, Yong; Clish, Clary et al. (2016) Metabolite Profiles of Diabetes Incidence and Intervention Response in the Diabetes Prevention Program. Diabetes 65:1424-33
Kim, C; Christophi, C A; Goldberg, R B et al. (2016) Adiponectin, C-reactive protein, fibrinogen and tissue plasminogen activator antigen levels among glucose-intolerant women with and without histories of gestational diabetes. Diabet Med 33:32-8
Aroda, Vanita R; Edelstein, Sharon L; Goldberg, Ronald B et al. (2016) Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab 101:1754-61
Goldberg, Ronald B; Temprosa, Marinella; Mele, Lisa et al. (2016) Change in adiponectin explains most of the change in HDL particles induced by lifestyle intervention but not metformin treatment in the Diabetes Prevention Program. Metabolism 65:764-75

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