Ronald B Goldberg1, Marinella Temprosa2, Lisa Mele2, Trevor Orchard3, Kieren Mather4, George Bray5, Edward Horton6, Abbas Kitabchi7, Jonathan Krakoff8, Santica Marcovina9, Leigh Perreault10, Neil White11. 1. Diabetes Research Institute, University of Miami, 1450 NW 10th Avenue, Suite 2054, Miami, FL, 33136. Electronic address: dppmail@bsc.gwu.edu. 2. The George Washington University, Biostatistics Center, 6110 Executive Blvd, Suite 750, Rockville, MD, 20852. 3. University of Pittsburgh, 3512 Fifth Avenue, Pittsburgh, PA, 15213. 4. Department of Medicine, Indiana University, 541 Clinical Drive CL 365, Indianapolis, IN, 46202. 5. Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Rd, Baton Rouge, LA, 70808. 6. Section on Clinical, Behavioral & Outcomes Research, Joslin Diabetes Center, One Joslin Place, Boston, MA, 02215; Department of Medicine, Harvard Medical School, 25 Shattuck St, Boston, MA, 02115. 7. Division of Endocrinology, University of Tennessee Health Science Center, 920 Madison Ave Suite 300A, Memphis, TN, 38163. 8. National Institute of Diabetes and Digestive and Kidney Diseases, 1550 E. Indian School Road, Phoenix, AZ, 85014. 9. University of Washington, Northwest Lipid Research Labs, 401 Queen Anne Avenue, North Seattle, WA, 98109. 10. Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, 12801 E. 17th Ave., Aurora, CO, 80045. 11. Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO, 63110.
Abstract
OBJECTIVE: In addition to slowing diabetes development among participants in the Diabetes Prevention Program (DPP), intensive lifestyle change and metformin raised HDL-cholesterol (HDL-C) compared to placebo treatment. We investigated the lifestyle and metabolic determinants as well as effects of biomarkers of inflammation, endothelial dysfunction and coagulation and their changes resulting from lifestyle and metformin interventions on the increase in HDL-C in the DPP. METHODS: The effects of a 1year period of intensive lifestyle change aimed at achieving 7% weight loss or metformin 850mg twice daily versus placebo on HDL-C were assessed in 3070 participants with impaired glucose tolerance, and on HDL particle concentration (HDL-P) and size in a subgroup of 1645 individuals. Treatment-associated changes in lifestyle and metabolic factors as well as in novel biomarkers were investigated for their associations with change in HDL-C using multiple regression analysis. RESULTS: After adjusting for BMI, insulin resistance, glycemia, dietary saturated fat, alcohol intake, physical activity and nine different biomarkers, only adiponectin accounted for the effect of intensive lifestyle change on HDL-C via an increase in large HDL-P. By contrast baseline and change in BMI and tissue plasminogen activator levels attenuated the effect of metformin on HDL-C, with adiponectin having no specific effect. CONCLUSION: While both lifestyle and metformin interventions used to prevent diabetes increase HDL-C, the mechanisms involved differ between the two treatments and may have consequences for future risk of cardiovascular disease.
RCT Entities:
OBJECTIVE: In addition to slowing diabetes development among participants in the Diabetes Prevention Program (DPP), intensive lifestyle change and metformin raised HDL-cholesterol (HDL-C) compared to placebo treatment. We investigated the lifestyle and metabolic determinants as well as effects of biomarkers of inflammation, endothelial dysfunction and coagulation and their changes resulting from lifestyle and metformin interventions on the increase in HDL-C in the DPP. METHODS: The effects of a 1year period of intensive lifestyle change aimed at achieving 7% weight loss or metformin 850mg twice daily versus placebo on HDL-C were assessed in 3070 participants with impaired glucose tolerance, and on HDL particle concentration (HDL-P) and size in a subgroup of 1645 individuals. Treatment-associated changes in lifestyle and metabolic factors as well as in novel biomarkers were investigated for their associations with change in HDL-C using multiple regression analysis. RESULTS: After adjusting for BMI, insulin resistance, glycemia, dietary saturated fat, alcohol intake, physical activity and nine different biomarkers, only adiponectin accounted for the effect of intensive lifestyle change on HDL-C via an increase in large HDL-P. By contrast baseline and change in BMI and tissue plasminogen activator levels attenuated the effect of metformin on HDL-C, with adiponectin having no specific effect. CONCLUSION: While both lifestyle and metformin interventions used to prevent diabetes increase HDL-C, the mechanisms involved differ between the two treatments and may have consequences for future risk of cardiovascular disease.
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