Effect of a Short-term Diet and Exercise Intervention on Serum Lipids, Oxidative Stress, Inflammation, and Monocyte Adhesion in Men with Type 2 Diabetes

2257 Atherosclerosis is accelerated in men with type 2 diabetes. Lifestyle factors may affect various components of the atherogenic process in diabetic men, including lipid levels, oxidative stress, inflammation and adhesive properties. PURPOSE: The present study was designed to examine the effects of a rigorous diet and exercise intervention on these components of atherosclerosis. METHODS: Diabetic men (n=10) 90% of whom had the metabolic syndrome (by WHO criteria), were placed on a high-fiber, low-fat diet in the Pritikin 3-week residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre and post fasting blood was drawn for determination of serum lipids, insulin, glucose, C-reactive protein (CRP), sE-selectin and 8-isoprostaglandin F2a (8-iso-PGF2a). In vitro studies were used to investigate factors affecting the monocyte/endothelial interaction, a key step in atherogenesis. Subject sera was incubated with human aortic endothelial cells (HAEC) to determine cell surface expression of vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule-1 (ICAM-1) and THP-1 (a monocytic cell line) adhesion to serum-stimulated HAEC cultures. Additionally, sera was incubated with cocultures of human aortic smooth muscle cells overlaid with HAEC to assess cellular production of monocyte chemoattractant protein-1 (MCP-1). RESULTS: After the 3 week intervention, significant reductions in weight (111.9 ± 6.4 to 107.1 ± 6.6 kg, p<0.001), total cholesterol (189 ± 10.1 to 146 ± 3.8 mg/dL, p<0.001), LDL-C (105 ± 9.7 to 76 ± 4.3 mg/dL, p<0.01), LDL:HDL ratio (2.50 ± 0.18 to 2.13 ± 0.15, p=0.066), insulin (33.8 ± 4.0 to 23.9 ± 3.4 mIU/mL, p<0.002), glucose (157.5 ± 10.0 to 126.7 ± 8.7 mg/dL, p<0.05), HOMA-IR (12.6 ± 1.6 to 7.7 ± 1.0, p<0.02), QUICKI (0.27 ± 0.01 to 0.29 ± 0.01, p<0.01), 8-iso-PGF2a (52.6 ± 27.3 to 17.5 ± 8.0 pg/mL, p<0.02), CRP (4.47 ± 0.78 to 3.23 ± 0.75 mg/dL, p<0.03), and sE-selectin levels (59.5 ± 6.3 to 49.9 ± 4.6 ng/mL, p<0.001) were noted. Sera from subjects post-intervention induced significant reductions in THP-1 adhesion (187.4 ± 17.8 to 147.2 ± 17.0 % of control, p<0.03), VCAM-1 expression (85.0 ± 2.2 to 76.6 ± 2.0 % of control, p<0.001), ICAM- 1 expression (144 ± 2.0 to 130 ± 1.6 % of control, p<0.001) and MCP-1 (78.4 ± 9.6 to 61.2 ± 2.8 ng/mL, p<0.05), in cell culture systems. CONCLUSIONS: A combination of diet and exercise improves lipid profiles, reduces oxidative stress, mitigates monocyteendothelial interactions and monocyte chemotaxis. Intensive lifestyle modification confers ubiquitous CAD risk factor reduction in diabetic men.