Abstract
Background: Since HOMA-IR predicts coronary artery calcification incidence and progression, but not independently of metabolic syndrome (MS), we sought to determine whether insulin resistance (IR) could be lowered by a phytochemical approach. In a 2-month clinical pilot study with Ginkgo biloba (EGb 761, 2 × 120 mg/d) on 11 MS patients, a novel biomarker spectrum embracing parameters of plaque formation, stability and progression, oxidative stress, inflammation, lipid composition and second messengers, made point-of-care theranostics feasible. Methods: Laser ellipsometry, photometric methods, ELISAs and EIAs were applied. Results: Nanoplaque formation was reduced by 14.3% (p < 0.01), nanoplaque size by 23.4% (p < 0.0004), oxLDL/LDL 21.0% (p < 0.002), 8- iso -PGF 2α 39.8% (p < 0.003), MPO 29.6% (p < 0.01), IL-6 12.9% (p < 0.04), hs-CRP 39.3% (p < 0.005), Lp(a) 26.3% (p < 0.001), MMP-9 32.9% (p < 0.04), whereas SOD was augmented 17.7% (p < 0.01), GPx 11.6% (p < 0.001), cAMP 43.5% (p < 0.001), and cGMP 32.9% (p < 0.001). Since none of the patients had a diabetes, we evaluated IR. Fasting morning glucose was reduced by 4.0% from 94.4 to 90.2 mg/dL (p < 0.03), insulin 8.6% from 12.7 to 11.5 mU/L (p < 0.04), and HOMA-IR 12.3% from 3.07 to 2.64 mU/L×mg/dL (p < 0.02). Because ginkgo is not an antidiabeticum, we looked out for a mechanistic explanation. Insulin (1), glucose (2) and HOMA-IR (3) were correlated to IL-6 (4), hs-CRP (5), TNFα (6) and TGFβ 1 (7), which changes in cytokine pattern could unravel lowering of the former quantities: 1 vs 4 (r = 0.73, p < 0.06); 2 vs 4 (r = 0.80, p < 0.03); 3 vs 4 (r = 0.71, p < 0.07); 1 vs 5 (r = 0.64, p < 0.03); 2 vs 5 (r = 0.75, p < 0.02); 3 vs 5 (r = 0.68, p < 0.14); 1 vs 6 (r = -0.68, p < 0.05); 2 vs 6 (r = -0.73, p < 0.04); 3 vs 6 (r = -0.67, p < 0.05); 1 vs 7 (r = -0.75, p < 0.09); 2 vs 7 (r = -0.70, p < 0.02) and 3 vs 7 (r = -0.89, p < 0.01). Conclusion: Ginkgo had beneficial effects on a multitude of arteriosclerotic and diabetic biomarkers. IR was diminished by 12.3% to an HOMA-IR markedly below 3 on average, a clinically tolerable level. Further, this decrease can explain the reduction in Ca 2+ -dependent nanoplaque formation and size. Thus, ginkgo may be used as complementary drug in the treatment of MS, arteriosclerotic and diabetic patients.
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