Department of Internal Medicine, Mayo School of Graduate Medical Education, Mayo Clinic, Rochester, MN 55905, USA.
Mayo Clin Proc. 2012 Jun;87(6):561-70. doi: 10.1016/j.mayocp.2012.02.014.
To determine whether targeted pharmacological improvement of insulin sensitivity will normalize the associated elevations of thrombotic and inflammatory cardiovascular disease (CVD) biomarkers in individuals with insulin resistance.
Study 1 was a cross-sectional study of Asian Indians with and without diabetes mellitus and Northern European Americans without diabetes (n=14 each) conducted between December 11, 2003, and July 14, 2006. Study 2 was a secondary analysis of a double-blind randomized controlled study conducted between August 19, 2005, and August 24, 2010, that included 25 individuals with untreated diabetes or impaired fasting glucose who were randomized to receive placebo (n=13) or a combination of metformin, 1000 mg twice daily, and pioglitazone, 45 mg daily (n=12), for 3 months. In both studies, measurements of insulin sensitivity (euglycemic-hyperinsulinemic clamp) and plasma inflammatory and thrombotic factor concentrations were obtained on enrollment (studies 1 and 2) and after intervention (study 2).
Study 1 demonstrated significant correlations between insulin sensitivity and plasma adiponectin, high-density lipoprotein cholesterol, plasminogen activator inhibitor 1, interleukin 6, tumor necrosis factor α, and triglycerides. Insulin sensitizer therapy significantly improved insulin sensitivity, inflammatory cytokines except interleukin 6, and thrombotic factors except fibrinogen, without concomitant changes in weight, blood pressure, or body composition.
Insulin sensitizer therapy ameliorates inflammatory and thrombotic factors implicated in developing CVD. Interventions to improve insulin sensitivity may thus be considered as therapeutic options to reduce CVD burden in insulin-resistant states, although further research is needed to determine long-term effects on morbidity and mortality.
确定针对胰岛素敏感性的靶向药物改善是否会使胰岛素抵抗个体相关的血栓形成和炎症心血管疾病（CVD）生物标志物恢复正常。
研究 1 是一项在 2003 年 12 月 11 日至 2006 年 7 月 14 日之间进行的横断面研究，纳入了有或无糖尿病的亚洲印第安人和无糖尿病的北欧美国人（每组各 14 人）。研究 2 是对 2005 年 8 月 19 日至 2010 年 8 月 24 日进行的一项双盲随机对照研究的二次分析，该研究纳入了 25 例未经治疗的糖尿病或空腹血糖受损患者，将其随机分为安慰剂组（n=13）或二甲双胍 1000mg 每日两次和吡格列酮 45mg 每日一次组（n=12），治疗 3 个月。在这两项研究中，在入组时（研究 1 和 2）和干预后（研究 2）均测量了胰岛素敏感性（葡萄糖-高胰岛素正葡萄糖钳夹）和血浆炎症和血栓形成因子浓度。
研究 1 表明，胰岛素敏感性与血浆脂联素、高密度脂蛋白胆固醇、纤溶酶原激活物抑制剂 1、白细胞介素 6、肿瘤坏死因子α和甘油三酯之间存在显著相关性。胰岛素增敏剂治疗可显著改善胰岛素敏感性、除白细胞介素 6 以外的炎症细胞因子和除纤维蛋白原以外的血栓形成因子，而体重、血压或身体成分没有相应变化。
胰岛素增敏剂治疗可改善与 CVD 发病相关的炎症和血栓形成因子。因此，改善胰岛素敏感性的干预措施可被视为减轻胰岛素抵抗状态下 CVD 负担的治疗选择，尽管需要进一步研究以确定其对发病率和死亡率的长期影响。
