Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Department of Medicine, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, CO, USA.
J Investig Med. 2024 Mar;72(3):294-304. doi: 10.1177/10815589231225183. Epub 2024 Jan 18.
Dysmetabolic states, such as type 2 diabetes (T2D), characterized by insulin resistance (IR), are associated with fatty liver, increased cardiovascular disease (CVD) risk, and decreased functional exercise capacity (FEC). Rosiglitazone (RO) improves exercise capacity and IR in T2D. However, the effects of RO on FEC and other markers of CVD risk in prediabetes are unknown. We hypothesized that insulin sensitization with RO would improve exercise capacity and markers of CVD risk in participants with impaired glucose tolerance (IGT). Exercise performance (peak oxygen consumption and oxygen uptake kinetics), IR (homeostasis model assessment of IR and quantitative insulin sensitivity check index), and surrogate cardiovascular endpoints (coronary artery calcium (CAC) volume and density and C-reactive protein (CRP)) were measured in participants with IGT after 12 and 18 months of RO or placebo (PL). RO did not significantly improve exercise capacity. Glycemic measures and IR were significantly lower in people on RO compared to PL at 18 months. CAC volume progression was not different between PL and RO groups. RO did not improve exercise capacity during an 18-month intervention despite improved IR and glycemia in people with IGT. Future studies should explore why effects on FEC with RO occur in T2D but not IGT. Understanding these questions may help in targeting therapeutic approaches in T2D and IGT.
代谢异常状态，如 2 型糖尿病（T2D），其特征为胰岛素抵抗（IR），与脂肪肝、增加心血管疾病（CVD）风险和降低功能运动能力（FEC）有关。罗格列酮（RO）可改善 T2D 患者的运动能力和 IR。然而，RO 对糖尿病前期患者的 FEC 和其他 CVD 风险标志物的影响尚不清楚。我们假设 RO 对胰岛素敏感性的改善将提高糖耐量受损（IGT）参与者的运动能力和 CVD 风险标志物。在接受 RO 或安慰剂（PL）治疗 12 和 18 个月后，测量 IGT 参与者的运动表现（峰值耗氧量和摄氧量动力学）、IR（稳态模型评估的 IR 和定量胰岛素敏感性检查指数）和替代心血管终点（冠状动脉钙（CAC）体积和密度和 C 反应蛋白（CRP））。与 PL 相比，RO 组在 18 个月时的血糖和 IR 显著降低。PL 和 RO 组之间的 CAC 体积进展无差异。尽管 IGT 患者的 IR 和血糖得到改善，但 RO 在 18 个月的干预期间并未改善运动能力。未来的研究应该探讨为什么 RO 对 T2D 的 FEC 有影响，而对 IGT 没有影响。了解这些问题可能有助于针对 T2D 和 IGT 制定治疗方法。
