Regensteiner Judith G, Bauer Timothy A, Reusch Jane E B
Division of Internal Medicine, Center for Women's Health Research, Box B-180, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, CO 80262, USA.
Diabetes Care. 2005 Dec;28(12):2877-83. doi: 10.2337/diacare.28.12.2877.
Although exercise is recommended as a cornerstone of treatment for type 2 diabetes, it is often poorly adopted by patients. We have noted that even in the absence of apparent cardiovascular disease, persons with type 2 diabetes have an impaired ability to carry out maximal exercise, and the impairment is correlated with insulin resistance and endothelial dysfunction. We hypothesized that administration of a thiazolidinedione (TZD) agent would improve exercise capacity in type 2 diabetes.
Twenty participants with uncomplicated type 2 diabetes were randomly assigned in a double-blind study to receive either 4 mg/day of rosiglitazone or matching placebo after baseline measurements to assess endothelial function (brachial artery diameter by brachial ultrasound), maximal oxygen consumption (VO(2max)), oxygen uptake (VO(2)) kinetics, and insulin sensitivity by hyperinsulinemic-euglycemic clamp. Measurements were reassessed after 4 months of treatment.
Participant groups did not differ at baseline in any measure. Rosiglitazone-treated participants (n = 10) had significantly improved VO(2max) (19.8 +/- 5.3 ml . kg(-1) . min(-1) before rosiglitazone vs. 21.2 +/- 5.1 ml . kg(-1) . min(-1) after rosiglitazone, P < 0.01), insulin sensitivity, and endothelial function. A change in VO(2max) correlated with improved insulin sensitivity measured by clamp (r = 0.68, P < 0.05) and with improved brachial artery diameter (r = 0.70, P < 0.05). Placebo-treated participants (n = 10) showed no changes in VO(2max) (19.4 +/- 5.2 ml . kg(-1) . min(-1) before rosiglitazone vs. 18.1 +/- 5.3 ml . kg(-1) . min(-1) after rosiglitazone, NS) or brachial artery diameter.
This is the first known report showing that a TZD improved exercise function in type 2 diabetes. Whether this is due to the observed improvements in insulin sensitivity and/or endothelial function or to another action of the TZD class requires further exploration.
尽管运动被推荐为2型糖尿病治疗的基石，但患者往往难以坚持。我们注意到，即使在无明显心血管疾病的情况下，2型糖尿病患者进行最大运动量运动的能力也受损，且这种损害与胰岛素抵抗和内皮功能障碍相关。我们假设给予噻唑烷二酮（TZD）类药物会改善2型糖尿病患者的运动能力。
20例无并发症的2型糖尿病参与者在基线测量以评估内皮功能（通过肱动脉超声测量肱动脉直径）、最大耗氧量（VO₂max）、摄氧量（VO₂）动力学以及通过高胰岛素-正常血糖钳夹技术测定胰岛素敏感性后，被随机分配至双盲研究中，分别接受4mg/天的罗格列酮或匹配的安慰剂。治疗4个月后重新评估各项测量指标。
各参与者组在基线时的任何测量指标上均无差异。接受罗格列酮治疗的参与者（n = 10）的VO₂max显著改善（罗格列酮治疗前为19.8±5.3ml·kg⁻¹·min⁻¹，治疗后为21.2±5.1ml·kg⁻¹·min⁻¹，P < 0.01），胰岛素敏感性和内皮功能也有所改善。VO₂max的变化与通过钳夹技术测定的胰岛素敏感性改善相关（r = 0.68，P < 0.05），也与肱动脉直径的改善相关（r = 0.70，P < 0.05）。接受安慰剂治疗的参与者（n = 10）的VO₂max（罗格列酮治疗前为19.4±5.2ml·kg⁻¹·min⁻¹，治疗后为18.1±5.3ml·kg⁻¹·min⁻¹，无显著性差异）或肱动脉直径无变化。
这是已知的首份报告，表明TZD类药物可改善2型糖尿病患者的运动功能。这是由于观察到的胰岛素敏感性和/或内皮功能改善，还是TZD类药物的其他作用，尚需进一步探索。
