제2형 당뇨병 환자에서 Rosiglitazone 병용 투여에 의한 동맥경직도의 개선 효과
The peroxisome proliferator-activated receptor-γ agonist, Rosiglitazone, improves aortic wall stiffness in type 2 diabetic patients
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목적 : 당뇨병은 동맥경화의 중요한 위험인자이다. 인슐린 저항성을 개선시키는 새로운 치료제인 PPARγ agonist인 rosiglitazone이 혈당강하효과 외에도 지질대사이상의 개선, PAI-1과 섬유소원의 감소, 혈소판 응집능의 감소 등의 작용이 알려지고 있으며, 최근에는 동맥경화 예방에도 커다란 역할을 할 것으로 예측되고 있다. 그러나 rosiglitazone이 동맥 경직도에 미치는 직접적인 영향에 대한 연구는 아직까지 없다. 본 연구에서는 동맥 경직도를 평가할 수 있는 방법 중 하나인 맥파전도속도를 비침습적인 방법으로 측정하여 인슐린 비의존성 당뇨병 환자에서 rosiglitazone 병용에 의한 동맥 경직도에 미치는 영향을 살펴보고자 하였다. 방법 : 인슐린 비의존성 당뇨병 환자에서 GLIME군 20명(Glimepiride: 61.5±8.2세, M:F=9:11)과 ROSI군 20명(Rosiglitazone: 65.6±9.5세, M:F=4:16)을 대상으로 치료 시작 전과 치료 12개월째 PP-1000 (Hanbyul Meditech, Jeonju, Korea)을 이용하여 맥파전도속도를 측정하여 비교하였다. 모든 환자는 치료 시작 전과 치료 12개월 후 공복시 혈당, 당화혈색소, 혈중 콜레스테롤 농도, 간기능 수치, HOMAIR 및 hsCRP를 측정하였다. 결과 : GLIME군과 ROSI군 간의 임상적인 특징의 차이는 없었다. 기저치 carotid-femoral 맥파전도속도는 양 군 간에 차이가 없었으며(8.30±1.62 vs. 8.38±1.60 m/sec, p=0.879), 12개월 후 맥파전도속도는 GLIME군에서는 변화가 없었으나(8.30±1.62 vs. 8.29±1.25 m/sec, p=0.941), ROSI 군에서는 의의있게 감소하였다(8.38±1.60 vs. 7.26±1.49 m/sec, p=0.002). hsCRP의 변화 정도는 ROSI군에서 의미있게 감소하였다(2.68±4.53 vs. -0.50±0.93 mg/dL, p=0.007). 맥파전도속도의 변화 정도와 hsCRP 변화 정도는 양의 상관관계를 나타내었다(r=0.412, p=0.033). 결론 : 제2형 당뇨병 환자에서 rosiglitazone의 병용 투여에 의해 동맥경직도가 감소하였으며, hsCRP도 감소하였다. 이러한 결과는 rosiglitazone이 최소한 염증의 완화와 관련하여 동맥경직도의 개선과 관련이 있을 것으로 생각된다.
Abstract
Background : Diabetes is a major risk factor for the development of coronary artery disease. Atherosclerosis is thought to arise as a result of a chronic inflammatory process within the arterial wall. Insulin resistance is central to the pathogenesis of type 2 diabetes and may contribute to atherosclerosis, either directly or through associated risk factors. Rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist, is used in the treatment of type 2 diabetes mellitus, and previous findings suggest that it may have anti-inflammatory effects on atherosclerosis. This study was performed to evaluate whether rosiglitazone can improve arterial stiffness in type 2 diabetic patients. Methods : This study consisted of 40 patients with type 2 diabetes. These subjects were classified into two groups either medicated with glimepiride (GLIME group, 61.5±8.2 years, M:F = 9:11) or with glimepiride and rosiglitazone (ROSI group, 65.6±9.5 years, M:F = 4:16). For each group, plasma a hsCRP, lipid profile, HOMAIR and HbA1c were measured before and after 12 months of medical treatment. At the same time, pulse wave velocity (PWV) using an automatic device (PP 1000, Hanbyul, Jeonju, Korea) was measured. Results : The plasma hsCRP level was significantly decreased in the ROSI group as compared with the GLIME group (4.22±4.65 vs. 1.07±0.80 mg/L, p=0.025). The carotid-femoral PWV of the ROSI group improved significantly as compared with the GLIME group (8.29±1.25 vs. 7.26±1.49 m/sec, p=0.024). The changes of PWV were correlated with the changes of hsCRP (r=0.412, p=0.033). Conclusions : These findings suggest that rosiglitazone can improve the arterial stiffness in type 2 diabetic patients.(Korean J Med 72:376-383, 2007)
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