Buldak Lukasz, Dulawa-Buldak Anna, Labuzek Krzysztof, Okopien Boguslaw
Department of Internal Medicine and Clinical Pharmacology, Silesian Medical University, Medykow 18, 40-752 Katowice, Poland.
Int J Clin Pharmacol Ther. 2012 Nov;50(11):805-13. doi: 10.5414/CP201735.
Concerns regarding worsening insulin sensitivity associated with statin treatment have recently emerged. Therefore the aim of this study was to assess and compare the effects of 90-day monotherapies with fenofibrate and atorvastatin, as well as combined therapy, on fasting plasma glucose, insulin resistance index, adipokines (leptin, resistin, adiponectin) and levels of proinflammatory cytokines (TNF-α, IL-6) in patients with impaired fasting glucose (IFG) and mixed hyperlipidemia.
67 patients were randomly assigned to four treatment arms: monotherapy with atorvastatin, monotherapy with fenofibrate, combined therapy (fenofibrate and torvastatin) or therapeutic lifestyle change. The study lasted for 90 days. All participants received counseling regarding proper diet and physical activity.
Compared to the control subjects, prediabetic patients exhibited elevated plasma levels of leptin, resistin, TNF-α and IL-6, and a lower plasma level of adiponectin. All therapeutic interventions resulted in significant alterations in the lipid profile. Insulin resistance index (HOMA-IR) was reduced after treatment with fenofibrate. The effect of atorvastatin on insulin resistance was comparable to therapeutic lifestyle change alone. Therapy with hypolipidemic drugs caused increases in adiponectin levels and decreases in leptin and resistin. An additive effect of the combined treatment on plasma IL-6 level was also observed.
Fenofibrate-based treatment was associated with improved insulin sensitivity. Atorvastatin did not cause a deterioration in insulin sensitivity. Hypolipidemic therapies resulted in significant changes in the proinflammatory cytokine network as well as in adipokine levels. At the end of the study the measured parameters nearly resembled those of the healthy subjects.
近期出现了关于他汀类药物治疗导致胰岛素敏感性恶化的担忧。因此,本研究的目的是评估和比较非诺贝特和阿托伐他汀90天单药治疗以及联合治疗对空腹血糖受损(IFG)合并混合性高脂血症患者的空腹血糖、胰岛素抵抗指数、脂肪因子(瘦素、抵抗素、脂联素)和促炎细胞因子水平(TNF-α、IL-6)的影响。
67例患者被随机分配到四个治疗组:阿托伐他汀单药治疗、非诺贝特单药治疗、联合治疗(非诺贝特和阿托伐他汀)或治疗性生活方式改变。研究持续90天。所有参与者均接受了关于合理饮食和体育活动的咨询。
与对照组相比,糖尿病前期患者的血浆瘦素、抵抗素、TNF-α和IL-6水平升高,血浆脂联素水平降低。所有治疗干预均导致血脂谱发生显著变化。非诺贝特治疗后胰岛素抵抗指数(HOMA-IR)降低。阿托伐他汀对胰岛素抵抗的影响与单纯治疗性生活方式改变相当。降脂药物治疗导致脂联素水平升高,瘦素和抵抗素水平降低。联合治疗对血浆IL-6水平也有相加作用。
基于非诺贝特的治疗与胰岛素敏感性改善相关。阿托伐他汀未导致胰岛素敏感性恶化。降脂治疗导致促炎细胞因子网络以及脂肪因子水平发生显著变化。在研究结束时,所测量的参数几乎与健康受试者的参数相似。