Department of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
J Clin Lipidol. 2013 Sep-Oct;7(5):446-53. doi: 10.1016/j.jacl.2013.04.004. Epub 2013 Apr 29.
Type 2 diabetes is associated with early development of endothelial dysfunction. Patients present with typical dyslipidemia (predominantly high levels of triglycerides [TG] and low levels of high-density lipoprotein cholesterol [HDL-C]) or mixed hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C] and TG with low HDL-C). Normal levels include LDL-C < 100 mg/dL, TG < 135 mg/dL, and HDL-C > 40 mg/dL for men and >50 mg/dL for women.
To determine the effects of 8 weeks' administration of fenofibrate on inflammatory markers, metabolic parameters, and endothelial dysfunction.
We administered micronized fenofibrate (Laboratories Fourneir S.A Dijon, France) daily for 8 weeks to 40 dyslipidemic, type 2 diabetes patients with equal numbers in each arm of the typical or mixed dyslipidemia groups. Noninvasive endothelial function assessments were performed and serum inflammatory markers obtained before and after treatment.
The typical group demonstrated significantly greater TG reduction and HDL-C increment, ie, 56% vs, 21.3% (P < .005) and 21% vs. 7.6% (P = .001), respectively, compared with the mixed group. There was greater LDL-C reduction within the mixed group compared with the typical group 21.0% vs. 2.2% (P < .05). Endothelial dysfunction was present in both groups at baseline. After treatment, the typical group demonstrated significant improvement in resting brachial diameter (3.9 mm [interquartile range {IQR} 3.3-4.7] to 4.2 mm [IQR 3.4-4.8], P = .001) compared with no change within the mixed group (3.6 mm [IQR 3.1-5.4] to 3.7 mm [IQR 3.1-5.3], P = .26). Flow-mediated diameter improved significantly in both groups. The mixed group had significantly greater levels of hs-CRP at baseline but no changes throughout the study. The mixed group demonstrated an increase in vascular adhesion molecule-1 from 706 ng/mL (IQR 566-1195) to 845 ng/mL (637-1653; P = .01), a reduction of tumor necrosis factor-α from 7.0 pg/mL (IQR 1.0-43.5) to 2.5 pg/mL (IQR 1.5-13.5; P = .04) throughout the study.
We effectively compared 8 weeks of fenofibrate therapy in type 2 diabetics with contrasting lipid abnormalities. The typical dyslipidemia group showed significantly greater lipid improvements compared with the mixed dyslipidemia group. Both groups had improvements in endothelial functions that were independent of the lipid levels. We concluded that fibrate therapy in type 2 diabetics is beneficial, especially those with typical dyslipidemia and extends beyond its lipid lowering properties.
2 型糖尿病与内皮功能障碍的早期发展有关。患者表现出典型的血脂异常（主要是甘油三酯 [TG] 水平升高和高密度脂蛋白胆固醇 [HDL-C] 水平降低）或混合性高胆固醇血症（低密度脂蛋白胆固醇 [LDL-C] 和 TG 水平升高，而 HDL-C 水平降低）。正常水平包括 LDL-C < 100mg/dL、TG < 135mg/dL 和 HDL-C > 40mg/dL（男性）和 >50mg/dL（女性）。
确定 8 周服用非诺贝特对炎症标志物、代谢参数和内皮功能障碍的影响。
我们每天给 40 名血脂异常的 2 型糖尿病患者服用微粉化非诺贝特（法国第戎 Fourneir 实验室）8 周，每组各有一半患者患有典型或混合性血脂异常。在治疗前后进行非侵入性内皮功能评估并检测血清炎症标志物。
典型组的 TG 降低和 HDL-C 升高幅度明显大于混合组，分别为 56%比 21.3%（P <.005）和 21%比 7.6%（P =.001）。与典型组相比，混合组的 LDL-C 降低更明显，为 21.0%比 2.2%（P <.05）。两组患者在基线时均存在内皮功能障碍。治疗后，典型组的静息肱动脉直径明显改善（3.9mm[四分位距 {IQR} 3.3-4.7]至 4.2mm[IQR 3.4-4.8]，P =.001），而混合组无变化（3.6mm[IQR 3.1-5.4]至 3.7mm[IQR 3.1-5.3]，P =.26）。两组的血流介导的直径均显著改善。混合组的 hs-CRP 水平在基线时明显较高，但在整个研究过程中没有变化。混合组的血管细胞黏附分子-1 从 706ng/ml（IQR 566-1195）增加到 845ng/ml（637-1653；P =.01），肿瘤坏死因子-α从 7.0pg/ml（IQR 1.0-43.5）减少到 2.5pg/ml（IQR 1.5-13.5；P =.04）。
我们有效地比较了 8 周非诺贝特治疗 2 型糖尿病伴不同脂质异常的效果。典型血脂异常组与混合血脂异常组相比，血脂改善更为显著。两组的内皮功能均有所改善，且独立于血脂水平。我们得出结论，纤维酸类药物治疗 2 型糖尿病是有益的，尤其是对具有典型血脂异常的患者，其益处超出了降低血脂的作用。
