Normalization of plasma lipid peroxides, monocyte adhesion, and tumor necrosis factor-α production in NIDDM patients after gliclazide treatment
Normalization of plasma lipid peroxides, monocyte adhesion, and tumor necrosis factor-α production in NIDDM patients after gliclazide treatment
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DOI：
10.2337/diacare.21.4.487
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发表时间：
1998-04-01
期刊：
影响因子：
16.2
通讯作者：
Renier, G
中科院分区：
文献类型：
--
作者：
Desfaits, AC;Serri, O;Renier, G
目的 - 评估格列齐特对 NIDDM 患者给药对 1）单核细胞对培养内皮细胞的粘附，2）血浆细胞因子和脂质过氧化物水平，以及 3）单核细胞细胞因子产生的影响。 研究设计和方法 - 招募了控制不佳的格列本脲治疗糖尿病患者（n = 8）和健康对照受试者（n = 8）。在研究开始时，格列本脲被同等降血糖剂量的格列齐特取代。在用格列齐特治疗3个月之前和之后，从对照组和糖尿病受试者的血液中分离出血清和单核细胞。 结果-NIDDM患者的血浆脂质过氧化物水平和单核细胞与内皮细胞的粘附增强，并且格列齐特给药完全逆转了这些异常。在格列齐特治疗之前，除了NIDDM受试者中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL）-6的增强外，对照组和糖尿病组的细胞因子血清水平没有差异。基础和脂多糖 (LPS) 刺激的单核细胞产生白细胞介素 1β、IL-6 和 IL-8 在两组之间没有差异。此外，对照组和糖尿病组的基础单核细胞产生的 TNF-α 相似，而 NIDDM 组中观察到 LPS 刺激的单核细胞产生的 TNF-α 显着增加。格列齐特治疗可将糖尿病单核细胞 LPS 刺激的 TNF-α 产生降低至与对照受试者中观察到的水平相似。结论 - 给 NIDDM 患者服用格列齐特可抑制糖尿病单核细胞与内皮细胞的粘附性增加，并减少这些细胞产生 TNF-α。这些结果表明，用格列齐特治疗NIDDM受试者可能有益于预防与NIDDM相关的动脉粥样硬化。
OBJECTIVE - To evaluate the effect of gliclazide administration to NIDDM patients on 1) monocyte adhesion to cultured endothelial cells, 2) plasma cytokine and lipid peroxide levels, and 3) monocyte cytokine production.RESEARCH DESIGN AND METHODS - Poorly controlled glyburide-treated diabetic patients (n = 8) and healthy control subjects (n = 8) were recruited. At che beginning of the study, glyburide was replaced by an equivalent hypoglycemic dose of gliclazide. Serum and monocytes were isolated from blood obtained from control and diabetic subjects before and after 3 months of treatment with gliclazide.RESULTS - Plasma lipid peroxide levels and monocyte adhesion to endothelial cells are enhanced in NIDDM patients, and gliclazide administration totally reverses these abnormalities. Before gliclazide treatment, serum levels of cytokines did not differ in the control and the diabetic groups, with the exception of an enhancement of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL)-6 in NIDDM subjects. Basal and lipopolysaccharide (LPS)-stimulated monocyte production of interleukin-1 beta, IL-6, and IL-8 did not differ between the two groups. Furthermore, basal monocyte production of TNF-alpha was similar in the control and the diabetic groups, whereas a marked increase in the LPS-stimulated monocyte production of TNF-alpha was observed in the NIDDM group. Gliclazide treatment lowered LPS-stimulated TNF-alpha production by diabetic monocytes to levels similar to those observed in control subjects.CONCLUSIONS - Gliclazide administration to NIDDM patients inhibits the increased adhesiveness of diabetic monocytes to endothelial cells and reduces the production of TNF-alpha by these cells. These results suggest that treatment of NIDDM subjects with gliclazide may be beneficial in the prevention of atherosclerosis associated with NIDDM.