脂締素之血漿濃度與代謝症候群及缺血性腦血管疾病之相關性研究

研究目的–脂締素 (Adiponectin) 是一種衍生自脂肪組織的脂肪細胞激素，具抗發炎及抗粥瘤性，並於動脈粥樣硬化起始及過程具保護作用。此研究探討脂締素血中濃度在代謝症候群組成因子及缺血性腦血管疾病之關係。材料及方法–此為疾病對照組研究，研究對象總共有 313 人 (對照組 108 人、第 2 型糖尿病組 106 人及缺血性腦血管疾病組 99 人) ，血漿中之脂締素濃度以酵素連結免疫吸附分析。結果–在第 2 型糖尿病病人，血漿中脂締素濃度比對照組還要低 (分別為 4.2±3.2 mg/ mL 與 21.6±12.4 mg/ mL， p < .0001) 。經校正年齡，性別，身體質量指數及抽煙狀態，血漿中脂締素於兩組之間仍具顯著差異。利用簡單線性迴歸分析結果顯示: 血漿中脂締素高密度脂蛋白及低密度脂蛋白呈正相關。相對的，血漿中的脂締素度與腰臀比值、抽菸狀態、舒張壓、空腹血糖，三酸甘油脂及血漿中的高敏感Ｃ-反應蛋白成負相關。以複線性迴歸分析校正年齡、性別、身體質量指數之影響，結果顯示血漿中的脂締素與腰臀比值、舒張壓、空腹血糖、三酸甘油脂、高密度脂蛋白及高敏感Ｃ-反應蛋白具獨立相關性。在 99 位缺血性腦血管疾病病人，血漿中脂締素濃度比 108 位對照組還要低 (分別為 4.6±4.4 mg/mL與 21.6±12.4 mg/mL， p < .0001)。經校正年齡，性別，身體質量指數，腰臀比及抽煙狀態，血漿中脂締素於兩組之間仍具顯著差異 (分別為5.1 mg/mL與21.7 mg/mL， p < .0001)。於簡單邏輯式回歸分析發現，身體質量指數、腰臀比、收縮壓、舒張壓、空腹血糖、三酸甘油脂、高密度脂蛋白、肌酸酐、血漿中的高敏感Ｃ-反應蛋白、脂締素及抽菸狀態為缺血性腦血管疾病之預測指標，為避免危險因子之干擾，以邏輯迴歸分析校正年齡、性別、身體質量指數、腰臀比的影響，結果顯示抽煙、舒張壓、空腹血糖、高密度脂蛋白、血漿中的高敏感Ｃ-反應蛋白及脂締素皆為缺血性腦血管疾病之重要獨立因子。在複邏輯式迴歸分析，於研究群中我們以濃度較高的第一分位數 (23.0–49.5 mg/mL) 其勝算比為1 來比較其它的二、三、四分位數，校正其他危險因子包括年齡，身體質量指數，腰臀比，舒張壓，收縮壓，高密度脂蛋白，肌酸酐，血漿中之高敏感Ｃ-反應蛋白及抽菸狀態的影響，結果顯示其Odds ratio逐漸增加分別為 48.0 (95% CI，2.1–1092.7)，673.5 (95% CI，74.1–6117.2)，1163.2 (95% CI，26.9–15046.4)。結論–本研究顯示脂締素與肥胖、高血壓、高血脂、高血糖、不良脂血症及高敏感Ｃ-反應蛋白密切相關，且於第 2 型糖尿病及缺血性腦血管疾病血漿中之脂締素明顯下降，脂締素在國人代謝症候群、第2型糖尿病及缺血性腦血管疾病之致病機轉上有其角色。

關鍵字

脂締素；缺血性腦血管疾病；代謝症候群

並列摘要

Objectives: Adiponectin, an adipocyte derived peptide with anti-inflammatory and anti-therogenic effects, is known to protect against the initiation and progression of atherosclerosis. In this study, we investigate whether hypoadiponectinemia is present in patients with metabolic syndrome and ischemic cerebrovascular disease (CVD). Methods and Results: In this case–control study, plasma adiponectin concentration was measured by an ELISA method in type 2 diabetic and ischemic cerebrovascular disease. and healthy volunteers (controls group). The mean plasma level of adiponectin of the 106 patients with type 2 diabetic was significantly lower than that of 108 controls group (4.2±3.2 µg/mL versus 21.6 ±12.4 µg/mL, p<.0001). The plasma adiponectin levels remained significantly lower after adjustment for age, sex, BMI (body mass index), WHR (waist to hip ratio) and smoking status (4.3 µg/mL vs. 21.7 µg/mL, p<.0001)。 Plasma adiponectin level was positively correlated with age, total choleaterol, HDL-C (High density lipoprotein cholesterol) and LDL-C (Low density lipoprotein cholesterol) levels. In contrast, plasma adiponectin concentration was inversely correlated with smoking status, WHR, diastolic blood pressure (DBP), fasting plasma glucose (FPG), serum triglyceride (TG), and plasma hsCRP levels. Multiple linear regression analysis reverealed WHR, DBP, FPG, TG, HDL-C and hsCRP levels were independently associated with plasma adiponectin levels. The mean plasma level of adiponectin of 99 patients with ischemic cerebrovascular disease. was significantly lower than that of 108 controls group (4.6±4.4 µg/mL versus 21.6±12.4 µg/mL, p<.0001). The plasma adiponectin levels remained significantly lower after adjustment for age, sex, BMI, WHR, diabetes and smoking status (5.1 µg/mL vs 21.7 µg/mL, p<.0001).The mean plasma adiponectin level of men (20.6 ±12.9 µg/L) was not different from that of women (21.8±12.3 µg/L, p = ns). Logistic regression analysis found that BMI, WHR, SBP, DBP, FPG, TG, serum HDL-C and creatinine levels, smoking status, and plasma adiponectin and hsCRP levels to be predictors of ischemic cerebrovascular disease. Multiple logistic regression analysis revealed that DBP, serum FPG, HDL-C and creatinine levels, hsCRP, smoking status, and plasma adiponectin concentration to be independently correlated with ischemic cerebrovascular disease. Decreasing concentrations of adiponectin were independently and significantly associated with a higher risk of ischemic cerebrovascular disease when concentrations were analyzed both by quartile and as a continuous variable. The multiple logistic regression analysis adjusted odds ratios for ischemic cerebrovascular disease in the second, third, and fourth quartiles were 48.0 (95% CI,2.1–1092.7),673.5(95% CI, 74.1–6117.2), and 1163.2(95% CI,26.9–15046.4), respectively. In conclusion, the present report shows that plasma adiponectin concentration is low in patients with type 2 diabetes and ischemic cerebrovascular disease and it finds a possible close relationship between adiponectin–metabolic syndrome–inflammation and the development of atherosclerosis.