粘附因子與第二型糖尿病周邊血管病變之關聯

背景及目的 : 糖尿病的大血管病變是糖尿病致死及生活機能受影響的主因，如何阻止或延緩血管病變必需先明瞭有那些危險因子的存在，有所謂的傳統因子血壓、血脂、血糖等，非傳統硬化因子如高感度C-反應蛋白、胴胱胺和血管粘附分子等。以往的研究多着重於心臟或腦血管的問題，四肢周邊血管的部份則較少報告，但其造成相繼的臨床狀況如截肢，卻困擾著糖尿病患與醫護人員。本實驗利用周邊血管測定儀找出有無血管病變的糖尿病患者及無病史的健康受試者，企圖找尋血糖的控制、膽固醇、三酸甘油脂、微蛋白尿、粘附因子VCAM(vascular cell adhesion molecule)、ICAM(intercellular adhesion molecule)、E-selectin等與代表著血管硬化的脈波傳導速率PWV (Pulse Wave Velocity)和代表著血管病變的腳踝與上臂血壓的比值ABI之間的相關性。方法 :利用周邊血管測定儀做為篩檢工具，分成3組，糖尿病有周邊血管疾病者31人， 糖尿病無周邊血管疾病者41人及無糖尿病、高血壓及高血脂病史的健康檢查受測者31人，共103人，三組皆完成所有的粘附因子及血脂肪、血糖有關的檢測，包括E-selectin、 VCAM、 ICAM、總膽固醇、三酸甘油脂等。變異數分析ANOVA、事後檢定的Bonferroni 、t –test、皮爾森相關及一般線性模型的分析方法找出與ABI和PWV的影響的危險因子。當統計中的p值小於0.05則視為有顯著的統計差異。結果 : 年齡、脈波傳播速率PWV、三酸甘油脂、高密度脂蛋白膽固醇及粘附因子中的VCAM、E-selectin在各組之間有達到明顯的統計差異。其他抽煙、身體質量指數、膽固醇及ICAM等在三組間並未達明顯到統計差異。而在糖尿病有或無周邊血管病變的二組中，微蛋白尿有著統計差異，但與糖尿病罹病時間及糖化血紅素無統計差異。脈波傳播速率PWV在健康受試組、糖尿病有周邊血管病變、糖尿病無周邊血管病變分為1214.2+86.7cm/s、1724.9+497.1cm/s、1722.5+287.1cm/s。VCAM在健康受試組為503+147.8ng/dl、糖尿病無周邊血管病變是834.9+257.8ng/dl、糖尿病有周邊血管病變1054.7+438.2ng/dl。E-selectin在健康受試組為20.6+19.9ng/dl、糖尿病無周邊血管病變是56.3+20.3ng/dl、糖尿病有周邊血管病變77.1+33.4ng/dl。而ICAM在三組中並無差異存在。糖尿病無周邊血管病變組的微蛋白尿是266.4μg/mg、糖尿病有周邊血管病組為1121.9μg/mg，有統計意義的差別。影響脈波傳播速率中年齡為最大的變項，其次分別為膽固醇和ICAM，影響腳踝與上臂血壓的比值中E-selectin為最大的變項，其次為年齡。結論 : 糖尿病血管病變危險因子中發現年齡越老，VCAM及E-selectin濃度越高，脈波傳播速率越遠者較容易血管病變，而糖化血紅素、膽固醇、三酸甘油脂及微蛋白尿越低則較不易發生血管病變。

Background and purpose: Macrovascular complications are the main causes of death and morbidity among diabetic patients. To prevent or delay these complications, risk factors must be identified. Traditional risk factors include hypertension, hyperlipidemia, and hyperglycemia. There are also non-traditional risk factors, such as hs-CRP, homocysteine, and adhesion molecules. Prior studies have focused on cardiac and cerebrovascular diseases, while comparatively less attention has been given to peripheral vascular diseases. Nonetheless, sequelae such as limb amputation are disturbing to both patients and health professionals. This study employed a peripheral vascular screening device to search for PVD among diabetic and healthy individuals. We then attempted to find correlations between various biochemical markers (glycosylated hemoglobin, serum cholesterol, serum triglyceride, urine micro albuminuria, adhesion molecules VCAM and ICAM, and E-selectin) and the indicators of PVD, namely pulse-wave velocity (representing degree of arterial stiffness) and ankle-brachial index (representing degree of arterial occlusion).Methods: With the aid of a vascular screening device, a total of 103 subjects were divided into 3 groups: diabetics with PVD (31 subjects), diabetics without PVD (41 subjects), and healthy individuals without DM, hypertension, nor hyperlipidemia (31 subjects). All three groups completed blood tests for adhesion molecules, lipids, and glycemia, including E-selectin, VCAM, ICAM, total cholesterol, and triglyceride. Statistical analysis via ANOVA, Bonferroni, t-test, Pearson correlation, and linear regression model determined the risk factors that influence ABI and PWV.Results: The differences in age, pulse-wave velocity, triglyceride, VCAM, and e-selectin reached statistical significance between the three groups. Other factors such as smoking, BMI, cholesterol and ICAM were not significantly different between the groups. Between the two diabetic groups (with or without PVD) urine microalbuminuria was significantly different, but duration of DM and glycosylated hemoglobin were not significantly different. The PWV was 1214 ± 86.7cm/s in the control group, 1724 ± 497.1 cm/s in the DM with PAD group, and 1722 ± 287.1cm/s in the DM without PAD group. VCAM level was 503 ± 147.8 ng/dl in the control group, 834.9 ± 257.8 ng/dl in the DM without PAD group and 1054 ± 438.2 ng/dl in the DM with PAD group. E-selectin level was 20.6 ± 19.9 ng/dl in the control group, 56.3 ± 20.3 ng/dl in the DM without PAD group and 77.1 ± 33.4 ng/dl in the DM with PAD group. ICAM was not significantly different between the three groups. Urine microalbuminuria was 1121.9 μg/mg in the DM with PAD group, which was significantly higher than the 266.4 μg/mg found in the DM without PAD group. Factors with the greatest influence on PWV were age, cholesterol, and ICAM respectively. For ABI, e-selectin had the greatest influence, followed by age.Conclusion: Age, elevated VCAM, elevated e-selectin and high PWV are associated with higher risk for occlusive arterial diseases, whereas low levels of hemoglobin A1C, cholesterol, triglyceride, and urine microalbumin are associated with low risk.