飲用含糖飲料與血液中視網醇結合蛋白丁濃度 與青少年心血管及代謝風險因子相關

Consumption of Sugar-Sweetened Beverage and Circulating retinol-binding protein 4 levels connected to adolescent cardiometabolic risk components and metabolic syndrome

詹德富(Te-Fu Chan)

指導教授 ： 林志隆

高雄醫學大學/醫學院/醫學研究所/博士(2014年)

https://doi.org/10.6832/KMU.2014.00099

摘要

含糖飲料中之果糖，其代謝的過程會影響脂肪和尿酸的生成。本研究在探討台灣青少年族群中，飲用含糖飲料對於血清中脂質和視網醇結合蛋白丁濃度的影響。我們隨機地從一項大型的斷面研究中選出了200位青少年(包括98位男性和102位女性)，使用多變數回歸模型並且校正其共變數的方式，針對他們的人體測量參數和生化檢查的結果進行分析。增加含糖飲料的飲用量與腰圍、臀圍、體重指數、血清中尿酸、三酸甘油酯和視網醇結合蛋白丁的數值增加有相關性；青少年中每天飲用大於500毫升的含半糖或更多的高果糖飲料者，其血清之三酸甘油酯和視黃醇結合蛋白丁的數值分別為22.7毫克/分升和13.92毫微克/毫升，明顯高於不飲用的青少年；此外，在飲用高果糖的青少年中，有高尿酸血症者，比起沒有高尿酸血症者有較高的三酸甘油酯濃度（ 98.6對比81.6毫克/分升）；而在超重和肥胖的青少年中，飲用富含高果糖飲料與體重指數大於24，這兩個因素會產生交互作用而使得視網醇結合蛋白丁的濃度更加上升；再者，在飲用含高果糖飲料的青少年中，血液循環裡視網醇結合蛋白丁的數值和與體重有關的指標和三酸甘油酯以及尿酸的濃度呈現了明顯的相關性（r= 0.253至0.404 ），但在沒有飲用含高果糖飲料的青少年中並沒有發現此現象。飲用富含高果糖的飲料與血清中三酸甘油酯和視網醇結合蛋白丁濃度的上升有關。高尿酸血症可能會強化高果糖的攝入對於三酸甘油酯數值升高的影響，尤其在超重和肥胖青少年中，高的體重指數可能會影響循環中果糖造成視網醇結合蛋白丁濃度上升的作用。
視網醇結合蛋白丁被認為是肥胖與胰島素抗性的連結因子，我們藉由深入分析血液中視網醇結合蛋白丁濃度與心血管代謝症候群風險因子之相關性，進一步探討視網醇結合蛋白丁在青少年脂肪及心血管系統軸運作關係。我們對於由大型研究中隨機抽取272位青少年(132男生及140位女生)之心血管代謝症候群風險因子與視網醇結合蛋白丁濃度進行分析。資料採用的分析方法為首要成分因子群分析(Principal component analysis) 及多變數迴歸分析，首要成分因子群對12種心血關代謝症候群風險因子進行分析後，取得三個主要首要成分因子群，第一個首要成分因子群可以解釋38.7%的變異因素，其中視網醇結合蛋白丁與體重相關數據、三酸甘油脂、收縮壓及尿酸與代謝症候群及胰島素抗性成正相關。在有尿酸血症之青少年，於多變數差異分析模式下，第一首要成分因子群每一單位的改變，網醇結合蛋白丁濃度有明顯差異(男孩1.999 ng/dl ; 女孩 2.377 ng/dl)。但這些現象在無尿酸血症之青少年則不見此現象。視網醇結合蛋白丁濃度如果上升一個標準差，則代謝症候群及胰島素抗性風險值分別升高2.5倍及1.9倍。視網醇結合蛋白丁濃度與代謝症候群心血管風險因子及胰島素抗性有關，高尿酸血症對於視網醇結合蛋白丁濃度與代謝症候群心血管風險有加強的影響。

關鍵字

視網醇結合蛋白丁 ； 含糖飲料 ； 心血管代謝症候群風險 ； 青少年

並列摘要

The metabolic effect of fructose in sugar-sweetened beverages (SSB) has been linked to de novo lipogenesisand uric acid (UA) production. This study investigated the biological effects of SSB consumption on serum lipid profiles and retinol-binding protein 4 (RBP4) among Taiwanese adolescents. We evaluated the anthropometric parameters and biochemical outcomes of 200 representative adolescents (98 boys and 102 girls) who were randomly selected from a large-scale cross-sectional study. Data were analyzed using multiple regression models adjusted for covariates. Results: Increased SSB consumption was associated with increased waist and hip circumferences, body mass index (BMI) values and serum UA, triglyceride (TG) and RBP4 levels. Adolescents who consumed >500 ml/day of beverages half-to-heavily sweetened with high-fructose corn syrup (HFCS) exhibited TG and RBP4 levels 22.7 mg/dl and 13.92 ng/ml higher than non-drinkers, respectively. HFCS drinkers with hyperuricemia had higher TG levels than HFCS drinkers with normal UA levels (98.6 vs. 81.6 mg/dl). The intake of HFCS-rich SSBs and high value of BMI (≥24) interactively reinforced RBP4 levels among overweight/obese adolescents. Circulating RBP4 levels were significantly correlated with weight-related outcomes and TG and UA concentration among HFCS drinkers ( r= 0.253 to 0.404), but not among non-drinkers. In conclusion, high-quantity HFCS-rich beverage consumption is associated with higher TG and RBP4 levels. Hyperuricemia is likely to intensify the influence of HFCS-rich SSB intake on elevated TG levels, and in overweight and obese adolescents, high BMI may modify the action of fructose on higher circulating levels of RBP4.
RBP4 has been proposed to be a vital mediator connecting obesity and insulin resistance (IR). This study investigated the role of RBP4 in the adolescent “adipo-cardiovascular axis” by investigating the association of its circulating concentrations with cardiometabolic risk components and outcomes. We assessed the cardiometabolic risk factors and metabolic outcomes of 272 representative adolescents (132 boys and 140 girls) who were randomly selected from a large-scale cross-sectional study. Data were analyzed using principal component analysis and multivariate regression models adjusted for covariates. Three principal components were extracted from 12 cardiometabolic risk factors and the first principal component (PC1) accounted for 38.7% of the total variance. RBP4 levels were positively correlated to body-weight-related parameters, triglyceride, systolic blood pressure and uric acid in both sexes and to metabolic syndrome (MetS) and IR. Significant multivariate-adjusted differences at RBP4 levels (1.999 ng/dl in boys and 2.377 ng/dl in girls) for a one-unit increase in PC1 scores were found among adolescents with hyperuricemia, but not among those without. Circulating RBP4 levels were notably capable at discriminating the presence of MetS and IR. A one-standard deviation increment of RBP4 was associated with a 2.5- and 1.9-fold risk of contracting MetS and IR, respectively, and explained 5.5% and 13.7% of the excess risk of PC1 on these two metabolic disorders. In conclsion, circulating RBP4 levels are associated with combined-cardiometabolic risk components and adolescent MetS and IR. Hyperuricemia demonstrates clinical implications on the positive correlation between continuous cardiometabolic risk-scores and RBP4 levels.

並列關鍵字

retinol-binding protein 4 (RBP4) ； sugar-sweetened beverages (SSB) ； cardiometabolic risk ； adolescent

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