Ma Wenjie, Wu Jason H Y, Wang Qianyi, Lemaitre Rozenn N, Mukamal Kenneth J, Djoussé Luc, King Irena B, Song Xiaoling, Biggs Mary L, Delaney Joseph A, Kizer Jorge R, Siscovick David S, Mozaffarian Dariush
From the Department of Epidemiology, Harvard School of Public Health, Boston, MA (WM, QW, and DM); the Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA (DM); the Divisions of Aging (LD) and Cardiovascular Medicine and Channing Division of Network Medicine (DM), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; the Boston Veterans Affairs Healthcare System, Boston, MA (LD); the Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (KJM); The George Institute for Global Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia (JHYW); the Cardiovascular Health Research Unit, Departments of Medicine (RNL and DSS), Epidemiology (DSS), and Biostatistics (MLB), and the Collaborative Health Studies Coordinating Center (JAD), University of Washington, Seattle, WA; the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA (XS); the Department of Internal Medicine, University of New Mexico, Albuquerque, NM (IBK); and the Department of Medicine, Albert Einstein College of Medicine, Bronx, NY (JRK).
Am J Clin Nutr. 2015 Jan;101(1):153-63. doi: 10.3945/ajcn.114.092601. Epub 2014 Nov 12.
Experimental evidence suggests that hepatic de novo lipogenesis (DNL) affects insulin homeostasis via synthesis of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Few prospective studies have used fatty acid biomarkers to assess associations with type 2 diabetes.
We investigated associations of major circulating SFAs [palmitic acid (16:0) and stearic acid (18:0)] and MUFA [oleic acid (18:1n-9)] in the DNL pathway with metabolic risk factors and incident diabetes in community-based older U.S. adults in the Cardiovascular Health Study. We secondarily assessed other DNL fatty acid biomarkers [myristic acid (14:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and vaccenic acid (18:1n-7)] and estimated dietary SFAs and MUFAs.
In 3004 participants free of diabetes, plasma phospholipid fatty acids were measured in 1992, and incident diabetes was identified by medication use and blood glucose. Usual diets were assessed by using repeated food-frequency questionnaires. Multivariable linear and Cox regression were used to assess associations with metabolic risk factors and incident diabetes, respectively.
At baseline, circulating palmitic acid and stearic acid were positively associated with adiposity, triglycerides, inflammation biomarkers, and insulin resistance (P-trend < 0.01 each), whereas oleic acid showed generally beneficial associations (P-trend < 0.001 each). During 30,763 person-years, 297 incident diabetes cases occurred. With adjustment for demographics and lifestyle, palmitic acid (extreme-quintile HR: 1.89; 95% CI: 1.27, 2.83; P-trend = 0.001) and stearic acid (HR: 1.62; 95% CI: 1.09, 2.41; P-trend = 0.006) were associated with higher diabetes risk, whereas oleic acid was not significantly associated. In secondary analyses, vaccenic acid was inversely associated with diabetes (HR: 0.56; 95% CI: 0.38, 0.83; P-trend = 0.005). Other fatty acid biomarkers and estimated dietary SFAs or MUFAs were not significantly associated with incident diabetes.
In this large prospective cohort, circulating palmitic acid and stearic acid were associated with higher diabetes risk, and vaccenic acid was associated with lower diabetes risk. These results indicate a need for additional investigation of biological mechanisms linking specific fatty acids in the DNL pathway to the pathogenesis of diabetes.
实验证据表明，肝脏从头脂肪生成（DNL）通过饱和脂肪酸（SFA）和单不饱和脂肪酸（MUFA）的合成影响胰岛素稳态。很少有前瞻性研究使用脂肪酸生物标志物来评估与2型糖尿病的关联。
我们在心血管健康研究中，调查了美国社区老年成年人中DNL途径中的主要循环SFA[棕榈酸（16:0）和硬脂酸（18:0）]和MUFA[油酸（18:1n-9）]与代谢危险因素和新发糖尿病之间的关联。我们还次要评估了其他DNL脂肪酸生物标志物[肉豆蔻酸（14:0）、棕榈油酸（16:1n-7）、7-十六碳烯酸（16:1n-9）和反式vaccenic酸（18:1n-7）]，并估计了膳食SFA和MUFA。
在3004名无糖尿病的参与者中，于1992年测量了血浆磷脂脂肪酸，并通过药物使用和血糖确定新发糖尿病。通过重复的食物频率问卷评估日常饮食。多变量线性回归和Cox回归分别用于评估与代谢危险因素和新发糖尿病的关联。
在基线时，循环中的棕榈酸和硬脂酸与肥胖、甘油三酯、炎症生物标志物和胰岛素抵抗呈正相关（每项P趋势<0.01），而油酸通常显示出有益的关联（每项P趋势<0.001）。在30763人年期间，发生了297例新发糖尿病病例。在调整了人口统计学和生活方式后，棕榈酸（极端五分位数HR：1.89；95%CI：1.27，2.83；P趋势=0.001）和硬脂酸（HR：1.62；95%CI：1.09，2.41；P趋势=0.006）与较高的糖尿病风险相关，而油酸无显著关联。在次要分析中，反式vaccenic酸与糖尿病呈负相关（HR：0.56；95%CI：0.38，0.83；P趋势=0.005）。其他脂肪酸生物标志物以及估计的膳食SFA或MUFA与新发糖尿病无显著关联。
在这个大型前瞻性队列中，循环中的棕榈酸和硬脂酸与较高的糖尿病风险相关，而反式vaccenic酸与较低的糖尿病风险相关。这些结果表明需要进一步研究将DNL途径中特定脂肪酸与糖尿病发病机制联系起来的生物学机制。
