基于代谢组学的膳食脂肪生物标志物及其与绝经后妇女慢性病风险的关联。
Metabolomics-Based Biomarker for Dietary Fat and Associations with Chronic Disease Risk in Postmenopausal Women.
机构信息
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, United States; School of Public Health, University of Washington, Seattle, WA, United States.
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, United States.
出版信息
J Nutr. 2023 Sep;153(9):2651-2662. doi: 10.1016/j.tjnut.2023.05.021. Epub 2023 May 26.
BACKGROUND
The Women's Health Initiative (WHI) randomized, controlled Dietary Modification (DM) trial of a low-fat dietary pattern suggested intervention benefits related to breast cancer, coronary heart disease (CHD), and diabetes. Here, we use WHI observational data for further insight into the chronic disease implications of adopting this type of low-fat dietary pattern.
OBJECTIVES
We aimed to use our earlier work on metabolomics-based biomarkers of carbohydrate and protein to develop a fat intake biomarker by subtraction, to use the resulting biomarker to develop calibration equations that adjusts self-reported fat intake for measurement error, and to study associations of biomarker-calibrated fat intake with chronic disease risk in WHI cohorts. Corresponding studies for specific fatty acids will follow separately.
METHODS
Prospective disease association results are presented using WHI cohorts of postmenopausal women, aged 50-79 y when enrolled at 40 United States clinical centers. Biomarker equations were developed using an embedded human feeding study (n = 153). Calibration equations were developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes were associated with cancer, cardiovascular diseases, and diabetes incidence in WHI cohorts (n = 81,954) over an approximate 20-y follow-up period.
RESULTS
A biomarker for fat density was developed by subtracting protein, carbohydrate, and alcohol densities from one. A calibration equation was developed for fat density. Hazard ratios (95% confidence intervals) for 20% higher fat density were 1.16 (1.06, 1.27) for breast cancer, 1.13 (1.02, 1.26) for CHD, and 1.19 (1.13, 1.26) for diabetes, in substantial agreement with findings from the DM trial. With control for additional dietary variables, especially fiber, fat density was no longer associated with CHD, with hazard ratio (95% confidence interval) of 1.00 (0.88, 1.13), whereas that for breast cancer was 1.11 (1.00, 1.24).
CONCLUSIONS
WHI observational data support prior DM trial findings of low-fat dietary pattern benefits in this population of postmenopausal United States women.
TRIAL REGISTRATION NUMBER
This study is registered with clinicaltrials.gov identifier: NCT00000611.
背景
妇女健康倡议（WHI）随机对照饮食干预试验（DM 试验）采用低脂饮食模式，该模式提示干预对乳腺癌、冠心病（CHD）和糖尿病有益。在这里，我们使用 WHI 观察性数据进一步深入了解采用这种低脂饮食模式对慢性疾病的影响。
目的
我们旨在使用之前关于碳水化合物和蛋白质的基于代谢组学的生物标志物的工作，通过减法开发一种脂肪摄入生物标志物，使用由此产生的生物标志物开发校准方程来调整自我报告的脂肪摄入以进行测量误差，并研究 WHI 队列中生物标志物校准的脂肪摄入与慢性疾病风险的关联。针对特定脂肪酸的相应研究将分别进行。
方法
前瞻性疾病关联结果使用 WHI 队列的绝经后妇女呈现，入组时年龄为 50-79 岁，在美国 40 个临床中心入组。生物标志物方程是使用嵌入的人体喂养研究（n = 153）开发的。校准方程是使用 WHI 营养生物标志物研究（n = 436）开发的。在大约 20 年的随访期间，将校准后的摄入量与 WHI 队列（n = 81,954）的癌症、心血管疾病和糖尿病发病率相关联。
结果
通过从一种物质中减去蛋白质、碳水化合物和酒精的密度来开发脂肪密度的生物标志物。开发了脂肪密度的校准方程。脂肪密度增加 20%的风险比（95%置信区间）为乳腺癌 1.16（1.06，1.27），冠心病 1.13（1.02，1.26），糖尿病 1.19（1.13，1.26），与 DM 试验的发现基本一致。在控制了其他饮食变量，特别是纤维后，脂肪密度与 CHD 不再相关，风险比（95%置信区间）为 1.00（0.88，1.13），而乳腺癌的风险比为 1.11（1.00，1.24）。
结论
WHI 观察性数据支持之前在该人群中的 DM 试验发现，低脂饮食模式对绝经后美国女性有益。
临床试验注册号
本研究在 clinicaltrials.gov 注册，注册号为 NCT00000611。
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