Abstract：
BACKGROUND: Psychological distress has been linked to diabetes risk. Few population-based, epidemiologic studies have investigated the potential molecular mechanisms (eg, metabolic dysregulation) underlying this association.
OBJECTIVE: To evaluate the association between a metabolomic signature for psychological distress and diabetes risk.
METHODS: We conducted a nested case-control study of plasma metabolomics and diabetes risk in the Nurses\' Health Study, including 728 women (mean age: 55.2 years) with incident diabetes and 728 matched controls. Blood samples were collected between 1989 and 1990 and incident diabetes was diagnosed between 1992 and 2008. Based on our prior work, we calculated a weighted plasma metabolite-based distress score (MDS) comprised of 19 metabolites. We used conditional logistic regression accounting for matching factors and other diabetes risk factors to estimate odds ratios (OR) and 95% confidence intervals (CI) for diabetes risk according to MDS.
RESULTS: After adjusting for sociodemographic factors, family history of diabetes, and health behaviors, the OR (95% CI) for diabetes risk across quintiles of the MDS was 1.00 (reference) for Q1, 1.16 (0.77, 1.73) for Q2, 1.30 (0.88, 1.91) for Q3, 1.99 (1.36, 2.92) for Q4, and 2.47 (1.66, 3.67) for Q5. Each SD increase in MDS was associated with 36% higher diabetes risk (95% CI: 1.21, 1.54; P-trend <.0001). This association was moderately attenuated after additional adjustment for body mass index (comparable OR: 1.17; 95% CI: 1.02, 1.35; P-trend = .02). The MDS explained 17.6% of the association between self-reported psychological distress (defined as presence of depression or anxiety symptoms) and diabetes risk (P = .04).
CONCLUSIONS: MDS was significantly associated with diabetes risk in women. These results suggest that differences in multiple lipid and amino acid metabolites may underlie the observed association between psychological distress and diabetes risk.
OBJECTIVE: To evaluate the association between a metabolomic signature for psychological distress and diabetes risk.
METHODS: We conducted a nested case-control study of plasma metabolomics and diabetes risk in the Nurses\' Health Study, including 728 women (mean age: 55.2 years) with incident diabetes and 728 matched controls. Blood samples were collected between 1989 and 1990 and incident diabetes was diagnosed between 1992 and 2008. Based on our prior work, we calculated a weighted plasma metabolite-based distress score (MDS) comprised of 19 metabolites. We used conditional logistic regression accounting for matching factors and other diabetes risk factors to estimate odds ratios (OR) and 95% confidence intervals (CI) for diabetes risk according to MDS.
RESULTS: After adjusting for sociodemographic factors, family history of diabetes, and health behaviors, the OR (95% CI) for diabetes risk across quintiles of the MDS was 1.00 (reference) for Q1, 1.16 (0.77, 1.73) for Q2, 1.30 (0.88, 1.91) for Q3, 1.99 (1.36, 2.92) for Q4, and 2.47 (1.66, 3.67) for Q5. Each SD increase in MDS was associated with 36% higher diabetes risk (95% CI: 1.21, 1.54; P-trend <.0001). This association was moderately attenuated after additional adjustment for body mass index (comparable OR: 1.17; 95% CI: 1.02, 1.35; P-trend = .02). The MDS explained 17.6% of the association between self-reported psychological distress (defined as presence of depression or anxiety symptoms) and diabetes risk (P = .04).
CONCLUSIONS: MDS was significantly associated with diabetes risk in women. These results suggest that differences in multiple lipid and amino acid metabolites may underlie the observed association between psychological distress and diabetes risk.
摘要：
背景：心理困扰与糖尿病风险有关。很少以人口为基础，流行病学研究已经调查了潜在的分子机制(例如，代谢失调）潜在的这种关联。
目的：评估心理困扰的代谢组学特征与糖尿病风险之间的关联。
方法：我们在护士健康研究中进行了血浆代谢组学和糖尿病风险的巢式病例对照研究，包括728名女性(平均年龄:55.2岁)和728名匹配的对照组。在1989年至1990年之间收集血液样本，并在1992年至2008年之间诊断出糖尿病。根据我们之前的工作,我们计算了由19种代谢物组成的基于血浆代谢物的加权窘迫评分(MDS).我们使用条件逻辑回归，考虑匹配因素和其他糖尿病危险因素，根据MDS估计糖尿病风险的比值比（OR）和95％置信区间（CI）。
结果：在调整社会人口因素后，糖尿病家族史,和健康行为，在MDS的5个百分点中,Q1的糖尿病风险OR(95%CI)为1.00(参考),Q2为1.16(0.77,1.73),Q3为1.30(0.88,1.91),Q4为1.99(1.36,2.92),Q5为2.47(1.66,3.67).MDS的SD增加与36％的糖尿病风险增加相关（95％CI：1.21，1.54；P趋势<0.0001）。在进一步调整体重指数后，这种关联中度减弱（可比OR：1.17；95％CI：1.02，1.35；P趋势=.02）。MDS解释了17.6％的自我报告的心理困扰（定义为存在抑郁或焦虑症状）与糖尿病风险之间的关联（P=0.04）。
结论：MDS与女性糖尿病风险显著相关。这些结果表明，多种脂质和氨基酸代谢产物的差异可能是心理困扰与糖尿病风险之间观察到的关联的基础。
目的：评估心理困扰的代谢组学特征与糖尿病风险之间的关联。
方法：我们在护士健康研究中进行了血浆代谢组学和糖尿病风险的巢式病例对照研究，包括728名女性(平均年龄:55.2岁)和728名匹配的对照组。在1989年至1990年之间收集血液样本，并在1992年至2008年之间诊断出糖尿病。根据我们之前的工作,我们计算了由19种代谢物组成的基于血浆代谢物的加权窘迫评分(MDS).我们使用条件逻辑回归，考虑匹配因素和其他糖尿病危险因素，根据MDS估计糖尿病风险的比值比（OR）和95％置信区间（CI）。
结果：在调整社会人口因素后，糖尿病家族史,和健康行为，在MDS的5个百分点中,Q1的糖尿病风险OR(95%CI)为1.00(参考),Q2为1.16(0.77,1.73),Q3为1.30(0.88,1.91),Q4为1.99(1.36,2.92),Q5为2.47(1.66,3.67).MDS的SD增加与36％的糖尿病风险增加相关（95％CI：1.21，1.54；P趋势<0.0001）。在进一步调整体重指数后，这种关联中度减弱（可比OR：1.17；95％CI：1.02，1.35；P趋势=.02）。MDS解释了17.6％的自我报告的心理困扰（定义为存在抑郁或焦虑症状）与糖尿病风险之间的关联（P=0.04）。
结论：MDS与女性糖尿病风险显著相关。这些结果表明，多种脂质和氨基酸代谢产物的差异可能是心理困扰与糖尿病风险之间观察到的关联的基础。
