Department of Internal Medicine, Morehouse School of Medicine, Atlanta, GA, United States of America.
College of Nursing, Walden University, Minneapolis, MN, United States of America.
PLoS One. 2023 May 23;18(5):e0285827. doi: 10.1371/journal.pone.0285827. eCollection 2023.
Carbohydrate and protein dietary proportions have been debated as to whether higher or lower levels are optimal for diabetes metabolic control.
The objective of this study was to investigate the associations, interactions, and mediational relationships between a polygenic risk score (PRS), carbohydrate and protein intake, and physical activity level on type 2 diabetes (T2DM) by genetic ancestry, in European Americans and African Americans. A secondary objective examined the biological pathways associated with the PRS-linked genes and their relationships to dietary intake.
We performed a cross-sectional study in 9,393 participants: 83.3% European Americans and 16.7% African Americans from 7-NHLBI Care studies obtained from the database of Genotypes and Phenotypes. The main outcome was T2DM. Carbohydrate and protein intake derived from food frequency questionnaires were calculated as percent calories. Data were analyzed using multivariable generalized estimation equation models to derive odds ratios (OR) and 95% confidence intervals (CI). Ancestry-specific PRSs were constructed using joint-effects Summary Best Linear Unbiased Estimation in the train dataset and replicated in the test dataset. Mediation analysis was performed using VanderWeele's method.
The PRS in the highest tertile was associated with higher risk of T2DM in European Americans (OR = 1.25;CI = 1.03-1.51) and African Americans (OR = 1.54;1.14-2.09). High carbohydrate and low protein intake had lower risks of T2DM when combined with the PRS after adjusting for covariates. In African Americans, high physical activity combined with the high PRS and high protein diet was associated with a 28% lower incidence of T2DM when compared to low physical activity. In mediational models in African Americans, the PRS-T2DM association was mediated by protein intake in the highest tertile by 55%. The top PRS tertile had the highest magnitude of risks with metabolic factors that were significantly associated with T2DM, especially in European Americans. We found metabolic pathways associated with the PRS-linked genes that were related to insulin/IGF and ketogenesis/ketolysis that can be activated by moderate physical activity and intermittent fasting for better T2DM control.
Clinicians may want to consider diets with a higher portion of carbohydrates than protein, especially when the burden of high-risk alleles is great in patients with T2DM. In addition, clinicians and other medical professionals may want to emphasize the addition of physical activity as part of treatment regimen especially for African Americans. Given the metabolic pathways we identified, moderate physical activity and intermittent fasting should be explored. Researchers may want to consider longitudinal or randomized clinical trials to determine the predictive ability of different dietary patterns to inhibit T2DM in the presence of obesity and an elevated PRS.
关于碳水化合物和蛋白质的膳食比例，究竟哪种水平更高或更低对糖尿病代谢控制更有利，一直存在争议。
本研究旨在通过遗传血统，调查多基因风险评分（PRS）、碳水化合物和蛋白质摄入量以及体力活动水平与 2 型糖尿病（T2DM）之间的关联、相互作用和中介关系，对象为欧洲裔美国人和非裔美国人。次要目标是研究与 PRS 相关基因相关的生物学途径及其与饮食摄入的关系。
我们对来自 7 个 NHLBI 护理研究的数据库中的 9393 名参与者进行了一项横断面研究：83.3%为欧洲裔美国人，16.7%为非裔美国人。主要结局是 T2DM。通过食物频率问卷计算碳水化合物和蛋白质的摄入量，作为卡路里的百分比。使用多变量广义估计方程模型分析数据，得出比值比（OR）和 95%置信区间（CI）。在训练数据集中使用联合效应最佳线性无偏估计构建了特定于血统的 PRS，并在测试数据集中进行了复制。使用 VanderWeele 方法进行中介分析。
在欧洲裔美国人（OR=1.25；95%CI=1.03-1.51）和非裔美国人（OR=1.54；1.14-2.09）中，PRS 处于最高三分位与 T2DM 的风险增加相关。在调整了协变量后，高碳水化合物和低蛋白质饮食与 PRS 结合可降低 T2DM 的风险。在非裔美国人中，与低体力活动相比，高体力活动与高 PRS 和高蛋白饮食相结合与 T2DM 发病率降低 28%相关。在非裔美国人的中介模型中，PRST2DM 关联通过最高三分位的蛋白质摄入量介导了 55%。PRS 最高三分位与代谢因素的关联程度最大，这些因素与 T2DM 显著相关，尤其是在欧洲裔美国人中。我们发现与 PRS 相关基因相关的代谢途径与胰岛素/IGF 和酮生成/酮解有关，适度的体力活动和间歇性禁食可以激活这些途径，从而更好地控制 T2DM。
临床医生可能需要考虑饮食中碳水化合物的比例高于蛋白质，特别是在 T2DM 患者的高风险等位基因负担较大的情况下。此外，临床医生和其他医疗保健专业人员可能希望强调将体力活动作为治疗方案的一部分，尤其是对于非裔美国人。鉴于我们确定的代谢途径，应探索适度的体力活动和间歇性禁食。研究人员可能希望考虑进行纵向或随机临床试验，以确定不同饮食模式在肥胖和升高的 PRS 存在下抑制 T2DM 的预测能力。
