Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Nutr Metab Cardiovasc Dis. 2019 Nov;29(11):1176-1184. doi: 10.1016/j.numecd.2019.06.020. Epub 2019 Jun 28.
Preference for activity in the morning or evening (chronotype) may impact type 2 diabetes (T2D) risk factors. Our objective was to use Mendelian randomization (MR) to evaluate whether there are causal links between chronotype and one potential T2D risk factor, total fatty acids (TOTFA), and between TOTFA and T2D.
We estimated the causal effect of: 1) morning chronotype on TOTFA; and 2) higher TOTFA on T2D. We found that: a) morning compared to evening chronotype was associated with lower TOTFA levels (inverse-weighted variance (IVW) estimate -0.21; 95% CI -0.38, -0.03; raw P = 0.02; FDR-corrected P 0.04) and b) elevated TOTFA levels were protective against T2D (IVW estimate -0.23; 95% CI -0.41, -0.05; raw P = 0.01; FDR-corrected P = 0.03). Based on this finding, we further hypothesized that healthy fats would show a similar pattern and performed MR of a) morning chronotype on omega-3 (Omega-3), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids; and b) MR of each of these fat types on T2D. We observed the same mediating-type pattern for chronotype, MUFA, and T2D as we had for chronotype, TOTFA, and T2D, and morning chronotype was associated with lower Omega-3.
Our findings provide suggestive, new information about relationships among chronotype, TOTFA, and T2D and about chronotype as a factor influencing Omega-3, MUFA, and TOTFA levels. In addition, we validated previous knowledge about MUFA and T2D. Morning chronotypes may predispose towards lower levels of TOTFA and some healthy fats, whereas higher levels of TOTFA and MUFA may protect against T2D.
在早上或晚上活动的偏好（生物钟类型）可能会影响 2 型糖尿病（T2D）的风险因素。我们的目的是使用孟德尔随机化（MR）来评估生物钟类型与 T2D 的一个潜在风险因素，即总脂肪酸（TOTFA）之间，以及 TOTFA 与 T2D 之间是否存在因果关系。
我们估计了以下两个因果效应：1）早晨生物钟类型对 TOTFA 的影响；2）更高的 TOTFA 对 T2D 的影响。我们发现：a）与夜间生物钟类型相比，早晨生物钟类型与较低的 TOTFA 水平相关（逆加权方差（IVW）估计值为-0.21；95%置信区间为-0.38，-0.03；原始 P 值为 0.02；经 FDR 校正的 P 值为 0.04），b）升高的 TOTFA 水平可预防 T2D（IVW 估计值为-0.23；95%置信区间为-0.41，-0.05；原始 P 值为 0.01；经 FDR 校正的 P 值为 0.03）。基于这一发现，我们进一步假设健康脂肪也会呈现出类似的模式，并进行了以下 MR 分析：a）早晨生物钟类型对欧米伽 3（Omega-3）、单不饱和脂肪酸（MUFA）和多不饱和脂肪酸（PUFA）的影响；b）每种脂肪类型对 T2D 的影响。我们观察到生物钟类型、MUFA 和 T2D 之间的中介类型模式与生物钟类型、TOTFA 和 T2D 之间的模式相同，并且早晨生物钟类型与 Omega-3 水平较低有关。
我们的研究结果提供了关于生物钟类型、TOTFA 和 T2D 之间关系的新信息，以及生物钟类型作为影响 Omega-3、MUFA 和 TOTFA 水平的因素的新信息。此外，我们验证了先前关于 MUFA 和 T2D 的知识。早晨生物钟类型可能导致 TOTFA 和某些健康脂肪水平降低，而较高的 TOTFA 和 MUFA 水平可能预防 T2D。
