Table 6_Bright night sleeping environment induces diabetes and impaired glucose tolerance in non-human primates.docx

BackgroundAccording to the IDF Diabetes Atlas regularly published by International Diabetes Federation, the prevalence of diabetes and impaired glucose tolerance (IGT), diabetes-related mortality and health expenditure are becoming serious eventually at the global, regional and national level. While the data alarm people, the exact cause remains unknown. It is widely accepted that glucose metabolism can be impaired by circadian rhythms disruption and sleep disturbances, both closely linked to exposure to light at night. However, there is little direct experiment on primates to study the precise extent of how serious bright sleeping environment at night impairs glucose metabolism, what the relationship is between nocturnal brightness and the development of diabetes and IGT, any difference between male and female, and whether aging and weight are involved. This study aims to address these questions in monkeys.
MethodsIn a reduced daytime bright condition resembling human living rooms, 197 Cynomolgus (130 male, 67 female) were exposed to three distinct light intensities (13, 35, 75Lux) at night for consecutive ten months. Animals were retrospectively divided into four groups according to glucose metabolic status by the end of the experimental session, spontaneous diabetes mellitus (SDM, N=11), light-induced diabetes (LID, N=83), impaired fasting glucose tolerance (IFG, N=36), and normal glucose tolerance (NGT, N=67). Data pertaining to the glucose metabolism such as concentrations of fasting glucose, glycosylated hemoglobin, plasma insulin and C-peptide were collected monthly and analyzed.
Results1) Bright night exasperated glucose metabolism in individuals with pre-existing diabetes, led to premature death; 2) Stronger white light intensity-dependently induced diabetes and IFG in previous healthy monkeys: the brighter the light, the quicker the metabolism disturbance and IFG developed, and also the higher morbidity of LID and IFG; 3) Exposure to nocturnal light had a synergistic impairing effect on glucose metabolism with aging and weight. 4) Female were more susceptible to night brightness.
ConclusionsLight in sleeping environment exacerbates glucose metabolism in individuals with pre-existing diabetes, leads to IFG and diabetes in healthy primates. Moreover, the harmful effects of bright night on glucose metabolism are synergistic with aging and weight.

背景 据国际糖尿病联盟（International Diabetes Federation, IDF）定期发布的《糖尿病地图集》显示，在全球、区域及国家层面，糖尿病与糖耐量减低（impaired glucose tolerance, IGT）的患病率、糖尿病相关死亡率及卫生支出均日趋严峻。尽管此类数据警示世人，但糖尿病的确切病因仍未明确。目前学界普遍认为，昼夜节律紊乱与睡眠障碍可损伤葡萄糖代谢，而二者均与夜间光照暴露密切相关。然而，针对灵长类动物的直接实验极少，难以明确夜间明亮睡眠环境对葡萄糖代谢的损伤程度、夜间光照与糖尿病及IGT发生的关联、是否存在性别差异，以及年龄与体重是否参与致病过程。本研究旨在以食蟹猴为实验对象，解答上述问题。

方法 本研究设置了模拟人类起居室的弱日间光照环境，将197只食蟹猴（雄性130只、雌性67只）夜间暴露于三种不同光照强度（13、35、75勒克斯），持续时长为连续10个月。实验结束后，研究人员依据受试动物的葡萄糖代谢状态将其回顾性分为四组：自发性糖尿病（spontaneous diabetes mellitus, SDM，N=11）、光诱导糖尿病（light-induced diabetes, LID，N=83）、空腹糖耐量受损（impaired fasting glucose tolerance, IFG，N=36）及糖耐量正常（normal glucose tolerance, NGT，N=67）。研究人员每月采集空腹血糖、糖化血红蛋白、血浆胰岛素及C肽等与葡萄糖代谢相关的指标并进行分析。

结果 1. 夜间强光会加重已患糖尿病个体的葡萄糖代谢损伤，甚至导致过早死亡；2. 光照强度越高，健康食蟹猴越易诱发糖尿病与IFG：光照亮度越高，代谢紊乱及IFG出现得越快，光诱导糖尿病与IFG的发病率也越高；3. 夜间光照与年龄、体重对葡萄糖代谢损伤存在协同效应；4. 雌性个体对夜间光照的敏感性更高。

结论 睡眠环境中的光照会加重已患糖尿病个体的葡萄糖代谢损伤，并可使健康灵长类动物出现IFG与糖尿病。此外，夜间强光对葡萄糖代谢的损害作用与年龄、体重存在协同效应。