Department of Internal Medicine, Health Science Center, Ningbo University, Ningbo, Zhejiang, P. R. China.
School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, P. R. China.
Ann Med. 2023 Dec;55(1):1262-1286. doi: 10.1080/07853890.2023.2191218.
Disturbed circadian rhythms have been a risk factor for type 2 diabetes mellitus (T2DM). Melatonin is the major chronobiotic hormone regulating both circadian rhythm and glucose homeostasis. The rs10830963 (G allele) of the () gene has the strongest genetic associations with T2DM according to several genome-wide association studies. The rs10830963 G allele is also associated with disturbed circadian phenotypes and altered melatonin secretion, both factors that can elevate the risk of diabetes. Furthermore, evolutionary studies implied the presence of selection pressure and ethnic diversity in , which was consistent with the "thrifty gene" hypothesis in T2DM. The rs10830963 G risk allele is associated with delayed melatonin secretion onset in dim-light and prolonged duration of peak melatonin. This delayed melatonin secretion may help human ancestors adapt to famine or food shortages during long nights and early mornings and avoid nocturnal hypoglycemia but confers susceptibility to T2DM due to adequate energy intake in modern society. We provide new insight into the role of variants in T2DM disturbed circadian rhythms from the perspective of the "thrifty gene" hypothesis; these data indicate a novel target for the prevention and treatment of susceptible populations with the thrifty genotype.
昼夜节律紊乱已成为 2 型糖尿病（T2DM）的一个风险因素。褪黑素是调节昼夜节律和葡萄糖稳态的主要生物钟激素。根据几项全基因组关联研究，（）基因的 rs10830963（G 等位基因）与 T2DM 的遗传相关性最强。该 rs10830963 G 等位基因还与昼夜节律表型紊乱和褪黑素分泌改变有关，这两个因素都可能增加糖尿病的风险。此外，进化研究表明，在 中存在选择压力和种族多样性，这与 T2DM 中的“节俭基因”假说一致。rs10830963 G 风险等位基因与暗光下褪黑素分泌起始延迟和褪黑素峰值持续时间延长有关。这种褪黑素分泌延迟可能有助于人类祖先在长夜和清晨适应饥荒或食物短缺，避免夜间低血糖，但由于现代社会摄入足够的能量，使人类易患 T2DM。我们从“节俭基因”假说的角度提供了（）变体在 T2DM 中导致昼夜节律紊乱的新见解；这些数据表明，对于具有节俭基因型的易感人群，预防和治疗提供了一个新的目标。
