| Objective To analyze the relationships between sleep characteristics and type 2diabetes mellitus(T2DM),screen and verify the differential expression of long non-codingRNA(lncRNA)in peripheral blood leukocytes of T2 DM patients and control group,construct an epigenetic risk score for T2 DM,analyze of the impact of epigenetic risk score and sleep characteristics of T2 DM and their potential interactions.It may provide scientific basis for the prevention and treatment strategies of T2 DM and the study of epigenetic mechanism.Method(1)The hospital-based case-control study was applied.From December 2018 to February 2020,totally 1376 participants(316 T2 DM cases and 1061 controls)were collected at the First Affiliated Hospital of Fujian Medical University and the Affiliated Union Hospital and(Fuzhou,China).Biological and behavioral factors through questionnaire surveying and clinical data collection were conducted,including sleep status collected by the PSQI scale.The correction of sleep characteristics and T2 DM were explored by using the logistic regression model.The cut-off values of sleep characteristics determined by a restrictive cubic spline graph were drawn for classification,and the joint action of sleep and epigenetic factors were analyzed by cross-sectional analysis with logistic regression model.(2)The expression level of lncRNA in peripheral blood mononuclear cells from the case group(n=105)and control group(n=105)was detected by real-time fluorescence quantitative-polymerase chain reaction.Logistic regression model was used to investigate whether lncRNAs are independent risk factors for T2 DM and its diagnostic value was evaluated by ROC curve.The joint action of sleep factors and epigenetic factors were analyzed by cross-sectional analysis with logistic regression model.Result(1)Night sleep duration<7 hours(odds ratio(OR)=1.579,95% confidence interval(CI): 1.023～2.438),sleep efficiency <80%(OR=1.797,95% CI:1.147～2.815),sleep latency ≥60min(OR=2.069,95% CI:1.237～3.461)and napping duration >1hour(OR=1.738,95% CI:1.015～2.977)were the risk factors for the development of T2 DM.Compared with people who sleep for 7～8 hours at night and don’t take a nap,those who sleep less than 7 hours at night and have a nap of more than 1 hour a day(OR=3.058,95% CI:1.239～7.547)have a higher risk of developing type 2 diabetes.(2)The stratification-interaction analysis showed that there are interactive action between night sleep duration and gender,age,and overweight and obesity on the prevalence of T2DM(P<0.05).The risk of association between night sleep duration<7hours and T2 DM have more significant in the men(OR=1.953,95% CI :1.308～2.918),the age <65 years(OR=2.218,95% CI : 1.405～3.501),and the overweight and obesity(OR=1.917,95% CI:1.236～2.971).Sleep efficiency and overweight and obese have an interactive effect on the prevalence of T2DM(P<0.05).The significantly risk of association between sleep efficiency <80% and T2 DM is significant in the overweight and obese(OR=2.625,95% CI:1.484～4.645).There are no interaction between sleep latency and nap duration with gender,age,high blood pressure,overweight and obesity,and alcohol intake on the prevalence of T2DM(P>0.05).(3)The expression of lncRNA ENST00000607042,lncRNA TUG1 and lncRNA MALAT1 in peripheral blood leukocytes of the T2 DM case group were higher than the control group,and the difference was statistically significant(P<0.05).The expression was higher in T2 DM patients with lacking of sleep duration than diabetes alone.Further multivariate logistic regression analysis showed that the high expression of lncRNA ENST00000607042(OR=2.100,95% CI: 1.468～3.003),lncRNA TUG1(OR=1.429,95% CI: 1.132～1.803)and lncRNA MALAT1(OR=2.124,95% CI: 1.471～3.065)are risk factor for T2 DM.(4)Patients with high epigenetic risk scores and shorter sleep duration had a significantly higher risk of T2 DM.Conclusion(1)Short night sleep duration,poor sleep efficiency,longer sleep latency and napping duration will increase the risk of T2 DM,and the shorter night sleep duration and longer nap duration have a joint action in T2 DM.(2)Epigenetic regulation plays an important role in the occurrence and development of T2 DM.High expression of lncRNA ENST00000607042,lncRNA TUG1 and lncRNA MALAT1 are independent risk factors for T2 DM.(3)lncRNAs showed high expression levels in T2 DM case group and the expression was higher in T2 DM patients with lacking of sleep duration than diabetes alone and people with only lack of sleep duration.lncRNAs and sleep duration have a joint action in the prevalence of T2 DM. |
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