Poor Sleep Quality Is Associated with Dawn Phenomenon and Impaired Circadian Clock Gene Expression in Subjects with Type 2 Diabetes Mellitus

Aims. We investigated whether poor sleep quality is associated with both dawn phenomenon and impaired circadian clock gene expression in subjects with diabetes. Methods. 81 subjects with diabetes on continuous glucose monitoring were divided into two groups according to the Pittsburgh Sleep Quality Index. The magnitude of dawn phenomenon was quantified by its increment from nocturnal nadir to prebreakfast. Peripheral leucocytes were sampled from 81 subjects with diabetes and 28 normal controls at 09:00. Transcript levels of circadian clock genes (BMAL1, PER1, PER2, and PER3) were determined by real-time quantitative polymerase chain reaction. Results. The levels of HbA1c and fasting glucose and the magnitude of dawn phenomenon were significantly higher in the diabetes group with poor sleep quality than that with good sleep quality. Peripheral leucocytes from subjects with poor sleep quality expressed significantly lower transcript levels of BMAL1 and PER1 compared with those with good sleep quality. Poor sleep quality was significantly correlated with magnitude of dawn phenomenon. Multiple linear regression showed that sleep quality and PER1 were significantly independently correlated with dawn phenomenon. Conclusions. Dawn phenomenon is associated with sleep quality. Furthermore, mRNA expression of circadian clock genes is dampened in peripheral leucocytes of subjects with poor sleep quality.

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Differential Expression of Circadian Clock Genes in the Bovine Neuroendocrine Adrenal System

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.134 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A66-A67

Author(s):

Audrey L Earnhardt ◽

David G Riley ◽

Noushin Ghaffari ◽

Penny K Riggs ◽

Charles R Long ◽

...

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Clock Gene ◽

Target Genes ◽

Clock Genes ◽

Expression Profiles ◽

Primary Objective ◽

Clock Gene Expression ◽

Adrenal System ◽

Circadian Clock Genes

Abstract The primary objective of this investigation was to determine whether circadian clock genes were differentially expressed within or among bovine hypothalamic paraventricular nucleus (PVN), anterior pituitary gland (AP), adrenocortical (AC) and adrenomedullary (AM) tissues. The PVN, AP, AC, and AM were isolated from 5-yr-old Brahman cows (n = 8) harvested humanely at an abattoir between 0800-1100 h. Expression of target genes in each sample was evaluated via RNA-sequencing analyses. Gene counts were normalized using the trimmed mean of M values (TMM) method in the edgeR Package from Bioconductor, R. The normalized gene counts of genes important for circadian rhythm were statistically analyzed using the GLM Procedure of SAS. The genes analyzed were circadian locomotor output cycles protein kaput (CLOCK), cryptochrome circadian regulator 1 and 2 (CRY1 and CRY2), aryl hydrocarbon receptor nuclear translocator like (ARNTL), period circadian regulator 1 and 2 (PER1 and PER2), neuronal PAS domain protein 2 (NPAS2), and nuclear receptor subfamily 1 group D member 1 (NR1D1). Overall, relative expression profiles of clock genes differed (P < 0.01) within each tissue with PER1 having greater expression in all tissues (P < 0.01). Within the PVN expression of CLOCK, CRY1, ARNTL, and PER2 was less than that of CRY2, NPAS2, and NR1D1 (P < 0.01). In the AP, with the exception of PER1, no other clock gene differed in degree of expression. In the AC, expression of CLOCK and NPAS2 was greater than CRY1, ARNTL, PER2, and NR1D1 (P < 0.05), whereas CRY2 expression exceeded only CRY1 (P < 0.05). Within the AM, CLOCK and CRY2 expression was greater than CRY1 and ARNTL (P < 0.05). Overall, clock gene expression among tissues differed (P < 0.01) for each individual clock gene. The AC and AM had similar clock gene expression, except expression of CRY2 and PER2 was greater in AM (P < 0.05). The AC and AM had greater expression of CLOCK than the PVN and AP (P < 0.01), with PVN having greater expression than AP (P < 0.01). The AP had greater expression of NPAS2, followed by PVN, with the least expression in the AC and AM (P < 0.01). Both PVN and AP had greater CRY1 and NR1D1 expression than AC or AM (P < 0.01). The AP had greater PER1 expression than PVN, AC, and AM (P < 0.01), whereas PVN, AC, and AM had greater ARNTL expression than AP (P < 0.05). Both AP and AM had greater expression of PER2 than PVN or AC (P < 0.01). The PVN had greater expression of CRY2 than the AP, AC, and AM (P < 0.01). These results indicated that within each tissue the various clock genes were expressed in different quantities. Also, the clock genes were expressed differentially among the tissues of the bovine neuroendocrine adrenal system. Temporal relationships of these genes with the primary endocrine products of these tissues should be investigated to define the roles of peripheral clock genes in regulation of metabolism and health.

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Association of Circadian Clock Gene Expression with Glioma Tumor Microenvironment and Patient Survival

Cancers ◽

10.3390/cancers13112756 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2756

Author(s):

Julianie De La Cruz Minyety ◽

Dorela D. Shuboni-Mulligan ◽

Nicole Briceno ◽

Demarrius Young ◽

Mark R. Gilbert ◽

...

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Clock Gene ◽

Clock Genes ◽

The Cancer Genome Atlas ◽

Lower Grade ◽

Circadian Clock Gene ◽

Clock Gene Expression ◽

Mutational Status ◽

Circadian Clock Genes

Circadian clock genes have been linked to clinical outcomes in cancer, including gliomas. However, these studies have not accounted for established markers that predict the prognosis, including mutations in Isocitrate Dehydrogenase (IDH), which characterize the majority of lower-grade gliomas and secondary high-grade gliomas. To demonstrate the connection between circadian clock genes and glioma outcomes while accounting for the IDH mutational status, we analyzed multiple publicly available gene expression datasets. The unsupervised clustering of 13 clock gene transcriptomic signatures from The Cancer Genome Atlas showed distinct molecular subtypes representing different disease states and showed the differential prognosis of these groups by a Kaplan–Meier analysis. Further analyses of these groups showed that a low period (PER) gene expression was associated with the negative prognosis and enrichment of the immune signaling pathways. These findings prompted the exploration of the relationship between the microenvironment and clock genes in additional datasets. Circadian clock gene expression was found to be differentially expressed across the anatomical tumor location and cell type. Thus, the circadian clock expression is a potential predictive biomarker in glioma, and further mechanistic studies to elucidate the connections between the circadian clock and microenvironment are warranted.

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TAMI-44. ASSOCIATION OF CIRCADIAN CLOCK GENE EXPRESSION WITH GLIOMA TUMOR MICROENVIRONMENT AND PATIENT SURVIVAL

Neuro-Oncology ◽

10.1093/neuonc/noab196.827 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi207-vi207

Author(s):

Julianie De La Cruz Minyety ◽

Dorela Shuboni-Mulligan ◽

Nicole Briceno ◽

Demarrius Young Jr. ◽

Mark Gilbert ◽

...

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Clock Gene ◽

Clock Genes ◽

Cell Types ◽

The Cancer Genome Atlas ◽

Wild Type ◽

Clock Gene Expression ◽

Mutational Status ◽

Circadian Clock Genes

Abstract Circadian clock genes have been linked to differences in clinical outcomes in cancer, including gliomas. However, these studies have not accounted for established prognostic markers, including mutations in Isocitrate Dehydrogenase (IDH). To study the connection between circadian clock genes and glioma outcomes while accounting for IDH mutational status, we analyzed multiple publicly available gene expression datasets. Unsupervised clustering of 13 clock gene transcriptomic signatures from The Cancer Genome Atlas resulted in four distinct transcriptomic clusters, two clusters were enriched for IDH mutant (Circadian 1-2) and the others for IDH wild-type gliomas (Circadian 3-4). Within these clusters we observed differential prognosis of the patients by Kaplan–Meier analysis (Circadian 1-2, p=0.0001; Circadian 3-4, p=0.0002) suggesting that these transcriptomic circadian subtypes might reflect different disease states. Further analyses using Cox Proportional Hazards Regression showed that lower Period (PER) gene expression was associated with worse prognosis (increasing PER expression HR=0.655, p=0.007) independent of IDH wild-type status (HR=5.312, p< 0.001) and increasing age (HR = 1.04, p< 0.001). Lower PER expression was associated with enrichment of a number of immune signaling pathways. These findings prompted the exploration of the relationship between microenvironment and clock genes using the Ivy GAP dataset to explore tumor location-specific differences and single cell RNA sequencing data from Darmanis (accession: GSE84465) to explore cell-specific differences. Circadian clock genes were found to be differentially expressed across anatomical tumor locations and cell types, including microglia. In ongoing studies we are examining the role of the microenvironment and PER2 expression on tumor growth by disrupting PER2 expression in tumor cells and microglia using IDH mutant and wild-type in vitro models. Clock gene expression is a potential prognostic biomarker in glioma and further studies to elucidate the importance of circadian rhythms in other cell types beyond the tumor are warranted.

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Relationshp Between Sleep Quality, Mood State, and Performance of Elite Air-Rifle Shooters

10.21203/rs.3.rs-1145112/v1 ◽

2021 ◽

Author(s):

Jiaojiao Lu ◽

Yan An ◽

Jun Qiu

Keyword(s):

Sleep Quality ◽

Mood State ◽

Sleep Latency ◽

Sleep Time ◽

Poor Sleep ◽

Poor Sleep Quality ◽

Somatic Anxiety ◽

And Performance ◽

Air Rifle ◽

Good Sleep

Abstract Background To evaluate the impact of pre-competition sleep quality on the mood and performance of elite air-rifle shooters. Methods This study included 23 elite air-rifle shooters who participated in an air-rifle shooting-competition from April 2019 to October 2019. Sleep time, sleep efficiency, sleep latency, and wake-up time after sleep onset were monitored using actigraphy. The Pittsburgh sleep quality index and Profile of Mood State were used to assess sleep quality. Competitive State Anxiety Inventory-2 was used to evaluate mood state. Results The average time to fall asleep, sleep time, sleep efficiency, and subjective sleep quality were 20.6 ± 14.9 min, 7.0 ± 0.8 h, 85.9 ± 5.3%, and 5.2 ± 2.2, respectively. Sleep quality decreased as the competition progressed. Pre-competition sleep time in female athletes was significantly higher than that on the competition day (P = 0.05). Pre-competition sleep latency was significantly longer in women than in men (P = 0.021). During training and pre-competition, the tension, fatigue, depression, and emotional disturbance were significantly lower in athletes with good sleep quality than in athletes with poor sleep quality. Athletes with good sleep quality had significantly more energy. The PSQI total score was positively correlated with positive emotion, TMD, cognitive anxiety, and somatic anxiety POMS scores, and negatively correlated with energy and self-confidence scores. Race scores and depression and somatic anxiety scores were negatively correlated. Conclusion Poor sleep quality negatively impacted the mood of athletes; however, sleep indices and competition performance of athletes during competitions were not significantly correlated.

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The Molecular Evolution of Circadian Clock Genes in Spotted Gar (Lepisosteus oculatus)

Genes ◽

10.3390/genes10080622 ◽

2019 ◽

Vol 10 (8) ◽

pp. 622 ◽

Cited By ~ 2

Author(s):

Yi Sun ◽

Chao Liu ◽

Moli Huang ◽

Jian Huang ◽

Changhong Liu ◽

...

Keyword(s):

Circadian Clock ◽

Teleost Fish ◽

Clock Gene ◽

Genome Duplication ◽

Clock Genes ◽

Gene Families ◽

Regulatory Mechanisms ◽

Spotted Gar ◽

Circadian Clock Genes ◽

Lepisosteus Oculatus

Circadian rhythms are biological rhythms with a period of approximately 24 h. While canonical circadian clock genes and their regulatory mechanisms appear highly conserved, the evolution of clock gene families is still unclear due to several rounds of whole genome duplication in vertebrates. The spotted gar (Lepisosteus oculatus), as a non-teleost ray-finned fish, represents a fish lineage that diverged before the teleost genome duplication (TGD), providing an outgroup for exploring the evolutionary mechanisms of circadian clocks after whole-genome duplication. In this study, we interrogated the spotted gar draft genome sequences and found that spotted gar contains 26 circadian clock genes from 11 families. Phylogenetic analysis showed that 9 of these 11 spotted gar circadian clock gene families have the same number of genes as humans, while the members of the nfil3 and cry families are different between spotted gar and humans. Using phylogenetic and syntenic analyses, we found that nfil3-1 is conserved in vertebrates, while nfil3-2 and nfil3-3 are maintained in spotted gar, teleost fish, amphibians, and reptiles, but not in mammals. Following the two-round vertebrate genome duplication (VGD), spotted gar retained cry1a, cry1b, and cry2, and cry3 is retained in spotted gar, teleost fish, turtles, and birds, but not in mammals. We hypothesize that duplication of core clock genes, such as (nfil3 and cry), likely facilitated diversification of circadian regulatory mechanisms in teleost fish. We also found that the transcription factor binding element (Ahr::Arnt) is retained only in one of the per1 or per2 duplicated paralogs derived from the TGD in the teleost fish, implicating possible subfuctionalization cases. Together, these findings help decipher the repertoires of the spotted gar’s circadian system and shed light on how the vertebrate circadian clock systems have evolved.

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Cognitive impairment as a function of sleep quality and gender

Journal of Biomedical Sciences ◽

10.3126/jbs.v6i3.26822 ◽

2019 ◽

pp. 4

Author(s):

R. Akhil ◽

B.P. Nair

Keyword(s):

Working Memory ◽

Reaction Time ◽

Sleep Quality ◽

Sustained Attention ◽

Divided Attention ◽

Poor Sleep ◽

Poor Sleep Quality ◽

Vigilance Test ◽

And Gender ◽

Good Sleep

Background: The study aims at finding whether there is any significant difference between sub-groups classified on the basis of sleep quality (good sleep quality and poor sleep quality) and gender in the performance of various cognitive functioning tests like Visual N Back Test (N Back 1and N Back 2 test) for working memory, Triad test for divided attention, Digit Vigilance Test for sustained attention and Reaction time test (simple reaction time and choice reaction time). Materials and methods: The sample consisted of 30 participants, both males (N=13) and females (N=17) in the age range between 18 to 30 years, randomly drawn from Thiruvananthapuram and Kollam districts of Kerala. The participants of the study are screened and categorized into two groups of 15 members each on the basis of the scores obtained in the Pittsburgh Sleep Quality Index (PSQI). t-test and two-way ANOVA were performed to test the significance of the hypotheses. Results: The results showed that the participants with poor sleep quality significantly differed from those with good sleep quality and committed more number of errors in the triad test of divided attention and took more time and committed more errors in the completion of the digit vigilance test of sustained attention. Conclusion: A gender advantage favoring females was seen on the test of working memory, test for sustained attention and the test for choice reaction time. An interaction between sleep quality and gender was noticed only on the test of divided attention. It was seen that males with poor sleep quality are more impaired in divided attention tasks than females with poor sleep quality.

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MON-698 Association of Sleep Quality and Painless Diabetic Peripheral Neuropathy in Type 2 Diabetes

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.882 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Dughyun Choi ◽

Bo Yeon Kim ◽

Chan-Hee Jung ◽

Chul-Hee Kim ◽

Jioh Mok

Keyword(s):

Type 2 Diabetes ◽

Peripheral Neuropathy ◽

Sleep Quality ◽

Diabetic Peripheral Neuropathy ◽

Poor Sleep ◽

Poor Sleep Quality ◽

The Poor ◽

Painful Sensation ◽

Good Sleep

Abstract Aims Diabetic peripheral neuropathy (DPN) is one of the most common and early manifested complication in T2D. Previous reports have shown that painful sensation of diabetic peripheral neuropathy (DPN) results in sleep problems in type 2 diabetes (T2D)1, 2. However, it is not known that subtype of DPN, the painless DPN also is associated with poor sleep quality in T2D. The purpose of the current study was to investigate the association between painless DPN and poor sleep quality in T2D. Methods A total of 146 patients of T2D who did not previously diagnose with symptomatic DPN were recruited into the study. Among the patients, painless DPN was diagnosed by using the current perception threshold (CPT) test. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Results The percentage of painless DPN was significantly higher in the poor sleep quality group than the good sleep quality group (70.0% vs. 35.5%, P<0.001). In the subscale results, stimulus values in 2000 Hz, hypoesthesia and hyperesthesia were significantly higher in the poor sleep quality group, than in the good sleep quality group (45.7% vs. 25.0%, P=0.009; 34.3% vs. 18.4%, P=0.029; 40.0% vs. 19.7%, P=0.007, respectively). The association of painless DPN and poor sleep quality remained significant after adjustment for significant variants (odds ratio, 3.825; 95% confidence interval, 1.674-8.742; P<0.001). Conclusions The current study showed that painless DPN was associated with poor sleep quality. Future studies are required to clarify the pathophysiologic causal relationship between painless DPN and sleep quality. References 1. Gore M, Brandenburg NA, Dukes E, Hoffman DL, Tai K-S, Stacey B. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. Journal of pain and symptom management. 2005;30(4): 374-385. 2. Zelman DC, Brandenburg NA, Gore M. Sleep impairment in patients with painful diabetic peripheral neuropathy. Clin J Pain. 2006;22(8): 681-685.

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Decrease in Sleep Duration and Poor Sleep Quality over Time Is Associated with an Increased Risk of Incident Non-Alcoholic Fatty Liver Disease

Journal of Personalized Medicine ◽

10.3390/jpm12010092 ◽

2022 ◽

Vol 12 (1) ◽

pp. 92

Author(s):

Yoo Jin Um ◽

Yoosoo Chang ◽

Hyun-Suk Jung ◽

In Young Cho ◽

Jun Ho Shin ◽

...

Keyword(s):

Sleep Quality ◽

Sleep Duration ◽

Poor Sleep ◽

Poor Sleep Quality ◽

Alcoholic Fatty Liver ◽

Increased Risk ◽

Alcoholic Fatty Liver Disease ◽

Good Sleep ◽

Over Time

The impact of changes in sleep duration and sleep quality over time on the risk of non-alcoholic fatty liver disease (NAFLD) is not known. We investigated whether changes in sleep duration and in sleep quality between baseline and follow-up are associated with the risk of developing incident NAFLD. The cohort study included 86,530 Korean adults without NAFLD and with a low fibrosis score at baseline. The median follow-up was 3.6 years. Sleep duration and quality were assessed using the Pittsburgh Sleep Quality Index. Hepatic steatosis (HS) and liver fibrosis were assessed using ultrasonography and the fibrosis-4 index (FIB-4). Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (Cis). A total of 12,127 subjects with incident HS and 559 with incident HS plus intermediate/high FIB-4 was identified. Comparing the decrease in sleep duration of >1 h, with stable sleep duration, the multivariate-adjusted HR (95% CIs) for incident HS was 1.24 (1.15–1.35). The corresponding HRs for incident HS plus intermediate/high FIB-4 was 1.58 (1.10–2.29). Comparing persistently poor sleep quality with persistently good sleep quality, the multivariate-adjusted HR for incident HS was 1.13 (95% CI, 1.05–1.20). A decrease in sleep duration or poor sleep quality over time was associated with an increased risk of incident NAFLD, underscoring an important potential role for good sleep in preventing NAFLD risk.

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Quality of sleep and use of computers and cell-phones among university students

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.65.12.1454 ◽

2019 ◽

Vol 65 (12) ◽

pp. 1454-1458 ◽

Cited By ~ 1

Author(s):

Diogo von Gaevernitz Lima ◽

Ana Claudia Garabeli Cavalli Kluthcovsky ◽

Luiz Gustavo Rachid Fernandes ◽

Giovane Okarenski

Keyword(s):

Medical Students ◽

Sleep Quality ◽

Computer Use ◽

Cell Phones ◽

Poor Sleep ◽

Quality Of Sleep ◽

Poor Sleep Quality ◽

Cross Sectional ◽

Good Sleep

SUMMARY OBJECTIVE Evaluate the quality of sleep and its association with the use of computers and cell-phones among medicine and dentistry students. METHODS Cross-sectional and comparative study, which evaluated 425 students through a socioeconomic questionnaire, the Pittsburgh Sleep Quality Index(PSQI), and a questionnaire on their use of computers and cell phones. RESULTS Poor sleep quality was observed in 61.4% of medical students and in 60.1% of dentistry students. Medical students with poor sleep quality had a higher mean time of computer use at night when compared to those with good sleep quality (p=0.04), as well as for computer (p<0.001) and cell phone use (p<0.01) immediately before bedtime. Dentistry students with poor sleep quality had a higher average time of computer use before bedtime than those with good sleep quality (p=0.03). CONCLUSION Students should receive guidance on prevention strategies and quality of sleep care.

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Influence of obesity, weight loss, and free fatty acids on skeletal muscle clock gene expression

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00289.2019 ◽

2020 ◽

Vol 318 (1) ◽

pp. E1-E10 ◽

Cited By ~ 3

Author(s):

Laura Sardon Puig ◽

Nicolas J. Pillon ◽

Erik Näslund ◽

Anna Krook ◽

Juleen R. Zierath

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Weight Loss ◽

Circadian Clock ◽

Clock Gene ◽

Clock Genes ◽

Expression Profiles ◽

Normal Weight ◽

Nonesterified Fatty Acid ◽

Clock Gene Expression

The molecular circadian clock plays a role in metabolic homeostasis. We tested the hypothesis obesity and systemic factors associated with insulin resistance affect skeletal muscle clock gene expression. We determined clock gene expression in skeletal muscle of obese women ( n = 5) and men ( n = 18) before and 6 mo after Roux-en-Y gastric bypass (RYGB) surgery and normal-weight controls (women n = 6, men n = 8). Skeletal muscle clock gene expression was affected by obesity and weight loss. CRY1 mRNA ( P = 0.05) was increased and DBP mRNA ( P < 0.05) was decreased in obese vs. normal weight women and restored to control levels after RYGB-induced weight loss. CLOCK, CRY1, CRY2, and DBP mRNA ( P < 0.05) was decreased in obese men compared with normal weight men. Expression of all other clock genes was unaltered by obesity or weight loss in both cohorts. We correlated clock gene expression with clinical characteristics of the participants. Among the genes studied, DBP and PER3 expression was inversely correlated with plasma lipids in both cohorts. Circadian time-course studies revealed that core clock genes oscillate over time ( P < 0.05), with BMAL1, CIART, CRY2, DBP, PER1, and PER3 expression profiles altered by palmitate treatment. In conclusion, skeletal muscle clock gene expression and function is altered by obesity, coincident with changes in plasma lipid levels. Palmitate exposure disrupts clock gene expression in myotubes, indicating that dyslipidemia directly alters the circadian program. Strategies to reduce lipid overload and prevent elevations in nonesterified fatty acid and cholesterol levels may sustain circadian clock signals in skeletal muscle.

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