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Benedict, Christian, DocentORCID iD iconorcid.org/000-0002-8911-4068
Publications (10 of 90) Show all publications
Tan, X., van Egmond, L., Chapman, C. D., Cedernaes, J. & Benedict, C. (2018). Aiding sleep in type 2 diabetes: therapeutic considerations. The Lancet Diabetes and Endocrinology, 6(1), 60-68
Open this publication in new window or tab >>Aiding sleep in type 2 diabetes: therapeutic considerations
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2018 (English)In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 6, no 1, p. 60-68Article, review/survey (Refereed) Published
Abstract [en]

Insomnia and obstructive sleep apnoea (OSA) are more prevalent in patients with type 2 diabetes than in the general population. Both insomnia and OSA have been linked to cardiometabolic alterations (eg, hypertension, increased activity of the sympathetic nervous system, and systemic insulin resistance) that can exacerbate the pathophysiology of type 2 diabetes. Improvement of sleep in patients with diabetes could therefore aid the treatment of diabetes. To help health practitioners choose the best clinical tool to improve their patients' sleep without detrimentally affecting glucose regulation, this Review critically analyses the effects of common treatments for insomnia and OSA on both sleep and glucose metabolism in patients with type 2 diabetes. These treatments include pharmaceutical sleep aids (eg, benzodiazepine receptor agonists, melatonin) and cognitive behavioural therapy for insomnia, continuous positive airway pressure for OSA, and lifestyle interventions.

National Category
Endocrinology and Diabetes Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-342756 (URN)10.1016/S2213-8587(17)30233-4 (DOI)000423799900020 ()28844889 (PubMedID)
Funder
Novo NordiskSwedish Research CouncilAFA InsuranceSwedish Society of MedicineThe Swedish Brain FoundationÅke Wiberg FoundationLars Hierta Memorial Foundation
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-05-08Bibliographically approved
Cai, G.-H., Janson, C., Theorell-Haglöw, J., Benedict, C., Elmståhl, S., Lind, L. & Lindberg, E. (2018). Both Weight at Age 20 and Weight Gain Have an Impact on Sleep Disturbances Later in Life: Results of the EpiHealth Study. Sleep, 41(1), Article ID zsx176.
Open this publication in new window or tab >>Both Weight at Age 20 and Weight Gain Have an Impact on Sleep Disturbances Later in Life: Results of the EpiHealth Study
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2018 (English)In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 41, no 1, article id zsx176Article in journal (Refereed) Published
Abstract [en]

Study Objectives: Obesity is often associated with impaired sleep, whereas the impact of body mass index (BMI) at younger age and previous weight gain on sleep problems remains unknown.

Methods: The present study utilized data from the Swedish EpiHealth cohort study. A total of 15 845 participants (45-75 years) filled out an internet-based questionnaire. BMI was calculated from both measured data at study time and self-reported data at age 20 from the questionnaire.

Results: Sleep-related symptoms were most common among obese individuals (BMI >30 kg/m(2)). An association between weight gain and sleep problems was found and those with a low BMI at age 20 were most vulnerable to weight gain when it came to risk of sleep problems. Among those who were underweight (BMI <18.5 kg/m(2)) at age 20, weight gain (kg/year) was associated with difficulties initiating sleep with an adjusted OR of 2.64 (95% CI: 1.51-4.62) after adjusting for age, sex, smoking, alcohol consumption, physical activity, education, and civil status. The corresponding adjusted OR's among those who had been normal weight (BMI 18.5-24.99) and overweight (BMI 25-29.99 kg/m(2)) at age 20 were 1.89 (1.47-2.45) and 1.02 (0.48-2.13), respectively. Also difficulties maintaining sleep and snoring were most strongly related to weight gain among those who were underweight at age 20 with decreasing odds with increasing BMI at that age.

Conclusions: Sleep problems are related to weight gain and obesity. The impact of weight is most pronounced among those who had a low BMI when young.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS INC, 2018
Keywords
epidemiology, insomnia, obesity, aging, weight gain, EpiHealth study, body mass index (BMI), Epworth Sleepiness Scale (ESS), sleep problems, snoring
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-342460 (URN)10.1093/sleep/zsx176 (DOI)000422879100012 ()
Funder
Swedish Research Council
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-02-26Bibliographically approved
Chapman, C. D., Benedict, C. & Schiöth, H. B. (2018). Experimenter gender and replicability in science. Science Advances, 4(1), Article ID e1701427.
Open this publication in new window or tab >>Experimenter gender and replicability in science
2018 (English)In: Science Advances, ISSN 0036-8156, E-ISSN 2375-2548, Vol. 4, no 1, article id e1701427Article, review/survey (Refereed) Published
Abstract [en]

There is a replication crisis spreading through the annals of scientific inquiry. Although some work has been carried out to uncover the roots of this issue, much remains unanswered. With this in mind, this paper investigates how the gender of the experimenter may affect experimental findings. Clinical trials are regularly carried out without any report of the experimenter's gender and with dubious knowledge of its influence. Consequently, significant biases caused by the experimenter's gender may lead researchers to conclude that therapeutics or other interventions are either overtreating or undertreating a variety of conditions. Bearing this in mind, this policy paper emphasizes the importance of reporting and controlling for experimenter gender in future research. As backdrop, it explores what we know about the role of experimenter gender in influencing laboratory results, suggests possible mechanisms, and suggests future areas of inquiry.

National Category
Neurosciences Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:uu:diva-352930 (URN)10.1126/sciadv.1701427 (DOI)000426694200010 ()
Funder
Swedish Research Council
Available from: 2018-06-08 Created: 2018-06-08 Last updated: 2018-06-08Bibliographically approved
Rångtell, F. H., Schmidt, F., Würfel, J., Karamchedu, S., Andersson, P., Vogel, H. & Benedict, C. (2018). Morning Enzymatic Activity of DPP-4 Is Differentially Altered by Sleep Loss in Women and Men.. Diabetes Care, 41(2), e10-e11
Open this publication in new window or tab >>Morning Enzymatic Activity of DPP-4 Is Differentially Altered by Sleep Loss in Women and Men.
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2018 (English)In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 41, no 2, p. e10-e11Article in journal (Refereed) Published
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-342957 (URN)10.2337/dc17-1762 (DOI)29203582 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-03-15Bibliographically approved
Tan, X., Cedernaes, J., Forsberg, L. A., Schiöth, H. B. & Benedict, C. (2018). Self-reported sleep disturbances and prostate cancer morbidity and mortality in Swedish men: A longitudinal study over 40 years. Journal of Sleep Research
Open this publication in new window or tab >>Self-reported sleep disturbances and prostate cancer morbidity and mortality in Swedish men: A longitudinal study over 40 years
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2018 (English)In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-352162 (URN)10.1111/jsr.12708 (DOI)
Available from: 2018-06-01 Created: 2018-06-01 Last updated: 2018-06-01
Wiemerslage, L., Islam, R., van der Kamp, C., Cao, H., Olivo, G., Ence-Eriksson, F., . . . Schiöth, H. B. (2017). A DNA methylation site within the KLF13 gene is associated with orexigenic processes based on neural responses and ghrelin levels. International Journal of Obesity, 41(6), 990-994
Open this publication in new window or tab >>A DNA methylation site within the KLF13 gene is associated with orexigenic processes based on neural responses and ghrelin levels
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2017 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 41, no 6, p. 990-994Article in journal (Refereed) Published
Abstract [en]

We investigated five methylation markers recently linked to body-mass index, for their role in the neuropathology of obesity. In neuroimaging experiments, our analysis involving 23 participants showed that methylation levels for the cg07814318 site, which lies within the KLF13 gene, correlated with brain activity in the claustrum, putamen, cingulate gyrus, and frontal gyri, some of which have been previously associated to food signaling, obesity, or reward. Methylation levels at cg07814318 also positively correlated with ghrelin levels. Moreover, expression of KLF13 was augmented in the brains of obese and starved mice. Our results suggest the cg07814318 site could be involved in orexigenic processes, and also implicate KLF13 in obesity. Our findings are the first to associate methylation levels in blood with brain activity in obesity-related regions, and further support previous findings between ghrelin, brain activity, and genetic differences.

National Category
Neurosciences Endocrinology and Diabetes Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-315855 (URN)10.1038/ijo.2017.43 (DOI)000402735900024 ()28194012 (PubMedID)
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2018-02-21Bibliographically approved
Ciuculete, D.-M., Bandstein, M., Benedict, C., Waeber, G., Vollenweider, P., Lind, L., . . . Mwinyi, J. (2017). A genetic risk score is significantly associated with statin therapy response in the elderly population. Clinical Genetics, 91(3), 379-385
Open this publication in new window or tab >>A genetic risk score is significantly associated with statin therapy response in the elderly population
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2017 (English)In: Clinical Genetics, ISSN 0009-9163, E-ISSN 1399-0004, Vol. 91, no 3, p. 379-385Article in journal (Refereed) Published
Abstract [en]

The ability of statins to strongly reduce low-density lipoprotein cholesterol (LDL-C) varies interindividually and is partially influenced by genetic variants. Based on a comprehensive analysis of 23 single nucleotide polymorphisms (SNPs) known to be associated with pharmacokinetics and dynamics of statins, we developed a genetic risk score to study its impact on the therapy outcome in elderly individuals under at least 5 years statin therapy. The study was performed in a population-based cohort of 1016 elderly individuals, which comprised 168 statin users investigated at age 75 and 80. Using random forest models, the major variants influencing LDL-C levels were summarized in a weighted GRS (wGRS). The wGRS was tested with lipid and glucose outcomes and validated in an independent population-based cohort including 221 statin users. Four SNPs within the APOE cluster (rs7412, rs4420638), ABCC2 (rs2002042) and CELSR/SORT1/PSRC1 (rs646776), displayed a major impact on statin efficacy. The wGRS was significantly associated with lower LDL-C at age 75 and 80. This association was replicated displaying similar results. GRS analysis is a powerful tool to evaluate the additive effects of genetic variants on statin response and to estimate the magnitude of LDL-C reduction to a considerable extent in the older population.

Keywords
pharmacogenetics, polygenetic risk score, random forest analysis, single nucleotide polymorphism, statins
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-318494 (URN)10.1111/cge.12890 (DOI)000395007600004 ()27943270 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF)Swedish Research CouncilGlaxoSmithKline (GSK)
Available from: 2017-03-24 Created: 2017-03-24 Last updated: 2018-01-13Bibliographically approved
Tan, X., Chapman, C. D., Cedernaes, J. & Benedict, C. (2017). Association between long sleep duration and increased risk of obesity and type 2 diabetes: A review of possible mechanisms. Sleep Medicine Reviews
Open this publication in new window or tab >>Association between long sleep duration and increased risk of obesity and type 2 diabetes: A review of possible mechanisms
2017 (English)In: Sleep Medicine Reviews, ISSN 1087-0792, E-ISSN 1532-2955Article in journal (Refereed) In press
Abstract [en]

For the last two decades research has revealed an alarming association between short sleep duration and metabolic disorders. In tandem, the hormonal, behavioral, and genetic mechanisms underlying this relationship have been extensively investigated and reviewed. However, emerging evidence is revealing that excessive sleep duration has remarkably similar deleterious effects. Unfortunately, to date there has been little attention to what drives this connection. This narrative review therefore aims to summarize existing epidemiological findings, experimental work, and most importantly putative molecular and behavioral mechanisms connecting excessive sleep duration with both obesity and type 2 diabetes mellitus. It will also address recent findings suggesting a worrisome bidirectional effect such that metabolic disorders create a positive feedback loop which further perpetuates excessive sleep.

Keywords
Chronotype, Long sleep duration, Obesity, Positive feedback loop, Putative mechanisms, Type 2 diabetes mellitus
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-342958 (URN)10.1016/j.smrv.2017.11.001 (DOI)29233612 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-03-16Bibliographically approved
Cedernaes, J., Osorio, R. S., Varga, A. W., Kam, K., Schiöth, H. B. & Benedict, C. (2017). Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease.. Sleep Medicine Reviews, 31, 102-111, Article ID S1087-0792(16)00018-6.
Open this publication in new window or tab >>Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease.
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2017 (English)In: Sleep Medicine Reviews, ISSN 1087-0792, E-ISSN 1532-2955, Vol. 31, p. 102-111, article id S1087-0792(16)00018-6Article, review/survey (Refereed) Published
Abstract [en]

During wakefulness, extracellular levels of metabolites in the brain increase. These include amyloid beta (Aβ), which contributes to the pathogenesis of Alzheimer's disease (AD). Counterbalancing their accumulation in the brain, sleep facilitates the removal of these metabolites from the extracellular space by convective flow of the interstitial fluid from the para-arterial to the para-venous space. However, when the sleep-wake cycle is disrupted (characterized by increased brain levels of the wake-promoting neuropeptide orexin and increased neural activity), the central nervous system (CNS) clearance of extracellular metabolites is diminished. Disruptions to the sleep-wake cycle have furthermore been linked to increased neuronal oxidative stress and impaired blood-brain barrier function - conditions that have also been proposed to play a role in the development and progression of AD. Notably, recent human and transgenic animal studies have demonstrated that AD-related pathophysiological processes that occur long before the clinical onset of AD, such as Aβ deposition in the brain, disrupt sleep and circadian rhythms. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted sleep-wake cycles, which is able to accelerate the development and progression of this disease.

Keywords
Aging, Amyloid beta, Blood brain barrier, Circadian misalignment, Neurodegeneration, Orexin, Oxidative stress, Sleep disruption, Slow-wave sleep, Tau
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-318575 (URN)10.1016/j.smrv.2016.02.002 (DOI)26996255 (PubMedID)
Available from: 2017-03-26 Created: 2017-03-26 Last updated: 2018-01-13
Thienel, M., Wilhelm, I., Benedict, C., Born, J. & Hallschmid, M. (2017). Intranasal insulin decreases circulating cortisol concentrations during early sleep in elderly humans. Neurobiology of Aging, 54, 170-174, Article ID 170e174.
Open this publication in new window or tab >>Intranasal insulin decreases circulating cortisol concentrations during early sleep in elderly humans
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2017 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 54, p. 170-174, article id 170e174Article in journal (Refereed) Published
Abstract [en]

Aging is associated with increases in hypothalamic-pituitary-adrenal (HPA) axis activity that can predispose to metabolic and cognitive impairments. We investigated in elderly and young subjects whether intranasal insulin administration to the human brain reduces early-sleep nadir concentrations of adrenocorticotropin and cortisol, that is, indicators of baseline HPA axis activity. In within-subject comparisons, intranasal insulin (160 IU) or placebo was administered to 14 elderly (mean age 70.0 years) and 30 young (23.6 years) healthy subjects before bedtime. Sleep was polysomno-graphically assessed and blood samples were repeatedly collected. Elderly compared with young participants displayed increased early-sleep cortisol concentrations (p < 0.04) and reductions in slow wave and REM sleep (p < 0.001). Insulin administration reduced cortisol levels between 2300 hours and 0020 hours in the elderly (p = 0.03) but not young participants (p = 0.56; p = 0.003 for interaction). Findings indicate that central nervous insulin acts as an inhibitory signal in basal HPA axis activity regulation and suggest that intranasal insulin may normalize sleep-associated stress axis activity in older age.

Keywords
Insulin, Brain, Sleep, Aging, Hypothalamic-pituitary-adrenal axis, Cortisol
National Category
Neurosciences Geriatrics
Identifiers
urn:nbn:se:uu:diva-322080 (URN)10.1016/j.neurobiolaging.2017.03.006 (DOI)000399501800018 ()28385552 (PubMedID)
Funder
German Research Foundation (DFG), SFB 654
Available from: 2017-05-19 Created: 2017-05-19 Last updated: 2018-01-13Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/000-0002-8911-4068

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