Dysregulated 24 h melatonin secretion associated with intrinsically photosensitive retinal ganglion cell function in diabetic retinopathy: a cross-sectional study.

AIMS/HYPOTHESIS: The aim of this study was to explore whether diabetic retinopathy is associated with alterations of the circadian system, and to examine the role of reduced intrinsically photosensitive retinal ganglion cell (ipRGC) function. METHODS: Participants with type 2 diabetes, with diabetic retinopathy (n=14) and without diabetic retinopathy (n=9) underwent 24 h blood sampling for melatonin and cortisol under controlled laboratory conditions. ipRGC function was inferred from the post-illumination pupil response (PIPR). Habitual sleep duration, efficiency and variability were assessed by actigraphy. RESULTS: Participants with diabetic retinopathy compared to participants without diabetic retinopathy had smaller PIPR (p=0.007), lower 24 h serum melatonin output (p=0.042) and greater day-to-day sleep variability (p=0.012). By contrast, 24 h cortisol profiles, sleep duration and efficiency were similar in both groups. Six individuals with diabetic retinopathy had no detectable dim-light melatonin onset. PIPR correlated with 24 h mean melatonin levels (r=0.555, p=0.007). CONCLUSIONS/INTERPRETATION: ipRCG dysfunction in diabetic retinopathy is associated with disruptions of the 24 h melatonin rhythm, suggesting circadian dysregulation in diabetic retinopathy.

Disruption of the circadian rhythm of melatonin: A biomarker of critical illness severity.

Circadian dysrhythmias occur commonly in critically ill patients reflecting variable effects of underlying illness, ICU environment, and treatments. We retrospectively analyzed the relationship between clinical outcomes and 24-h urinary 6-sulfatoxymelatonin (aMT6s) excretion profiles in 37 critically ill patients with shock and/or respiratory failure. Nonlinear regression was used to fit a 24-h cosine curve to each patient's aMT6s profile, with rhythmicity determined by the zero-amplitude test. From these curves we determined acrophase, amplitude, phase, and night/day ratio. After assessing unadjusted relationships, we identified the optimal multivariate models for hospital survival and for discharge to home (vs. death or transfer to another facility). Normalized aMT6s rhythm amplitude was greater (p = 0.005) in patients discharged home than in those who were not, while both groups exhibited a phase delay. Patients with rhythmic aMT6s excretion were more likely to survive (OR 5.25) and be discharged home (OR 8.89; p < 0.05 for both) than patients with arrhythmic profiles, associations that persisted in multivariate modelling. In critically ill patients with shock and/or respiratory failure, arrhythmic and/or low amplitude 24-h aMT6s rhythms were associated with worse clinical outcomes, suggesting a role for the melatonin-based rhythm as a novel biomarker of critical illness severity.

A meta-analysis of the associations between insufficient sleep duration and antibody response to vaccination.

Vaccination is a major strategy to control a viral pandemic. Simple behavioral interventions that might boost vaccine responses have yet to be identified. We conducted meta-analyses to summarize the evidence linking the amount of sleep obtained in the days surrounding vaccination to antibody response in healthy adults. Authors of the included studies provided the information needed to accurately estimate the pooled effect size (ES) and 95% confidence intervals (95% CI) and to examine sex differences.1,2,3,4,5,6,7 The association between self-reported short sleep (<6 h/night) and reduced vaccine response did not reach our pre-defined statistical significant criteria (total n = 504, ages 18-85; overall ES [95% CI] = 0.29 [-0.04, 0.63]). Objectively assessed short sleep was associated with a robust decrease in antibody response (total n = 304, ages 18-60; overall ES [95% CI] = 0.79 [0.40, 1.18]). In men, the pooled ES was large (overall ES [95% CI] = 0.93 [0.54, 1.33]), whereas it did not reach significance in women (overall ES [95% CI] = 0.42 [-0.49, 1.32]). These results provide evidence that insufficient sleep duration substantially decreases the response to anti-viral vaccination and suggests that achieving adequate amount of sleep during the days surrounding vaccination may enhance and prolong the humoral response. Large-scale well-controlled studies are urgently needed to define (1) the window of time around inoculation when optimizing sleep duration is most beneficial, (2) the causes of the sex disparity in the impact of sleep on the response, and (3) the amount of sleep needed to protect the response.

Sleep and circadian rhythms: pillars of health-a Keystone Symposia report.

The human circadian system consists of the master clock in the suprachiasmatic nuclei of the hypothalamus as well as in peripheral molecular clocks located in organs throughout the body. This system plays a major role in the temporal organization of biological and physiological processes, such as body temperature, blood pressure, hormone secretion, gene expression, and immune functions, which all manifest consistent diurnal patterns. Many facets of modern life, such as work schedules, travel, and social activities, can lead to sleep/wake and eating schedules that are misaligned relative to the biological clock. This misalignment can disrupt and impair physiological and psychological parameters that may ultimately put people at higher risk for chronic diseases like cancer, cardiovascular disease, and other metabolic disorders. Understanding the mechanisms that regulate sleep circadian rhythms may ultimately lead to insights on behavioral interventions that can lower the risk of these diseases. On February 25, 2021, experts in sleep, circadian rhythms, and chronobiology met virtually for the Keystone eSymposium "Sleep & Circadian Rhythms: Pillars of Health" to discuss the latest research for understanding the bidirectional relationships between sleep, circadian rhythms, and health and disease.

Obstructive Sleep Apnea, Glucose Tolerance, and ß-Cell Function in Adults With Prediabetes or Untreated Type 2 Diabetes in the Restoring Insulin Secretion (RISE) Study.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with insulin resistance and has been described as a risk factor for type 2 diabetes. Whether OSA adversely impacts pancreatic islet ß-cell function remains unclear. We aimed to investigate the association of OSA and short sleep duration with ß-cell function in overweight/obese adults with prediabetes or recently diagnosed, treatment-naive type 2 diabetes. RESEARCH DESIGN AND METHODS: Two hundred twenty-one adults (57.5% men, age 54.5 ± 8.7 years, BMI 35.1 ± 5.5 kg/m2) completed 1 week of wrist actigraphy and 1 night of polysomnography before undergoing a 3-h oral glucose tolerance test (OGTT) and a two-step hyperglycemic clamp. Associations of measures of OSA and actigraphy-derived sleep duration with HbA1c, OGTT-derived outcomes, and clamp-derived outcomes were evaluated with adjusted regression models. RESULTS: Mean ± SD objective sleep duration by actigraphy was 6.6 ± 1.0 h/night. OSA, defined as an apnea-hypopnea index (AHI) of five or more events per hour, was present in 89% of the participants (20% mild, 28% moderate, 41% severe). Higher AHI was associated with higher HbA1c (P = 0.007). However, OSA severity, measured either by AHI as a continuous variable or by categories of OSA severity, and sleep duration (continuous or <6 vs. ≥6 h) were not associated with fasting glucose, 2-h glucose, insulin sensitivity, or ß-cell responses. CONCLUSIONS: In this baseline cross-sectional analysis of the RISE clinical trial of adults with prediabetes or recently diagnosed, untreated type 2 diabetes, the prevalence of OSA was high. Although some measures of OSA severity were associated with HbA1c, OSA severity and sleep duration were not associated with measures of insulin sensitivity or ß-cell responses.

Circadian Misalignment of the 24-hour Profile of Endocannabinoid 2-Arachidonoylglycerol (2-AG) in Obese Adults.

CONTEXT: The endocannabinoid (eCB) system partly controls hedonic eating, a major cause of obesity. While some studies suggested an overactivation of the eCB system in obesity, peripheral levels of eCBs across the 24-hour cycle have not been characterized in obese individuals despite the fact that in lean adults, levels of the eCB 2-arachidonoylglycerol (2-AG) vary across the day. OBJECTIVE: We sought to examine 24-hour profiles of serum concentrations of 2-AG in healthy obese and nonobese adults, under well-controlled laboratory conditions. We also simultaneously assessed 24-hour profiles of 2-oleoylglycerol (2-OG), leptin, and cortisol in each participant. DESIGN: With fixed light-dark and sleep-wake cycles, blood sampling was performed over an entire 24-hour period, including identical meals at 0900, 1400, and 1900. PARTICIPANTS: Twelve obese (8 women, mean body mass index [BMI]: 39.1 kg/m2) and 15 nonobese (6 women; mean BMI: 23.6 kg/m2) healthy adults were studied. RESULTS: We observed a 24-hour variation of 2-AG levels in obese individuals but, relative to nonobese adults, the amplitude was dampened and the timings of the nadir and peak were delayed by 4 to 5 hours. The profile of 2-OG was similarly misaligned. In contrast, when expressed relative to the 24-hour mean level, the 24-hour rhythm of cortisol and leptin were similar in obese and nonobese participants. CONCLUSIONS: Obesity appears to be associated with a dampening and delay of the 24-hour variation of eCB activity relative to the central circadian signal as well as to the daily leptin rhythm. This misalignment may play a role in the pathophysiology of obesity.

The association of sleep disturbances with glycemia and obesity in youth at risk for or with recently diagnosed type 2 diabetes.

OBJECTIVE: Poor sleep may increase obesity and type 2 diabetes (T2D) risk in youth. We explored whether subjective sleep duration, sleep quality, or risk for obstructive sleep apnea (OSA) are associated with glycemia, body mass index (BMI), or blood pressure (BP) in overweight/obese youth. METHODS: Two-hundred and fourteen overweight/obese youth of 10 to 19 years of age at risk for or recently diagnosed with T2D who were screened for the Restoring Insulin Secretion (RISE) Study had a 2-hour oral glucose tolerance test (OGTT) and completed a Cleveland Adolescent Sleepiness questionnaire and a Sleep Disturbances Scale questionnaire. Independent associations between sleep variables and measures of glycemia, BMI, and BP were evaluated with regression models. RESULTS: The multiethnic cohort was 67% female, 14.1 ± 2.1 years, and BMI 35.9 ± 6.5 kg/m2 . Habitual sleep duration <8 hours was reported in 74%. Daytime sleepiness was reported in 51%, poor sleep quality in 26%, and 30% had high obstructive sleep apnea (OSA) risk. Daytime sleepiness was associated with higher HbA1c (0.2%, P = .02) and 2-hour glucose (13.6 mg/dL, P < .05). Sleep duration, sleep quality, and OSA risk were not associated with the evaluated outcomes. Poor sleep quality and OSA risk were associated with higher BMI (2.9 kg/m2 , P = .004 and 2.83 kg/m2 , P < .003, respectively). CONCLUSIONS: In overweight/obese youth with or at risk for T2D, daytime sleepiness was associated with higher HbA1c. In addition, poor sleep quality and OSA risk were associated with higher BMI. These findings support intervention studies aimed at improving sleep quality in obese youth.

Interconnection between circadian clocks and thyroid function.

Circadian rhythmicity is an approximately 24-h cell-autonomous period driven by transcription-translation feedback loops of specific genes, which are referred to as 'circadian clock genes'. In mammals, the central circadian pacemaker, which is located in the hypothalamic suprachiasmatic nucleus, controls peripheral circadian clocks. The circadian system regulates virtually all physiological processes, which are further modulated by changes in the external environment, such as light exposure and the timing of food intake. Chronic circadian disruption caused by shift work, travel across time zones or irregular sleep-wake cycles has long-term consequences for our health and is an important lifestyle factor that contributes to the risk of obesity, type 2 diabetes mellitus and cancer. Although the hypothalamic-pituitary-thyroid axis is under the control of the circadian clock via the suprachiasmatic nucleus pacemaker, daily TSH secretion profiles are disrupted in some patients with hypothyroidism and hyperthyroidism. Disruption of circadian rhythms has been recognized as a perturbation of the endocrine system and of cell cycle progression. Expression profiles of circadian clock genes are abnormal in well-differentiated thyroid cancer but not in the benign nodules or a healthy thyroid. Therefore, the characterization of the thyroid clock machinery might improve the preoperative diagnosis of thyroid cancer.

Association of Self-Reported Sleep and Circadian Measures With Glycemia in Adults With Prediabetes or Recently Diagnosed Untreated Type 2 Diabetes.

OBJECTIVE: Sleep disturbances and circadian misalignment (social jet lag, late chronotype, or shift work) have been associated with worse glycemic control in type 2 diabetes (T2D). Whether these findings apply to adults with prediabetes is yet unexplored. We hypothesized that self-reported short sleep, poor sleep quality, and/or circadian misalignment are associated with higher glycemia, BMI, and blood pressure (BP) in adults with prediabetes or recently diagnosed, untreated T2D. RESEARCH DESIGN AND METHODS: Our cohort included 962 overweight/obese adults ages 20-65 years with prediabetes or recently diagnosed, untreated T2D who completed a 2-h oral glucose tolerance test and validated sleep questionnaires. Independent associations of sleep and circadian variables with glycemia, BMI, and BP were evaluated with regression models. RESULTS: The multiethnic cohort was 55% men, with mean ± SD age 52.2 ± 9.5 years and BMI 34.7 ± 5.5 kg/m2. Mean sleep duration was 6.6 ± 1.3 h. Poor sleep quality was reported by 54% and high risk for obstructive sleep apnea by 64%. HbA1c was significantly higher in those reporting <5 or >8 h sleep per night. Sleep duration >8 h was also associated with higher fasting glucose and <6 h with higher BMI. Shift work was also associated with higher BMI. Social jet lag and delayed chronotype were associated with higher BP. CONCLUSIONS: In our cohort, self-reported short and long sleep were both associated with adverse measures of glycemia, and short sleep and shift work were associated with higher BMI. Further research using objective measures of sleep is needed to better delineate the relationship between sleep and glycemia in adults with prediabetes or T2D.

Sex Differences in the Impact of Obstructive Sleep Apnea on Glucose Metabolism.

Objectives: Obstructive sleep apnea (OSA) is more prevalent in men and is an independent risk factor for type 2 diabetes. We aimed to determine if there are sex differences in the impact of OSA on glucose metabolism in nondiabetic overweight and obese adults. Methods: One hundred and forty-five men and women (age 33.4 ± 0.6, BMI 37.2 ± 0.7, 70.3% blacks) from the community underwent in-laboratory polysomnography. Severity of OSA was assessed by the apnea-hypopnea index (AHI). Glucose tolerance was assessed using fasting glucose, 1-h glucose, 2-h glucose and the area under the curve (AUC) during the 2-h oral glucose tolerance test (OGTT). Fasting insulin resistance was assessed by HOMA-IR, and insulin sensitivity during the OGTT was assessed by the Matsuda Index. Pancreatic beta-cell function was assessed by fasting HOMA-%B and by AUCinsulin/glucose, insulinogenic index, and oral disposition index (DIoral) during the OGTT. All comparisons were adjusted for age, BMI, race and severity of OSA. Results: There were no significant demographic differences between men and women without OSA. Men and women with OSA were similar in age, BMI, and severity of OSA, but there were more black women with OSA. Compared to women with OSA, men with OSA had significantly higher fasting glucose, 1-h glucose levels, AUCglucose, and AUC for insulin secretion rate (AUCISR) but similar 2-h glucose levels. These differences persisted in adjusted analyses. Men with OSA secreted significantly more insulin than women with OSA in order to achieve similar glucose levels. Men with OSA had significantly worse beta cell function as measured by the DIoral than women with OSA. In contrast, there were no significant sex differences in measures of glucose tolerance and beta-cell function in participants without OSA. Conclusion: Men with OSA secreted more insulin compared to women with OSA in order to maintain glucose homeostasis. The adverse impact of OSA on beta-cell responsiveness was larger in men, which may result in an overall greater risk of type 2 diabetes compared to women.

Determinants of Slow-Wave Activity in Overweight and Obese Adults: Roles of Sex, Obstructive Sleep Apnea and Testosterone Levels.

Background: Slow-wave activity (SWA) in non-rapid eye movement (NREM) sleep, obtained by spectral analysis of the electroencephalogram, is a marker of the depth or intensity of NREM sleep. Higher levels of SWA are associated with lower arousability during NREM sleep and protect against sleep fragmentation. Multiple studies have documented that SWA levels are higher in lean women, compared to age-matched lean men, but whether these differences persist in obese subjects is unclear. Obstructive sleep apnea (OSA), a condition associated with obesity, is more prevalent in men than in women. Sex differences in SWA could therefore be one of the factors predisposing men to OSA. Furthermore, we hypothesized that higher levels of testosterone may be associated with lower levels of SWA. Objective: The aim of the current study was to identify sex differences in the determinants of SWA in young and middle-aged overweight and obese adults. Methods: We enrolled 101 overweight and obese but otherwise healthy participants from the community (44 men, 57 women) in this cross-sectional study. Participants underwent an overnight in-laboratory polysomnogram. The recordings were submitted to sleep staging and spectral analysis. Sex differences and the potential contribution of testosterone levels were evaluated after adjusting for age, body mass index and race/ethnicity. Results: OSA was present in 66% of men and in 44% of women. After adjustment for differences in age, race/ethnicity and BMI, the odds ratio for OSA in men vs. women was 3.17 (95% CI 1.14-9.43, p = 0.027). There was a graded inverse relationship between the apnea-hypopnea index (AHI) and SWA in men (ß = -0.21, p = 0.018) but not in women (ß = 0.10, p = 0.207). In a multivariate regression model, higher testosterone levels were independently associated with lower SWA in men after controlling for age, race/ethnicity and apnea-hypopnea index (ß = -0.56, p = 0.025). Conclusion: Increasing severity of OSA was associated with significant decrease in sleep intensity in men but not in women. Higher testosterone levels were associated with lower sleep intensity in men. Men with higher testosterone levels may therefore have lower arousal thresholds and higher ventilatory instability in NREM sleep, and be at greater risk of OSA.

Sleep influences on obesity, insulin resistance, and risk of type 2 diabetes.

A large body of epidemiologic evidence has linked insufficient sleep duration and quality to the risk of obesity, insulin resistance and type 2 diabetes. To address putative causal mechanisms, this review focuses on laboratory interventions involving several nights of experimental sleep restriction, fragmentation or extension and examining metabolically relevant outcomes. Sleep restriction has been consistently shown to increase hunger, appetite and food intake, with the increase in caloric intake in excess of the energy requirements of extended wakefulness. Findings regarding decreases in hormones promoting satiety or increases in hormones promoting hunger have been less consistent, possibly because of confounding effects of changes in adiposity when energy intake was not controlled and sampling protocols that did not cover the entire 24-h cycle. Imaging studies revealed alterations in neuronal activity of brain regions involved in food reward. An adverse impact of experimental sleep restriction on insulin resistance, leading to reduced glucose tolerance and increased diabetes risk, has been well-documented. There is limited evidence indicating that sleep fragmentation without reduction in sleep duration also results in a reduction in insulin sensitivity. The adverse metabolic outcomes of sleep disturbances appear to involve multiple mechanistic pathways acting in concert. Emerging evidence supports the benefits of behavioral, but not pharmacological, sleep extension on appetite and glucose metabolism. Further research should focus on the feasibility and efficacy of strategies to optimize sleep duration and quality on obesity and diabetes risk in at-risk populations as well as those with established diseases. Further work is needed to identify mechanistic pathways.

Shared Genetic Control of Brain Activity During Sleep and Insulin Secretion: A Laboratory-Based Family Study.

Over the past 20 years, a large body of experimental and epidemiologic evidence has linked sleep duration and quality to glucose homeostasis, although the mechanistic pathways remain unclear. The aim of the current study was to determine whether genetic variation influencing both sleep and glucose regulation could underlie their functional relationship. We hypothesized that the genetic regulation of electroencephalographic (EEG) activity during non-rapid eye movement sleep, a highly heritable trait with fingerprint reproducibility, is correlated with the genetic control of metabolic traits including insulin sensitivity and ß-cell function. We tested our hypotheses through univariate and bivariate heritability analyses in a three-generation pedigree with in-depth phenotyping of both sleep EEG and metabolic traits in 48 family members. Our analyses accounted for age, sex, adiposity, and the use of psychoactive medications. In univariate analyses, we found significant heritability for measures of fasting insulin sensitivity and ß-cell function, for time spent in slow-wave sleep, and for EEG spectral power in the delta, theta, and sigma ranges. Bivariate heritability analyses provided the first evidence for a shared genetic control of brain activity during deep sleep and fasting insulin secretion rate.

Habitual sleep and kidney function in chronic kidney disease: the Chronic Renal Insufficiency Cohort study.

Physiological evidence suggests that sleep modulates kidney function. Our objective was to examine the cross-sectional association between kidney function and objectively-estimated habitual sleep duration, quality and timing in a cohort of patients with mild to moderate chronic kidney disease. This study involved two US clinical centers of the Chronic Renal Insufficiency Cohort (CRIC) study, including 432 participants in a CRIC ancillary sleep study. Habitual sleep duration, quality and timing were measured using wrist actigraphy for 5-7 days. Validated sleep questionnaires assessed subjective sleep quality, daytime sleepiness and risk of sleep apnea. Kidney function was assessed with the estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration equation, and the urinary protein to creatinine ratio. Lower estimated glomerular filtration rate was associated with shorter sleep duration (-1.1 mL min-1  1.73 m-2 per hour less sleep, P = 0.03), greater sleep fragmentation (-2.6 mL min-1  1.73 m-2 per 10% higher fragmentation, P < 0.001) and later timing of sleep (-0.9 mL min-1  1.73 m-2 per hour later, P = 0.05). Higher protein to creatinine ratio was also associated with greater sleep fragmentation (approximately 28% higher per 10% higher fragmentation, P < 0.001). Subjective sleep quality, sleepiness and persistent snoring were not associated with estimated glomerular filtration rate or protein to creatinine ratio. Thus, worse objective sleep quality was associated with lower estimated glomerular filtration rate and higher protein to creatinine ratio. Shorter sleep duration and later sleep timing were also associated with lower estimated glomerular filtration rate. Physicians treating patients with chronic kidney disease should consider inquiring about sleep and possibly sending for clinical sleep assessment. Longitudinal and interventional trials are needed to understand causal direction.

The Association of Sleep Duration and Quality with CKD Progression.

Evidence suggests that sleep disorders are common in individuals with CKD, but the influence of sleep duration and quality on CKD progression is unknown. We examined the association of habitual sleep duration and quality with CKD progression in 431 Chronic Renal Insufficiency Cohort (CRIC) Study participants, of whom 48% were women and 50% had diabetes (mean age of 60 years old, mean eGFR =38 ml/min per 1.73 m2, and median urine protein-to-creatinine ratio [UPCR] =0.20 g/g). We assessed sleep duration and quality by 5-7 days of wrist actigraphy and self-report. Primary outcomes were incident ESRD, eGFR slope, log-transformed UPCR slope, and all-cause death. Participants slept an average of 6.5 hours per night; mean sleep fragmentation was 21%. Over a median follow-up of 5 years, we observed 70 ESRD events and 48 deaths. In adjusted analyses, greater sleep fragmentation associated with increased ESRD risk (hazard ratio, 1.04; 95% confidence interval, 1.01 to 1.07 per 1% increase in fragmentation). In adjusted mixed effects regression models, shorter sleep duration (per hour less) and greater sleep fragmentation (per 1% more) each associated with greater eGFR decline (-1.12 and -0.18 ml/min per 1.73 m2 per year, respectively; P=0.02 and P<0.01, respectively) and greater log UPCR slope (0.06/yr and 0.01/yr, respectively; P=0.02 and P<0.001, respectively). Self-reported daytime sleepiness associated with increased risk for all-cause death (hazard ratio, 1.11; 95% confidence interval, 1.02 to 1.20 per one-point increase in the Epworth Sleepiness Scale score). These findings suggest that short and poor-quality sleep are unrecognized risk factors for CKD progression.

Effects of Insufficient Sleep on Pituitary-Adrenocortical Response to CRH Stimulation in Healthy Men.

Study Objectives: Severe sleep restriction results in elevated evening cortisol levels. We examined whether this relative hypercortisolism is associated with alterations in the pituitary-adrenocortical response to evening corticotropin-releasing hormone (CRH) stimulation. Methods: Eleven subjects participated in 2 sessions (2 nights of 10 hours vs. 4 hours in bed) in randomized order. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 09:00 to 24:00 for adrenocorticotropic hormone (ACTH) and cortisol measurements, and perceived stress was assessed hourly. Ovine CRH was injected at 18:00 (1 µg/kg body weight). Results: Prior to CRH injection, baseline ACTH, but not cortisol, levels were elevated after sleep restriction. Relative to the well-rested condition, sleep restriction resulted in a 27% decrease in overall ACTH response to CRH (estimated by the incremental area under the curve from 18:00 to 24:00; p = .002) while the cortisol response was decreased by 21% (p = .083). Further, the magnitude of these decreases was correlated with the individual amount of sleep loss (ACTH: rSp = -0.65, p = .032; cortisol: rSp = -0.71, p = .015). The acute post-CRH increment of cortisol was reduced (p = .002) without changes in ACTH reactivity, suggesting decreased adrenal sensitivity. The rate of decline from peak post-injection levels was reduced for cortisol (p = .032), but not for ACTH. Scores of perceived stress were unaffected by CRH injection and were low and similar under both sleep conditions. Conclusions: Sleep restriction is associated with a reduction of the overall ACTH and cortisol responses to evening CRH stimulation, and a reduced reactivity and slower recovery of the cortisol response.

Association Between Inpatient Sleep Loss and Hyperglycemia of Hospitalization.

OBJECTIVE: To determine whether inpatient sleep duration and efficiency are associated with a greater risk of hyperglycemia in hospitalized patients with and without diabetes. RESEARCH DESIGN AND METHODS: In this retrospective analysis of a prospective cohort study, medical inpatients ≥50 years of age were interviewed, and their charts were reviewed to obtain demographic data and diagnosis. Using World Health Organization criteria, patients were categorized as having normal blood glucose, impaired fasting blood glucose, or hyperglycemia based on morning glucose from the electronic health record. Wrist actigraphy measured sleep. Multivariable ordinal logistic regression models, controlling for subject random effects, tested the association between inpatient sleep duration and proportional odds of hyperglycemia versus impaired fasting blood glucose or impaired fasting blood glucose versus normal blood glucose in hospitalized adults. RESULTS: A total of 212 patients (60% female and 74% African American) were enrolled. Roughly one-third (73, 34%) had diabetes. Objective inpatient sleep measures did not differ between patients with or without diabetes. In ordinal logistic regression models, each additional hour of in-hospital sleep was associated with an 11% (odds ratio 0.89 [95% CI 0.80, 0.99]; P = 0.043) lower proportional odds of a higher glucose category the next morning (hyperglycemia vs. elevated and elevated vs. normal). Every 10% increase in sleep efficiency was associated with an 18% lower proportional odds of a higher glucose category (odds ratio 0.82 [95% CI 0.74, 0.89]; P < 0.001). CONCLUSIONS: Among medical inpatients, both shorter sleep duration and worse sleep efficiency were independently associated with greater proportional odds of hyperglycemia and impaired fasting glucose.