Cortisol Profiles Research Articles

No effect of infant nursery rearing on laboratory rhesus monkey dams’ social behavior or long-term cortisol profiles

While the behavioral and physiological impacts of nursery rearing in laboratory-housed infant monkeys have been well characterized, to date no studies have examined the impact on nonhuman primate dams of their infants being removed for rearing in the nursery. Despite the lack of evidence on the topic, anti-animal research groups often cite mother-infant separation and infant nursery rearing (NR) as a welfare concern for laboratory monkey mothers. As such, important policy decisions regarding research activities may result without adequate evidence. Therefore, we designed this study to examine behavioral and hormonal responses in laboratory monkey dams, who were part of independent long-term longitudinal studies, in response to their infants being NR or mother-peer-reared (MPR). We assessed social, self-care, environmental exploration, and abnormal behaviors for 30 days before and 30 days after parturition in rhesus monkey dams (Macaca mulatta, N=49). Infants were randomly assigned to be either NR (N = 27) or MPR (N = 22). We also analyzed hair samples for cortisol concentrations three times across the study period (Pregnancy, Neonatal Period, Peak Lactation). Dams of NR infants showed no gross behavioral differences relative to dams of MPR infants (all p’s>0.05). Dams of MPR infants showed expected increases in social grooming and social contact, and concomitant decreases in foraging and locomotion, in the 30 days post-partum compared to the 30 days pre-partum (p<0.01). Dams whose infants were NR or MPR showed no differences in hair cortisol concentrations across the study period (p>0.05). We conclude that, with respect to the behavioral and endocrine measures we assessed, nursery rearing of their infants is not detrimental to the welfare of laboratory-housed macaque dams.

8342 A Rare Case of a Corticotropic and Gonadotropic Pituitary Double Adenoma

Abstract Disclosure: S. Gruber: None. D. Kirschenbaum: None. T. Hortobagyi: None. C. Serra: None. A. Bink: None. F. Beuschlein: None. Z. Erlic: None. Background: Pituitary adenomas account for about 15% of all intracranial neoplasms and typically arise from monoclonal proliferation of anterior pituitary cells. While lactotropic and clinically hormone-inactive adenomas make up by far the largest proportion, somatotropic and corticotropic adenomas have a significantly lower prevalence. This case describes the very rare finding of a corticotropic and gonadotropic double adenoma. Clinical Case: A 63-year-old Caucasian man (BMI 36.7 kg/m2) presented in the obesity clinic. Hypercortisolism was suspected by repeated lack of cortisol suppression in low-dose dexamethasone suppression tests [minimal 87 nmol/l] and disrupted circadian rhythm of cortisol secretion according to salivary cortisol profile. Cortisol levels in a 24-hour sample of urine were normal. ACTH levels were elevated [73 ng/l; n&amp;lt;61 ng/l] leading to suspicion of Morbus Cushing. Concomitant diseases include sleep apnea, arterial hypertension and newly diagnosed type 2 diabetes mellitus. Medical history was notable for deep vein thrombosis and pulmonary embolism. Other stigmata of hypercortisolism were not evident. The rest of endocrine work up confirmed partial secondary hypothyroidism and hypogondotropic hypogonadism. An MRI of the pituitary gland revealed a pituitary macroadenoma with a maximum dimension of 20 mm. The patient underwent an endoscopic transnasal adenomectomy with post-operative corticotropic insufficiency. Contrary to our expectations, the histological examination of the surgical resection revealed a gonadotrophic pituitary adenoma with SF1 and focal FSH expression. The discrepancy between clinical, biochemical and histological findings led to subsequent examinations of the specimen with detection of an small fragment accounting for less than 5% of the total sample with expression of T-Pit and ACTH but neither SF1 nor Pit-1, corresponding to an additional corticotropic adenoma with densely granulated pattern. The tumor cells did not show overlapping expression patterns of transcription factors or hormones, which indicates the coincidence of two distinct adenomas. Three months postoperatively, the patient is biochemically cured. Partial anterior pituitary insufficiency remained. Conclusion: Pituitary double adenomas are found in 0.5-1.5% of all surgical specimens. They are characterized by their origin from different cell lines, which distinguishes them from plurihormonal adenomas, which originate from one single cell line. Here we demonstrate a SF1-T-Pit lineage combination resulting in a neighboring ACTH and FSH-adenoma. In this particular case, the clinically relevant corticotropic adenoma was comparatively tiny, making it easy to miss. This illustrates well the importance of careful correlation of clinical, laboratory and histologic findings as correct diagnosis is crucial for postoperative patient management. Presentation: 6/2/2024

Hatha yoga reduces momentary stress but does not impact diurnal profiles of salivary cortisol and alpha-amylase: A randomized controlled trial

Does the practice of yoga impact stress? Various studies have suggested that yoga may reduce both self-reported stress and stress biomarkers, but the evidence for such claims remains inconclusive, especially for yoga styles with a focus on physical postures. In a randomized controlled trial with 98 participants, we therefore examined whether an eight-week Hatha yoga intervention (60 min, 3×/week or more) led to reduced levels of diurnal salivary cortisol (sCort), salivary alpha-amylase (sAA), and subjective momentary stress as compared to a waitlist control group. To ensure the concomitant assessment of self-report and biological measures in an ecologically valid setting, and to capture the diurnal profile of cortisol and alpha-amylase, we employed an ecological momentary assessment approach. Five times per day, participants reported their momentary stress levels on a visual analogue scale and collected saliva samples for the assessment of salivary biomarkers. The intervention led to a significant reduction of subjective momentary stress but there was no change in diurnal sCort or sAA levels. There are several potential explanations for these findings: The intervention may have helped participants to cope better with stress while leaving diurnal levels of stress biomarkers unaffected, or the change may at least not have been reflected in sCort and sAA. Alternatively, there may have been a self-report bias, insofar as a favorable disposition towards yoga may have led participants to report reductions in stress in order to indicate positive effects of the intervention. Our findings contribute to a better understanding of the effects of distinct yoga interventions, demonstrating their potential to serve as low-risk stress relief tools.

Diurnal Cortisol Profiles Across Pregnancy: Challenges in the Current State of Knowledge

Diurnal Cortisol Profiles Across Pregnancy: Challenges in the Current State of Knowledge

Cortisol and insulin behaviors during an ultramarathon event: are they real markers of extreme exertion?

The current work aimed to describe and compare the cortisol and insulin concentrations behavior and rate of perceived exertion (RPE) during a 115 km ultramarathon race. Nine ultrarunners (eight males) were evaluated six times (0, 37, 60, 76, 89 and 115 km). At each moment, saliva samples (for cortisol and insulin assessment) and RPE (CR10 scale) were collected. Statistical analysis included correlation, one-way repeated measure ANOVA, and Statistical Parametric Mapping to define discrete and continues changes and compare cortisol, insulin and RPE profiles. Our main findings revealed an early peak in cortisol and RPE, accompanied by a decline in insulin responses (402±49 min of the race, P<0.05). Cortisol and insulin only showed magnitude differences with inverse behaviors until ~6% (7 km) of the ultramarathon duration. Cortisol and RPE presented similar behaviors, rising from the beginning of the race and remaining elevated throughout the race (η2=0.91 and η2=1.0, P<0.001). Insulin levels decreased when the race started, remaining below 60% of baseline values from the midpoint to the end of the race (P=0.04). The study showed an imbalance in the catabolic/anabolic hormone profile during an ultramarathon race, with a prominence in catabolic state. It should be considered in the ultramarathon races preparation and participation due to its possible detrimental effect on the athlete's health.

167 Using ‘omics’ to optimize nutrition and health outcomes

Abstract It is clear that diet is linked with health outcomes, yet we are still far from fully understanding the impact of diet on systemic metabolic health. In the new era of ‘omics’ technology, the ability to optimize nutrition across the lifespan of companion animals is within reach. We have been using ‘omics’ technologies to understand how changes in diet composition impact metabolism using a neonatal piglet model. By measuring the composition of sow milk over the first week of lactation, we created an optimized pig milk replacer, and studied the impact of varying the whey protein composition of the milk replacer using a combination of metabolomics on blood, urine, liver, and brain tissue, as well as transcriptomics of intestinal, liver and brain tissue. Our results revealed a substantial impact of the type of whey protein on piglet metabolism that included differences in cortisol, blood and tissue amino acid profiles, and immunity. This work paves the way for additional studies to optimize animal nutrition in the neonatal period and beyond.

Diurnal cortisol profiles in autistic adolescents and young adults: Associations with social difficulties and internalizing mental health symptoms.

Several autism-related characteristics, such as social difficulties, may contribute to high perceived stress and increased exposure to stressful life events in some autistic individuals. Repeated exposure to stress might lead to the dysfunction of the hypothalamic-pituitary-adrenocortical-axis and be a vulnerability factor for developing mental health difficulties. Previous studies show contradictory findings on salivary cortisol in autism. In the current study, we investigated diurnal cortisol profiles in autistic adolescents and young adults, as well as their associations with social difficulties, stress exposure, and mental health symptoms. Autistic (n = 48, Mage = 17.6) and nonautistic (n = 51, Mage = 18.4) participants collected salivary cortisol at home six times a day for 2 days. Social difficulties, exposure to stressful life events/bullying, and mental health symptoms were assessed with questionnaires and clinical interviews. Similar diurnal cortisol slopes (DCS) and cortisol awakening responses were observed between the groups, but autistic participants showed higher total cortisol output (AUCG, area under the curve with respect to ground) during the day (b = 19.09, p = 0.009). In the autistic group, more severe social difficulties were associated with flatter DCS (b = 0.01, p = 0.007). Finally, cortisol alterations were associated with self-reported mental health symptoms, especially in autistic females in analyses uncorrected for multiple comparisons. In conclusion, our results do not indicate autism-related group-level alterations in most diurnal cortisol measures, but autistic youth showed higher total cortisol (AUCG) compared with nonautistic peers. More detailed investigation of interindividual variability in cortisol profiles within autistic people might give us important insights into vulnerability to developing stress-related mental health difficulties.

Sleep, Health Outcomes and Body Weight (SHOW) study: a measurement burst design study on sleep and risk factors for obesity in black emerging adults in North Carolina, USA

IntroductionBlack emerging adults (18–28 years) have the highest risk of short sleep duration and obesity. This increased risk may be partly explained by greater stress levels, which may result from...

Self-Compassion is Associated with Improved Well-Being and Healthier Cortisol Profiles in Undergraduate Students

ObjectivesStress is highly prevalent in college students. Self-compassion, the tendency to respond in a caring manner to one’s own suffering or failures, reduces psychological distress and promotes mental health. Self-compassion may also influence physiological manifestations of stress; however, research is limited. Among undergraduate students over the course of an academic semester, we explored the associations of self-compassion with stress-related psychological variables including measures of affect, anxiety, and depressive symptoms. We also examined daily patterns of salivary cortisol over four days: diurnal slope, mean, and day-to-day cortisol rhythm stability.MethodThis sample of undergraduate students from introductory psychology courses in a large United States Midwestern university was predominantly non-Hispanic White (71.2%) and female (86.4%). All data were collected prior to final exams. After providing baseline psychosocial data, participants engaged in a 2-week mindfulness intervention: They were provided an iPod loaded with audio tracks based on the well-known Mindfulness-Based Stress Reduction intervention, but received no face-to-face instruction. Fifty-nine participants provided self-report demographic and medical data and completed the saliva sampling regimen over the first 4 days of the intervention. Diurnal salivary cortisol was assessed immediately after waking and again at bedtime over four consecutive days.ResultsHierarchical multiple regressions replicated previous findings showing that self-compassion is associated with higher positive and lower negative affect, lower perceived stress, and fewer symptoms of anxiety and depression. Regression models controlling for oral contraception and tobacco use revealed a positive association of self-compassion with healthy cortisol profiles marked by steeper diurnal cortisol slopes and increased regularity of the inter-daily cortisol slope.ConclusionsThese results confirm that self-compassion may be protective against the psychological and physiological manifestations of stress in college. Kind and compassionate responses to one’s own struggles may shield students from the adverse effects of stress. The potential mechanisms underlying these associations are worthy of future research.PreregistrationThis study is not preregistered.

Arginine-Vasotocin Neuronal System in Steindachneridion parahybae (Siluriformes: Pimelodidae) and Its Influence on Artificially Induced Spawning in Captivity

This study summarizes new data on induced spawning of Steindachneridion parahybae, focusing on the aggressive behavior of females. This study characterizes the vasotocinergic system using immunohistochemistry, highlighting the potential influence of arginine-vasotocin (AVT) on reproductive physiology. Two experimental groups were proposed: (A) control, with one female in the aquarium, and (B) experimental, with two females in the same aquarium. Dominant (D) females presented a more aggressive behavior and did not show any injury. They apparently had a length and body mass higher than injured nondominant (ND) females. The analysis identified positive AVT immunoreactive (ir) neurons exclusively within the preoptic area, including parvocellular, magnocellular, and gigantocellular subpopulations, containing fibers-ir extending into the pituitary gland. Cellular and nuclear areas were greater in D compared to ND in the magnocellular subpopulation. There were no differences between parvocellular and gigantocellular subpopulations. There was a difference on the steroid plasma profile of cortisol (more in ND than in D) and 17α,20β-dihydroxy-4-pregnen-3-one (more in D than in ND). Furthermore, control and D females presented higher optical densities for AVT-ir, gonadotropin-releasing hormone-ir, and luteinizing hormone-ir than ND. In general, there were no differences in the results of female (control group) with D females. The AVT system is highly complex, possibly counting multiple sites of action during artificial reproduction and acting directly and/or indirectly associated with behavioral and physiological changes in S. parahybae females when induced to spawning.

Circadian and ultradian rhythms: Clinical implications.

The hypothalamic-pituitary-adrenal axis is an extremely dynamic system with a combination of both circadian and ultradian oscillations. This state of 'continuous dynamic equilibration' provides a platform that is able to anticipate events, is sensitive in its response to stressors, remains robust during perturbations of both the internal and external environments and shows plasticity to adapt to a changed environment. In this review, we describe these oscillations of glucocorticoid (GC) hormones and why they are so important for GC-dependent gene activation in the brain and liver, and their consequent effects on the regulation of synaptic and memory function as well as appetite control and metabolic regulation. Abnormalities of mood, appetite and metabolic regulation are well-known consequences of GC therapy, and we suggest that the pattern of GC treatment and hormone replacement should be a much higher priority for endocrinologists and the pharmaceutical industry. One of the major impediments to our research on the importance of these cortisol rhythms in our patients has been our inability to measure repeated levels of hormones across the day in patients in their home or work surroundings. We describe how new wearable methodologies now allow the measurement of 24-h cortisol profiles - including during sleep - and will enable us to define physiological normality and allow us both to develop better diagnostic tests and inform, at an individual patient level, how to improve replacement therapy.

Daytime plasma cortisol and cortisol response to dexamethasone suppression are associated with a prothrombotic state in hypertension.

A prothrombotic state was demonstrated in patients with Cushing's syndrome and is involved in the development and progression of cardiovascular and renal damage in hypertensive patients. This study was designed to examine the relationships between cortisol secretion and the hemostatic and fibrinolytic systems in hypertension. In 149 middle-aged, nondiabetic, essential hypertensive patients free of cardiovascular and renal complications, we measured hemostatic markers that express the spontaneous activation of the coagulation and fibrinolytic systems and assessed daily cortisol levels (8 AM, 3 PM, 12 AM; area under the curve, AUC-cortisol) together with the cortisol response to dexamethasone overnight suppression (DST-cortisol). Plasma levels of D-dimer (D-dim), prothrombin fragment 1+2 (F1+2), and von Willebrand factor (vWF) were progressively and significantly higher across tertiles of AUC-cortisol and DST-cortisol, whereas no differences were observed in fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor-1, antithrombin III, protein C, and protein S. D-dim, F1+2, and vWF were significantly and directly correlated with age and both AUC-cortisol and DST-cortisol. Multivariate regression analysis showed that both AUC-cortisol and DST-cortisol were related to plasma D-dim, F1+2, and vWF independently of age, body mass index, blood pressure, and renal function. Greater daily cortisol profile and cortisol response to overnight suppression are independently associated with a prothrombotic state in hypertensive patients and might contribute to the development of organ damage and higher risk of cardiovascular complications.

Functional Gastrointestinal Symptoms in Children with Autism and ADHD: Profiles of Hair and Salivary Cortisol, Serum Leptin Concentrations and Externalizing/Internalizing Problems.

Functional Gastrointestinal Disorders (FGIDs) present a higher prevalence in individuals with Neurodevelopmental Disorders (NDDs). The Stress System and the Gut-Brain axis (GBA) may mediate these relations. We aimed to assess the prevalence and profile of FGIDs in a clinical sample of children with Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD) compared to typically developing children (TD) as well as to investigate possible relations between stress-related biomarkers and internalizing/externalizing problems in children with NDDS. In total, 120 children, aged between 4 and 12 years old, formed three groups (N = 40, each): ADHD, ASD and TD. Salivary cortisol, hair cortisol and serum leptin were measured. The ASD group had more FGID problems than the TD group (p = 0.001). The ADHD and ASD groups had higher total internalizing/externalizing problems than the TD group (p < 0.0001, p < 0.0001, p = 0.005, respectively). Children with FGIDs showed more total, internalizing and externalizing problems compared to children without FGIDs (p < 0.0001, p < 0.0001, p = 0.041, respectively). The ADHD group showed lower AUCg values (p < 0.0001), while the hair cortisol was higher for the TD group (p < 0.0001). In conclusion, children with NDDs had more FGID symptoms and present higher internalizing and externalizing problems. Children with ADHD and FGIDs had more internalizing problems compared to those without FGIDs. No differences in stress-related biomarkers were shown to differentiate children with NDDs with and without FGIDs. Future prospective studies including a greater number of children may elucidate the biological pathways linking these comorbidities.

The role of social-evaluative threat for cortisol profiles in response to psychosocial stress: A person-centered approach.

Heterogeneity in individuals' physiological stress responses is central to theories linking stress with vulnerability to disease. Although multiple cortisol profiles have been reported in response to acute psychological stress, most prior work focuses on a single, average pattern and relative deviations from it, such as greater or lesser response peaks or reactivity. The present aims were to identify cortisol stress response trajectory classes using a data-driven approach and test whether social-evaluative threat (SET), a reliable elicitor of cortisol, predicted a greater likelihood of membership in the more reactive profiles. Data were pooled from 13 acute laboratory stressor studies from two geographically distinct U.S. university communities. Participants included 1,258 adults ranging from 18 to 52 years (Mage = 20.5; 62% women; 38% men) with diverse racial/ethnic identities and socioeconomic statuses. Studies included a version of the Trier Social Stress Test and at least three salivary cortisol assessments. SET was tested in three ways: study conditions with evaluators present, perceptions of evaluation, and ratings of shame-related emotions. Latent group-based trajectory modeling was applied to identify cortisol response patterns that best fit the data. Results revealed five unique cortisol response profiles. Consistent with hypotheses, SET conditions, greater perceived evaluation, and greater shame-related emotions predicted membership in the most reactive response trajectories. The findings highlight the high degree of heterogeneity that characterizes cortisol stress response profiles, which has important implications for theories of stress and health and methodological approaches in future research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Supplemental Material for The Role of Social-Evaluative Threat for Cortisol Profiles in Response to Psychosocial Stress: A Person-Centered Approach

Supplemental Material for The Role of Social-Evaluative Threat for Cortisol Profiles in Response to Psychosocial Stress: A Person-Centered Approach

Altered coordination between sleep timing and cortisol profiles in night working female hospital employees

BackgroundCortisol typically peaks in the morning after waking up and declines throughout the day, reaching its lowest levels during nighttime sleep. Shift work can cause misalignment between cortisol levels and sleep-wake timing. We analyzed this misalignment in female shift workers focusing on the timing and extent of these changes. MethodsWe conducted a cross-sectional study involving 68 shift workers (aged 37 ± 10 years) and 21 non-shift workers (aged 45 ± 10 years) from a hospital. Shift workers were monitored through two day shifts and three night shifts, whereas non-shift workers were monitored during two day shifts. Each participant collected six to eight saliva samples (depending on their shift type) and provided sleep timing information, which was recorded via polysomnography and sleep diaries. Generalized additive mixed models were used to estimate shift-specific differences in cortisol smooth curves. Summary measures calculated for the cortisol smooth curves included cortisol awakening response, peak-to-bed slope, and total output. ResultsBetween shift workers and non-shift workers, we observed similar diurnal cortisol profiles with a steep negative diurnal slope during day shifts. In shift workers on night shifts, a flattened U-shaped cortisol profile after the post-awakening maximum was observed, with a peak-to-bed slope close to zero. When comparing night to day shifts in the group of shift workers, mean cortisol levels were lower between 42 and 56 minutes and 1.8–11.9 hours after waking up, and higher between 14.9 and 22 hours after waking up. ConclusionOur findings indicate altered cortisol profiles in female hospital employees on night shifts. Specifically, cortisol levels were lower at night when higher levels would typically be necessary for work activities, and higher at bedtime after a night shift, when levels should normally be low.

Stress-free blood sampling in minipigs: A novel method for assessing 24-h cortisol profiles and drug effects on diurnal and ultradian rhythms

We developed a novel, stress-free blood sampling method for minipigs, allowing continuous cortisol monitoring over 24 h. Baseline cortisol levels exhibited both ultradian and diurnal rhythms. During nighttime, smaller ultradian rhythms overlaid a lower baseline cortisol, which increased in sleeping pigs before lights were turned on. Additionally, we developed an analytical tool based on the R package “pracma” to quantify ultradian peak and circadian components of the cortisol profiles.To validate our model, we investigated the effects of Verucerfont, a CRH receptor antagonist, and Venlafaxine, a serotonin-norepinephrine reuptake inhibitor. Verucerfont reduced cortisol levels during the first 9 h without affecting diurnal rhythm. Cortisol peak parameters decreased, with a 31% reduction in overall area under the curve (AUC) and a 38% reduction in ultradian average AUC. Ultradian peaks decreased from 7 to 4.5, with 34% lower amplitude. Venlafaxine maintained plasma concentrations within the targeted human effective range.This method enables us to enhance our understanding of cortisol regulation and provide valuable insights for the impact of investigation drugs on the diurnal and ultradian rhythms of cortisol.

Comparative analysis of salivary cortisol measurements using different assay methods in relation to serum-free cortisol measurement

ObjectivesSalivary cortisol reflects the biologically active form of serum cortisol, offering a noninvasive evaluation method for the diurnal rhythm of the hypothalamic-pituitary-adrenal (HPA) axis. While liquid chromatography-tandem mass spectrometry (LC-MS/MS) is known for its specificity, immunoassays (IA) are commonly used because of their simplicity. This study aimed to assess the performance of salivary cortisol measurement using both IA and LC-MS/MS in comparison to serum-free cortisol measurement. MethodsAssay results for 188 saliva and 94 serum samples from 47 participants were analyzed. Salivary samples collected at different time points were analyzed using IA and LC-MS/MS. Serum samples were analyzed for cortisol, cortisol-binding globulin, and free cortisol. The statistical analyses included correlations and method comparisons. ResultsThe diurnal salivary cortisol profiles exhibited a comparable circadian rhythm pattern; however, the concentrations measured using IA were consistently higher than those measured using LC-MS/MS. The correlation analysis revealed robust associations among salivary cortisol (IA), salivary cortisol (LC-MS/MS), and serum-free cortisol levels (LC-MS/MS). However, the method comparison revealed a systematic bias between IA and LC-MS/MS in salivary cortisol measurement. ConclusionsThis study contributes to the ongoing debate on assay techniques by affirming the suitability of IA and LC-MS/MS for salivary cortisol measurement to assess dynamic changes in HPA axis activity. The identified systematic bias emphasizes the importance of selecting methods based on specific research or clinical requirements.

Serial Diurnal Salivary Cortisol Profiles in 667 Pregnant Women-Association With Cardiometabolic Complications.

Maternal obesity, hypertensive pregnancy disorders, and gestational diabetes (GDM) are linked to an increased risk of negative offspring health outcomes. This association may be mediated by maternal hypothalamic-pituitary-adrenal axis (HPA axis) activity, resulting in elevated maternal cortisol levels and fetal exposure, but evidence remains scarce. We (1) examined maternal diurnal cortisol profiles longitudinally across gestation, and (2) explored associations with maternal cardiometabolic complications. Women in the InTraUterine sampling in early pregnancy (ITU) study (n = 667) provided 7 salivary cortisol samples from awakening to bedtime up to 3 times during pregnancy (median gestational week 19.3, 25.7, and 38.1; n = 9356 samples). Changes in cortisol awakening response (CAR) and diurnal slope (indicative of HPA axis activity) and their associations with maternal body mass index (BMI), hypertensive pregnancy disorders and GDM were examined using linear mixed models. The CAR declined in 60% to 67% of women, and the diurnal slope attenuated from early to late pregnancy (b = 0.006; P = .001). Higher BMI was associated with less decline in CAR (b = 0.031; P = .0004) and less attenuation in diurnal slope from early to late pregnancy (b = -0.001; P = .006). Hypertensive pregnancy disorders and GDM were not significantly associated with diurnal cortisol profiles. The attenuation in CAR and diurnal slope support HPA axis hyporesponsivity during pregnancy. Less attenuation of both markers in women with a higher BMI may indicate reduced adaption of the HPA axis to pregnancy, presenting a mechanistic link to offspring health outcomes.

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

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. 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. 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). ipRCG dysfunction in diabetic retinopathy is associated with disruptions of the 24 h melatonin rhythm, suggesting circadian dysregulation in diabetic retinopathy.