Excessive daytime napping independently associated with decreased insulin sensitivity in cross-sectional study – Hyogo Sleep Cardio-Autonomic Atherosclerosis cohort study

BackgroundAlthough excessive daytime napping has been shown to be involved in diabetes occurrence, its impact on insulin secretion and sensitivity has not been elucidated. It is speculated that excessive napping disrupts the sleep-wake rhythm and increases sympathetic nerve activity during the day, resulting in decreased insulin sensitivity, which may be a mechanism leading to development of diabetes. We previously conducted a cross-sectional study that showed an association of autonomic dysfunction with decreased insulin sensitivity, though involvement of autonomic function in the association between napping and insulin sensitivity remained unclear. Furthermore, the effects of napping used to supplement to short nighttime sleep on insulin secretion and sensitivity are also unknown. In the present cross-sectional study, we examined the relationships of daytime nap duration and autonomic function with insulin secretion and sensitivity in 436 subjects enrolled in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) Cohort Study who underwent a 75-g oral glucose tolerance test (75-g OGTT), after excluding those already diagnosed with diabetes.MethodsDaytime nap duration was objectively measured using actigraphy, with the subjects divided into the short (≤1 hour) and long (>1 hour) nap groups. Insulin secretion and sensitivity were determined using 75-g OGTT findings. Standard deviation of normal to normal R-R interval (SDNN), a measure of autonomic function, was also determined based on heart rate variability. Subgroup analysis was performed for the associations of napping with insulin secretion and sensitivity, with the results stratified by nighttime sleep duration of less or greater than six hours.ResultsSubjects in the long nap group exhibited lower insulin sensitivity parameters (QUICKI: β=-0.135, p<0.01; Matsuda index: β=-0.119, p<0.05) independent of other clinical factors. In contrast, no associations with insulin secretion were found in either group. Furthermore, the association of long nap duration with insulin sensitivity was not confounded by SDNN. Specific subgroup analyses revealed more prominent associations of long nap habit with lower insulin sensitivity in subjects with a short nighttime sleep time (β=-0.137, p<0.05).ConclusionLong daytime nap duration may be a potential risk factor for decreased insulin sensitivity

Cardiac Hypertrophy and Related Dysfunctions in Cushing Syndrome Patients—Literature Review

The survival rate of adrenal Cushing syndrome patients has been greatly increased because of the availability of appropriate surgical and pharmacological treatments. Nevertheless, increased possibility of a heart attack induced by a cardiovascular event remains a major risk factor for the survival of affected patients. In experimental studies, hypercortisolemia has been found to cause cardiomyocyte hypertrophy via glucocorticoid receptor activation, including the possibility of cross talk among several hypertrophy signals related to cardiomyocytes and tissue-dependent regulation of 11β-hydroxysteroid dehydrogenase type 1. However, the factors are more complex in clinical cases, as both geometric and functional impairments leading to heart failure have been revealed, and their associations with a wide range of factors such as hypertension are crucial. In addition, knowledge regarding such alterations in autonomous cortisol secretion, which has a high risk of leading to heart attack as well as overt Cushing syndrome, is quite limited. When considering the effects of treatment, partial improvement of structural alterations is expected, while functional disorders are controversial. Therefore, whether the normalization of excess cortisol attenuates the risk related to cardiac hypertrophy has yet to be fully elucidated

Plasma brain-derived neurotrophic factor and reverse dipping pattern of nocturnal blood pressure in patients with cardiovascular risk factors.

Basic studies have shown that brain-derived neurotrophic factor (BDNF) has critical roles in the survival, growth, maintenance, and death of central and peripheral neurons, while it is also involved in regulation of the autonomic nervous system. Furthermore, recent clinical studies have suggested potential role of plasma BDNF in the circulatory system.We investigated the mutual relationships among plasma BDNF, patterns of nocturnal blood pressure changes (dippers, non-dippers, extra-dippers, and reverse-dippers), and cardiac autonomic function as determined by heart rate variability (HRV).This was a cross-sectional study of patients registered in the Hyogo Sleep Cardio-Autonomic Atherosclerosis (HSCAA) Study from October 2010 to November 2012.Two-hundred fifty patients with 1 or more cardiovascular risk factor(s) (obesity, smoking, presence of cardiovascular event history, hypertension, dyslipidemia, diabetes mellitus, chronic kidney disease) were enrolled.Plasma BDNF levels (natural logarithm transformed) were significantly (p = 0.001) lower in reverse-dipper patients (7.18±0.69 pg/ml, mean ± SD, n = 36) as compared to dippers (7.86±0.86 pg/ml, n = 100). Multiple logistic regression analysis showed that BDNF (odds ratios: 0.417, 95% confidence interval: 0.228-0.762, P = 0.004) was the sole factor significantly and independently associated with the reverse-dippers as compared with dippers. Furthermore, plasma BDNF level was significantly and positively correlated with the time-domain (SDNN, SDANN5, CVRR) and frequency-domain (LF) of HRV parameters. Finally, multiple logistic regression analyses showed that the relationship between plasma BDNF and the reverse-dippers was weakened, yet remained significant or borderline significant even after adjusting for HRV parameters.Low plasma BDNF was independently associated with patients showing a reverse-dipper pattern of nocturnal blood pressure, in which an imbalance of cardiac autonomic function may be partly involved

Associations of Sleep Quality and Awake Physical Activity with Fluctuations in Nocturnal Blood Pressure in Patients with Cardiovascular Risk Factors.

BACKGROUND:Sleep quality and awake physical activity are important behavioral factors involved in the occurrence of cardiovascular diseases, potentially through nocturnal blood pressure (BP) changes. However, the impacts of quantitatively measured sleep quality and awake physical activity on BP fluctuation, and their relationships with several candidate causal factors for nocturnal hypertension are not well elucidated. METHODS:This cross-sectional study included 303 patients registered in the HSCAA study. Measurements included quantitatively determined sleep quality parameters and awake physical activity obtained by actigraph, nocturnal systolic BP (SBP) fall [100 × (1- sleep SBP/awake SBP ratio)], apnea hypopnea index, urinary sodium and cortisol secretion, plasma aldosterone concentration and renin activity, insulin resistance index, parameters of heart rate variability (HRV), and plasma brain-derived neurotrophic factor (BDNF). RESULTS:Simple regression analysis showed that time awake after sleep onset (r = -0.150), a parameter of sleep quality, and awake physical activity (r = 0.164) were significantly correlated with nocturnal SBP fall. Among those, time awake after sleep onset (β = -0.179) and awake physical activity (β = 0.190) were significantly and independently associated with nocturnal SBP fall in multiple regression analysis. In a subgroup of patients without taking anti-hypertensive medications, both time awake after sleep onset (β = -0.336) and awake physical activity (β = 0.489) were more strongly and independently associated with nocturnal SBP falls. CONCLUSION:Sleep quality and awake physical activity were found to be significantly associated with nocturnal SBP fall, and that relationship was not necessarily confounded by candidate causal factors for nocturnal hypertension

Plasma brain-derived neurotrophic factor concentration is a predictor of chronic kidney disease in patients with cardiovascular risk factors – Hyogo Sleep Cardio-Autonomic Atherosclerosis study

<div><p>Background</p><p>Brain-derived neurotrophic factor (BDNF) has been shown to have protective effects against cardiovascular diseases and death through neural and non-neural pathways via tropomyosin-related kinase B signaling. However, it is not known whether plasma BDNF concentration is a predictor of chronic kidney disease (CKD).</p><p>Design</p><p>This study was conducted as a prospective cohort study as part of the Hyogo Sleep Cardio-Autonomic Atherosclerosis.</p><p>Methods</p><p>We measured plasma BDNF concentration in 324 patients without CKD, defined as an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73m², and with cardiovascular risk factors. As potential confounders, sleep condition, nocturnal hypertension, and autonomic function were quantitatively examined. The patients were followed for a median 37 months (range 2–59 months) and occurrence of CKD was noted.</p><p>Results</p><p>Plasma BDNF concentration was significantly and independently associated with CKD development, which occurred in 38 patients (11.7%). Kaplan-Meier analysis revealed that patients with reduced plasma BDNF concentration exhibited a significantly (p = 0.029) greater number of CKD events as compared to those with a higher concentration. Moreover, comparisons of key subgroups showed that the risk of CKD in association with low plasma BDNF concentration was more prominent in patients with a greater reduction of nocturnal systolic blood pressure, better movement index, higher standard deviations of the NN(RR) interval or average NN(RR) interval for each 5-minute period, and without past cardiovascular disease events, smoking habit, or albuminuria.</p><p>Conclusions</p><p>Plasma BDNF concentration is an independent predictor for development of CKD in patients with cardiovascular risk factors.</p></div

Plasma BDNF independently associated with reverse-dipper pattern of nocturnal blood pressure change.

<p>Multiple logistic regression analyses were performed. The covariates included age, male sex, classical cardiovascular risk factors (body mass index, current smoking, cardiovascular disease history, dyslipidemia, diabetes mellitus, eGFR), medical hypertension treatment (calcium-channel blocker, α or β blocker, ACE inhibitor or ARB, diuretic agent), AHI and BDNF. BDNF was natural logarithm-transformed (ln) to achieve a normal distribution. OR; odds ratio, CI; confidence interval, eGFR; estimated glomerular filtration rate, ACE: angiotensin converting enzyme, ARB; angiotensin receptor blocker, AHI; apnea hypopnea index, BDNF; brain-derived neurotrophic factor.</p

Correlation coefficients between nocturnal SBP fall and clinical factors.

<p>Correlation coefficients between nocturnal SBP fall and clinical factors.</p