Significance of genetic factors for the plasma insulin response to glucose in healthy subjects

The intravenous glucose tolerance and plasma insulin response to glucose infusion were analysed in a twin and family material, comprising 279 healthy subjects. The relation between the blood glucose and plasma insulin values was studied by an analysis of the principal eigenvalues. The variables obtained were corrected for sex, age and weight, and standardized with regard to mean and variance. The results showed that at least four of the variables have appreciable familial correlations, corresponding to a heritability (h²) varying between 0.38 and 0.72. These correlations could not be accounted for by common environment alone. Thus, the beta cell function in normal man, as measured by a glucose challenge test, appears to be genetically regulated.     

Postprandial glucose and insulin responses to meals containing different carbohydrates in normal and diabetic subjects

To examine whether the form of dietary carbohydrate influences glucose and insulin responses, we studied the glucose and insulin responses to five meals--each containing a different form of carbohydrate but all with nearly identical amounts of total carbohydrate, protein, and fat--in 10 healthy subjects, 12 patients with Type I diabetes, and 10 patients with Type II diabetes. The test carbohydrates were glucose, fructose, sucrose, potato starch, and wheat starch. In all three groups, the meal containing sucrose as the test carbohydrate did not produce significantly greater peak increments in the plasma concentration of glucose or greater increments in the area under the plasma glucose-response curves than did meals containing potato, wheat, or glucose as test carbohydrates. Urinary excretion of glucose in patients with diabetes was not significantly greater after the sucrose meal. The meal containing fructose as the test carbohydrate produced the smallest increments in plasma glucose levels, but the differences were not always statistically significant. In healthy subjects and patients with Type II diabetes, peak serum concentrations of insulin were not significantly different in response to the five test carbohydrates. Our data do not support the view that dietary sucrose, when consumed as part of a meal, aggravates postprandial hyperglycemia.     

Plasma adiponectin response to acute exercise in healthy subjects

Adipose tissue secretes adiponectin, an adipocytokine that is involved in the regulation of insulin sensitivity. Following acute exercise, insulin sensitivity has been shown to increase. Increased adiponectin following exercise may be related to the change in insulin sensitivity. The purpose of the present study was to characterize the effect of a single cycle exercise session on adiponectin and to compare the exercise effects between healthy male and female subjects. Plasma concentrations of adiponectin, tissue necrosis factor-alpha (TNF-), insulin, glucose, and leptin were assessed before and immediately after a 60-minute stationary cycle ergometry session at 65% of O_2max. Male and female subjects were matched for cardiorespiratory fitness and body composition and dietary intake was controlled for the three days prior to the exercise trial. At rest, adiponectin concentration was not associated with percentage body fat, body mass index (BMI), fitness, or resting plasma variables (P>0.05). Following exercise, neither male nor female subjects exhibited changes in adiponectin or leptin concentrations (P>0.05). TNF- exhibited a time main effect increase with exercise (P<0.05), but there were no gender differences. These results suggest that plasma adiponectin concentrations do not change with exercise in healthy male or female subjects. Results are given as mean (SE).     

Glottis constriction response in healthy subjects

The purpose of this study was to evaluate the glottis constriction response induced by a sudden and involuntary increase in gastric and oesophageal pressures by Tll-Ll intervertebral magnetic stimulation of the abdominal muscle roots in nine healthy subjects. Twitch flow, twitch gastric, and oesophageal pressures were measured after abdominal muscle root stimulation, which allowed pharyngo-laryngeal muscle activation to be characterized. Pharyngeal endoscopies were performed on five subjects to assess vocal cord movements. All stimulations induced positive gastric and oesophageal pressures and expiratory flow, which increased with stimulation intensity (flow: R=0.32; p<0.0001; oesophageal pressure: R=0.26; p=0.001; gastric pressure: R=0.37; p<0.0001). Twitch gastric pressure and twitch oesophageal pressure were negatively correlated with twitch flow (respectively, R=-0.183, p<0.05; R=-0.35, p<0.0001). Upper airway resistance was higher at peak oesophageal pressure than at peak flow (p<0.001). Peak twitch gastric and twitch oesophageal pressure latencies were similar (133+/-4ms and 122+/-4ms) but longer than peak twitch flow and EMG latencies (62+/-2ms and 73+/-4ms, p<0.0001). Glottis constriction following magnetic abdominal muscle root stimulation was seen in all subjects during endoscopy, with a latency estimated at between 80 and 100ms. This method could be a new, simple tool for assessing the upper airway constriction protective reflex.     

Haemodynamic response to exercise in healthy young and elderly subjects

Whereas with advancing age, peak heart rate (HR) and cardiac index (CI) are clearly reduced, peak stroke index (SI) may decrease, remain constant or even increase. The aim of this study was to describe the patterns of HR, SI, CI, arteriovenous difference in oxygen concentration (C _a-vO₂), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), stroke work index (SWI) and mean systolic ejection rate index (MSERI) in two age groups (A: 20–30 years, n = 20; B: 50–60 years n = 20. After determination of pulmonary function, an incremental bicycle exercise test was performed, with standard gas-exchange measurements and SI assessment using electrical impedance cardiography. The following age-related changes were found: similar submaximal HR response to exercise in both groups and a higher peak HR in A than in B[185 (SD 9) vs 167 (SD 14) beats?·?min^?1, P??2, P??1?·?m^?2, P?C _a-vO₂ during exercise; higher MAP at all levels of exercise in B; higher SVRI at all levels of exercise in B; lower SWI in B after recovery; higher MSERI at all levels of exercise in A. The decrease in SI with advancing age would seem to be related to a decrease in myocardial contractility, which can no longer be compensated for by an increase in preload (as during submaximal exercise). Increases in systemic blood pressure may also compromise ventricular function but would seem to be of minor importance.     

Reproducibility of the heart rate response to low-strain Valsalva manoeuvre in healthy subjects

To elucidate whether the intrastrain cardio-acceleration and cardio-deceleration responses to low-strain Valsalva manoeuvre at expiratory pressures 10 and 20 mmHg (VM10,VM20) are reproducible, a beat-to-beat heart rate study was undertaken in 46 subjects (40 male undergraduates aged 19-25 years and six laboratory workers (four females and two males aged 28-55 years). The intensity of the heart rate response (HRR) was assessed by a ratio of the mean value of the pre-strain heart rate (Valsalva means' ratio VMR). In each subject the HRR to VM10 and VM20 was measured by repeating each manoeuvre three times. Reproducibility was evaluated on a short-term (1 h), medium-term (1 and 6 months), and long-term (6 and 11 years) basis. With the individual differences the initial short-term reproducibility study revealed either an cardio-acceleration or cardio-deceleration response to VM10 and VM20, which persisted well in the repeated tests. On the ground of this result three individual modes of HRRs to VM10 and VM20 were distinguished: (i) Mode A, a deceleration response appeared both to VM10 and VM20; (ii) Mode B, a deceleration response appeared to VM10 and an acceleration response to VM20; (iii) Mode C, an acceleration response appeared both to VM10 and VM 20. All of these modes, as well as the separate acceleration and deceleration responses, were well reproducible at any cited time points. We suggest that the individual modes of HRR are induced by different states of autonomic cardiovascular reactivity: Mode A probably expresses a parasympathotonic (vagotonic), Mode C--a sympathotonic, and Mode B--an intermediate autonomic state. Thus, the individual modes of HRR to VM10 and to VM20 could be used as a method of non-invasive determination of cardiovascular autonomic reactivity.     

Processing of expected and unexpected monetary performance outcomes in healthy older subjects

The feedback-related negativity (FRN), an event-related potential (ERP) component reflecting feedback processing in the anterior cingulate cortex (ACC), has consistently been found to be reduced in healthy aging, whereas behavioral findings regarding age-related changes in decision making and feedback-based learning are inconsistent. This study aimed to elucidate similarities and differences between healthy younger and older subjects in the processing of monetary performance feedback focusing on effects of reward expectancy. Eighteen younger and 20 older subjects completed a feedback learning task, in which a rule could be learned to predict the reward probabilities associated with particular stimuli. Older subjects showed evidence of slower learning than younger subjects. In both younger and older subjects, the amplitude difference between nonreward and reward in the FRN time window was larger for unexpected than expected outcomes, driven by modulations of negative feedback ERPs. Consistent with previous findings, the amplitude difference tended to be generally reduced in older subjects. P300 amplitude was larger for reward than nonreward in both groups, and interactions between valence and probability indicated that only the P300 for reward was modulated by expectancy. Despite general changes of outcome-related ERPs in healthy aging, older subjects show evidence of preserved effects of expectancy on the processing of monetary feedback.     

The oxidative stress in response to routine incremental cycling exercise in healthy sedentary subjects

The kinetics of blood markers of the oxidative stress during and after an incremental exercise until the maximal performances is not documented in healthy sedentary subjects. We studied subjects of both sexes cycling on an ergometer until or near the V(O)(2)(max) measurement, and we measured during exercise and a 30-min recovery period the plasma concentration of thiobarbituric acid reactive substances (TBARS) which explored the production of reactive oxygen species (ROS) and two antioxidants (plasma reduced ascorbic acid (RAA) and erythrocyte reduced glutathione (GSH)). Despite we noted inter-individual differences in the instants of maximal variations of TBARS, GSH, and RAA, they were all measured within the first 20 min of the post-exercise recovery period, and at the 30th min of recovery, the three ROS blood markers tended to recover their pre-exercise levels. The maximal TBARS increase was positively correlated with V(O)(2)(max) and negatively correlated with the magnitude of RAA consumption. Our results indicate the existence of an early post-exercise oxidative stress in healthy sedentary volunteers. They also show that the ROS production is proportional to the maximal aerobic power and inversely related to the consumption of plasma antioxidants.     

Food intolerance in duodenal ulcer patients,non ulcer dyspeptic patients and healthy subjects

Summary In 50 duodenal ulcer out-patients and 50 non ulcer dyspeptic patients suffering from low to moderate epigastric painful symptoms the intolerance of 39 foods were significantly increased compared to a group of 50 healthy subjects. Food intolerance was not different between duodenal ulcer and non ulcer dyspeptic patients. Intolerance was related in the majority of nutrients to aversion and pain or to an increased incidence of aversion alone in patients and normals. In duodenal ulcer, coffee and fruit juice were associated with an elevated incidence of pain.Abbreviations DU Duodenal ulcer - NUD Non ulcer dyspepsia - N Normal Dedicated to Professor Dr. N. Zöllner on the occasion of his 65th anniversary     

Humor attenuates the cortisol awakening response in healthy older men

This study examined the impact of an important factor contributing to successful aging, humor, on post-awakening cortisol levels among a group of 45 older men whose ages ranged from 64 years to 86 years (mean = 73.6 years). Four saliva samples were collected from the participants for 2 days immediately after waking and every 15 min thereafter for three times. Cortisol data of the 2 days were aggregated for analysis. Two separate indices of cortisol awakening response reflecting the mean level of secretion and the rise from immediately to 45 min post-awakening, AUC_G and AUC_I, were computed using the trapezoid formula. The relation of these two indices to humor (operationalized as coping) was examined in a multiple regression analysis while controlling for the effect of age, socioeconomic status, and self-esteem. Results indicated that higher humor scores were associated with lower AUC_G but had no relation with AUC_I. Findings of the present study suggest that the hypothalamic-pituitary-adrenocortical axis is the major pathway whereby positive psychological dispositions, such as humor, exert their health effects in the aging population. Moreover, cortisol levels in the awakening period may be particularly sensitive to the influences of psychosocial factors.     

Postprandial hypotension due to a lack of sympathetic compensation in patients with diabetes mellitus

Postprandial hypotension is an important hemodynamic abnormality in diabetes mellitus, but few reports are available on the relationship between autonomic dysfunction and postprandial hypotension. Ten diabetic patients and 10 healthy volunteers were recruited for this study. Postural blood pressure and heart rate changes were measured before lunch, and then the hemodynamic responses to a standardized meal were investigated. Holter electrocardiogram (ECG) monitoring was conducted for assessing spectral powers and time-domain parameters of RR variations. Postural changes from the supine to the upright position decreased the systolic blood pressure of the diabetics from 133(+/-)16 to 107(+/-)20 mmHg (p<0.01), but did not decrease the systolic blood pressure of the controls. The heart rate remained constant in the diabetics but was increased in the controls. Food ingestion decreased systolic blood pressure in the diabetics, with a maximum reduction of 25(+/-)5 mmHg. This decrease was not associated with any changes in the ratio of low frequency to high frequency, and yet the heart rate remained almost constant. Indexes involving parasympathetic tone were not affected. Food ingestion did not affect blood pressure in the control group. These findings suggest that lack of compensatory sympathetic activation is a factor contributing to postprandial hypotension in diabetics, and that parasympathetic drive does not make a significant contribution to this condition.     

Reduced neutrophil superoxide production among healthy older adults in response to acute psychological stress

Ageing is associated with higher morbidity and mortality, and declining immune function, termed immunesenescence. The present study examined the effects of an acute laboratory psychological stress task on innate immunity, specifically neutrophil function, among older adults. The two functional assays used were phagocytosis of Escherichia coli and stimulated superoxide production. Participants were 17 (11 female) older adults (mean age 75.7, SD = 7.06 years). Blood samples to determine neutrophil function by flow cytometry were taken at the end of resting baseline, during an acute stress task and during recovery. The stress task was an 8-minute time-pressured mental arithmetic challenge with social evaluation. There was a significant reduction in neutrophil superoxide production, p = .017, η²_p = .240, associated with the stress task relative to baseline, but no effect on phagocytosis. The results of this study could contribute to explaining the increased risk of infection in older adults, particularly those subject to frequent stress exposures. Future research is needed to explore the underlying mechanisms of acute stress effects on human neutrophil function in older adults in greater detail.     

Lowering Cortisol enhances growth hormone response to growth hormone releasing hormone in healthy subjects

Cortisol is known to influence growth hormone release probably by modulating somatostatin tone. We examined the effect of metyrapone (the 1 β-hydroxylase inhibitor) treatment on growth hormone response to growth hormone releasing hormone (1 μg kg^-1 body wt). Six healthy male subjects were tested on two occasions 1 wk apart. On one occasion they received metyrapone followed by growth hormone releasing hormone and on the other placebo followed by growth hormone releasing hormone. In all subjects metyrapone produced a significant drop in Cortisol levels. Together with this drop there was a significant enhancement of growth hormone response to growth hormone releasing hormone. The GH response was negatively correlated with the Cortisol level. Growth hormone release in response to growth hormone releasing hormone challenge is thus seen to be heavily influenced by Cortisol levels.     

Gap prepulse inhibition of the auditory late response in healthy subjects

The gap‐startle paradigm has been used as a behavioral method for tinnitus screening in animal studies. This study aimed to investigate gap prepulse inhibition (GPI) of the auditory late response (ALR) as the objective response of the gap‐intense sound paradigm in humans. ALRs were recorded in response to gap‐intense and no‐gap‐intense sound stimuli in 27 healthy subjects. The amplitudes of the baseline‐to‐peak (N1, P2, and N2) and the peak‐to‐peak (N1P2 and P2N2) were compared between two averaged ALRs. The variations in the inhibition ratios of N1P2 and P2N2 during the experiment were analyzed by increasing stimuli repetitions. The effect of stimulus parameter adjustments on GPI ratios was evaluated. No‐gap‐intense sound stimuli elicited greater peak amplitudes than gap‐intense sound stimuli, and significant differences were found across all peaks. The overall mean inhibition ratios were significantly lower than 1.0, where the value 1.0 indicates that there were no differences between gap‐intense and no‐gap‐intense sound responses. The initial decline in GPI ratios was shown in N1P2 and P2N2 complexes, and this reduction was nearly complete after 100 stimulus repetitions. Significant effects of gap length and interstimulus interval on GPI ratios were observed. We found significant inhibition of ALR peak amplitudes in performing the gap‐intense sound paradigm in healthy subjects. The N1P2 complex represented GPI well in terms of suppression degree and test‐retest reliability. Our findings offer practical information for the comparative study of healthy subjects and tinnitus patients using the gap‐intense sound paradigm with the ALR.     

Mathematical analysis of blood glucose and plasma insulin responses to insulin infusion in healthy and diabetic subjects

The blood glucose and plasma insulin responses during slow intravenous infusion of insulin in six normal and seven diabetic subjects were fitted to a previously described model utilizing four first-order rate constants for the glucose-insulin interactions. Certain lumped parameters of the model were shown to be characteristic of the subjects' responses and abnormalities. The predicted values of blood glucose and plasma insulin can be made to approximate the actual measurement in all subjects. Additional studies are proposed to delineate further the range of applicability of the model and to characterize diabetic instability.     

Modelling study of the acute cardiovascular response to hypocapnic hypoxia in healthy and anaemic subjects

The present study analyses the cardiovascular response to acute hypocapnic hypoxia (simulating the effect of respiration at high altitude) both in healthy, unacclimatised subjects and in subjects with moderate anaemia, by means of a mathematical model of short-term cardiovascular regulation. During severe hypoxia, cardiac output and heart rate (HR) exhibit a significant increase compared with the basal level (cardiac output: +90%; HR: +64%). Systemic arterial pressure remains quite constant or shows a mild increase. Coronary blood flow increases dramatically (+200%), thus maintaining a constant oxygen delivery to the heart. However, blood oxygen utilisation in the heart augments, to fulfil the increased power of the cardiac pump during hypoxia. Cerebral blood flow rises only at very severe hypoxia but, owing to the vasoconstrictory effect of hypocapnia, its increase (+80%) is insufficient to maintain oxygen delivery to the brain. The model suggests that a critical level for the aerobic metabolism in these organs (heart and brain) is reached at an oxygen partial pressure in arterial blood (PaO₂) of approximately 25 mmHg. Moderate anaemia during normoxia is compensated by an increase in cardiac output (+22%), a decrease in total peripheral resistance (−30%) and an increase in O₂ extraction from blood (+40%). As cardiovascular regulation mechanisms are already recruited in anaemic subjects at rest, their action soon becomes exhausted during hypocapnic hypoxia. Critical levels for vital functions are already reached at a PaO₂ of approximately 45 mmHg.     

Hourly variability of cerebrospinal fluid biomarkers in Alzheimer's disease subjects and healthy older volunteers

Large hour-to-hour variability has previously been demonstrated in the cerebrospinal fluid (CSF) concentrations of Alzheimer's disease (AD) biomarkers amyloid β(42) (Aβ(42)) and Aβ(40) in healthy younger subjects. We investigated the within-subject variability over 36 hours in CSF Aβ and tau proteins, in older subjects and AD patients. Six patients with mild stage AD (59-85 years, Mini Mental State Examination (MMSE) 16-26) and 6 healthy older volunteers (64-77 years) received an intrathecal catheter from which, during 36 hours, each hour 6 mL of CSF was drawn. Concentrations of Aβ(42), Aβ(40), total tau, and phosphorylated tau were determined and the variability was analyzed. Within-subject variability within 3-hour periods was assessed as the coefficient of variation, which was comparable for these 4 biomarkers in controls (4.2%-4.6%) and AD (3.1%-5.8%). Variability over 12 hour periods was 5.3% to 9.5%. These findings suggest that CSF biomarker variability is relatively low in healthy older controls and AD patients. Furthermore, continuous sampling of CSF proved to be a useful and robust method, which may also be used to investigate AD pathogenesis and to evaluate pharmacotherapeutic interventions.