Depressive symptoms linked to 1-h plasma glucose concentrations during the oral glucose tolerance test in men and women with the metabolic syndrome.

AIMS: The addition of the 1-h plasma glucose concentration measure from an oral glucose tolerance test to prediction models of future Type 2 diabetes has shown to significantly strengthen their predictive power. The present study examined the relationship between severity of depressive symptoms and hyperglycaemia, focusing on the 1-h glucose concentration vs. fasting and 2-h glucose measures from the oral glucose tolerance test. METHODS: Participants included 140 adults with the metabolic syndrome and without diabetes who completed a baseline psychobiological assessment and a 2-h oral glucose tolerance test, with measurements taken every 30 min. Depressive symptoms were assessed using the Beck Depression Inventory. RESULTS: Multivariate linear regression revealed that higher levels of depressive symptoms were associated with higher levels of 1-h plasma glucose concentrations after adjusting for age, gender, ethnicity, BMI, antidepressant use and high-sensitivity C-reactive protein. Results were maintained after controlling for fasting glucose as well as for indices of insulin resistance and secretion. Neither fasting nor 2-h plasma glucose concentrations were significantly associated with depressive symptoms. CONCLUSIONS: Elevated depressive symptoms in persons with the metabolic syndrome were associated with greater glycaemic excursion 1-h following a glucose load that was not accounted for by differences in insulin secretory function or insulin sensitivity. Consistent with previous findings, this study highlights the value of the 1-h plasma glucose measurement from the oral glucose tolerance test in the relation between depressive symptoms and glucose metabolism as an indicator of metabolic abnormalities not visible when focusing on fasting and 2-h post-oral glucose tolerance test measurements alone.

The effect of low-dose inhaled fluticasone propionate on exhaled nitric oxide in asthmatic patients and comparison with oral zafirlukast.

BACKGROUND: Exhaled nitric oxide (ENO) is a noninvasive marker of ongoing inflammation in asthmatic patients. Comparison between inhaled and oral anti-inflammatory medications in reduction of ENO in asthmatic patients has not been performed. OBJECTIVE: We measured changes in ENO, spirometry, need for rescue medication, quality of life (QOL), and diary scores (DS) after inhaled and oral anti-inflammatory therapy in adults with moderate asthma. METHODS: A randomized, double-blind, placebo-controlled, crossover design with 4-week washout periods was used. A plateau level of ENO, measured in parts per billion (ppb), was obtained by chemiluminescence with a Sievers 280NOA as per American Thoracic Society recommendations. Eighteen asthmatic adults (15 Hispanic, with a percentage predicted forced expiratory volume in 1 second (FEV1%) of 50% to 85%) on bronchodilators (beta2) only were studied. Subjects used fluticasone propionate (FP) metered-does inhaler (44 microg), two puffs twice daily, and matching placebo (PB) for 4 weeks. Eight of the asthmatic patients (7 Hispanic, FEV1% 50% to 85%) on bronchodilators only then received blinded zafirlukast (ZK) 20 mg and matching PB twice daily for 4 weeks. RESULTS: Low-dose inhaled FP resulted in significant improvements in ENO, spirometry, QOL, DS, and beta2 use. A significant difference in mean ENO was found (P < 0.01) before and after FP from 34+/-7 ppb to 13+/-3 ppb. A significant improvement was found (P < 0.05) with FEV1% from 75+/-3 to 85+/-3 with FP treatment. The other measured parameters, percentage predicted of peak expiratory flow rate, beta2 need, DS, and QOL measurements, were improved with low-dose FP treatment. No significant reduction was found in ENO with oral ZK for 4 weeks. After oral ZK washout and the second extension arm of placebo, ENO significantly increased back to 47+/-14 ppb (P < 0.05), but spirometry measures did not worsen. Significant improvements were found with DS and beta2 use with oral ZK therapy. CONCLUSIONS: These results reveal ENO is reduced with only low-dose inhaled FP in asthmatic patients not on anti-inflammatory medication. In the smaller extension study, ENO was reduced with FP and not with oral ZK treatment, and ENO levels increased back to near prestudy levels after ZK washout and the second extension arm of placebo. As a marker of inflammation, ENO levels reveal an improvement with anti-inflammatory medication and worsening when it is discontinued.

Modeling preclinical cardiovascular risk for use in epidemiologic studies: Miami community health study.

To develop a method for assessing preclinical cardiovascular disease risk, models of resting cardiovascular regulation and of insulin metabolic syndrome were derived from information collected from 1991 to 1996 in a culturally heterogeneous sample of 319 healthy men and women (aged 25-44 years) from Miami-Dade County, Florida. The model of resting cardiovascular regulation used 8 noninvasive measures of autonomic and cardiovascular function. Three factors were derived: 1) parasympathetic, 2) inotropy, and 3) systemic vascular resistance. The model of insulin metabolic syndrome used 12 measures assessing body mass, insulin, glucose, and lipid metabolism. Four factors were derived: 1) body mass and fat distribution, 2) glucose level and regulation, 3) insulin level and regulation, and 4) plasma lipid levels. Analyses of the association of the two models revealed that subjects with lower cardiac contractility had greater body mass, higher fasting and postload insulin and glucose levels, and lower insulin sensitivity. Subjects with greater vascular resistance had greater body mass, higher total cholesterol and triglyceride levels, and lower high density lipoprotein cholesterol levels. These findings indicate that preclinical cardiovascular disease risk may involve pathophysiologic processes in which cardiac inotropic and vasodilatory functions are linked to specific aspects of insulin metabolic syndrome.

Cardiovascular responsivity to stress in adolescents with and without persistently elevated blood pressure.

OBJECTIVES: The goal of this study was to compare the cardiovascular responses to behavioural stressors of three groups of adolescents who differed in blood pressure status across assessments. DESIGN: Casual blood pressure of adolescents who were identified as having elevated blood pressure during a school screen was re-evaluated in the laboratory. The adolescents were classified into two groups: (i) those with consistently elevated blood pressure across school and laboratory assessments and (i) those with labile blood pressure whose blood pressure in the laboratory was below 130/80 mmHg. A comparison group of adolescents with consistently normal blood pressure was also included. METHODS: Cardiovascular parameters were assessed during rest and during two behavioural stressors, the evaluated speaking task and the mirror tracing task. RESULTS: Adolescents with elevated blood pressure were more vascularly responsive across stressors than adolescents with labile blood pressure, who, in turn, were more reactive than adolescents with normal blood pressure. CONCLUSIONS: These results suggest that vascular reactivity to behavioural stressors may be useful in predicting risk of hypertension because of its sensitivity in distinguishing adolescents with consistently elevated blood pressure from those with labile blood pressure and those with normal blood pressure.

Piecewise latent growth curve modeling of systolic blood pressure reactivity and recovery from the cold pressor test.

Latent growth curve methodology was used to model systolic blood pressure reactivity and recovery from the cold pressor test. A piecewise regression approach permitted the separate but simultaneous modeling of the two components (reactivity and recovery) of the stress process. Data came from a study of 99 participants classified on the basis of gender, ethnicity, and family history of hypertension. Their systolic blood pressure was assessed at rest, during the cold pressor test, and during a task recovery period. A measure of task appraisal and readings from ambulatory blood pressure monitoring during a workday were also examined. The article illustrates a step-by-step approach to modeling reactivity and recovery. Results indicated that both reactivity and recovery were associated with subsequent systolic blood pressure at work.

Cognitive outcome of children with epilepsy and malformations of cortical development.

OBJECTIVE: To assess intellectual functioning (IQ) in 54 children and adolescents with intractable epilepsy who later underwent cortical resection due to unilateral malformations of cortical development acquired in utero. METHODS: Lesion type was classified into circumscribed mass lesions and diffuse cortical dysplasia based on histopathologic analysis of surgical tissue. Cortical dysplastic lesions were further graded as mild, moderate, or severe according to specific microscopic features. Laterality of lesion was determined through neurologic examination and electrophysiologic and neuroradiologic procedures. Classification of lesion type was corroborated by its significant relationship with other disease-related variables known to be related to clinical severity (age at seizure onset, age at resection, and extent of lesion). RESULTS: Analyses of covariance revealed that circumscribed lesions had a less deleterious effect on nonverbal IQ than did diffuse cortical dysplasia, after controlling for age at seizure onset and extent of lesion. This effect was also found on verbal IQ measures, but only in subjects with right-sided lesions. Subjects with left-sided lesions performed significantly more poorly on verbal IQ measures than those with right-sided lesions. Additionally, younger age at onset and greater extent of lesion were associated with poorer cognitive outcome. CONCLUSIONS: Cortical dysplasia and early left hemisphere lesions have a significantly worse impact on cognitive functioning than circumscribed lesions or right hemisphere developmental lesions in children with epilepsy.

Validation of the insulin sensitivity index (ISI(0,120)): comparison with other measures.

The purpose of this study was to explore possible calculations using oral glucose tolerance test (OGTT) values in order to develop a simple measure of insulin sensitivity. We devised a formula for an insulin sensitivity index, ISI(0,120), that uses the fasting (0 min) and 120 min post-oral glucose (OGTT) insulin and glucose concentrations. It appears to be generalizable across a spectrum of glucose tolerance and obesity. Most importantly, our data show that ISI(0,120) correlates well, when applied prospectively in comparative studies, with the insulin sensitivity index obtained from the euglycemic hyperinsulinemic clamp (r = 0.63, P < 0.001). This correlation was demonstrably superior to other indices of insulin sensitivity such as the HOMA formula presented by Matthews, and performed comparably to the computerized HOMA index. Measurement of insulin sensitivity has traditionally been possible only in research settings because of the invasiveness and expense of the methods used. Clinical investigators have therefore sought more practical methods to obtain an index of insulin sensitivity. Such an index should approximate insulin sensitivity as measured by the euglycemic hyperinsulinemic clamp (M). We present ISI(0,120), a simple yet sensitive measure of insulin sensitivity which is adaptable for use in clinical settings as well as large epidemiologic studies.

History of gestational diabetes, insulin resistance and coronary risk.

The purpose of this study was to examine characteristics associated with the insulin metabolic syndrome, including insulin resistance, abnormal glucose tolerance, dyslipidemia, obesity, and elevated blood pressure, among women who have experienced gestational diabetes. 39 nondiabetic, young (20-42 years), postpartum (3-18 months) white women were recruited from obstetrical clinics. Twenty-one women had a history of gestational diabetes; 18 had uncomplicated pregnancies. Multivariate analyses revealed a significant difference between groups in insulin resistance (M, measured by euglycemic clamp) and insulin levels (from an oral glucose tolerance test), with insulin resistance showing a statistically stronger difference than insulin levels. Groups also differed significantly when compared on a set of variables associated with insulin metabolic syndrome: glucose tolerance, triglycerides, blood pressure, and body-mass index. Using insulin resistance as a covariate eliminated these group differences, suggesting that insulin resistance is the key factor underlying insulin metabolic syndrome. The higher risk of later developing type 2 diabetes and hypertension in women who have a history of gestational diabetes is explicable by their poorer profile on variables associated with insulin metabolic syndrome, and appears to be attributable to insulin resistance. Thus, insulin resistance appears to distinguish young women at risk for cardiovascular disease.

Aberrant parasympathetic and hemodynamic function distinguishes a subgroup of psychologically distressed individuals with asymptomatic type-I diabetes mellitus.

In a previous study, a subgroup of asymptomatic insulin-dependent diabetic individuals (termed IDDM-2) were identified on the basis of diminished parasympathetic cardiac input and elevated heart rate at rest. When compared to another group of asymptomatic IDDM participants (termed IDDM-1), and a nondiabetic healthy control group, the IDDM-2 group displayed elevated blood pressure, supported by elevated total peripheral resistance. Measures of psychological regulation were also taken in this study, and form the basis of this article, which examined whether these IDDM-2 patients differed from the other two groups on these measures. The possible role of glycemic control, IDDM duration, and number of somatic complaints among group differences in psychological regulation was also examined. The IDDM-2 group reported increased psychological distress, as reflected by increased dysphoric or depressive symptoms, trait anxiety, perceived stress, and cynical hostility, as well as decreased optimism and interpersonal, but not family, social support. Glycemic control did not account for any of the group differences in psychological regulation. However, group differences in dysphoria and anxiety were accounted for by differences in somatic complaints, whereas differences in interpersonal social support were accounted for by IDDM duration. Moreover, none of the variables investigated accounted for the diminished optimism of the IDDM-2 group. Therefore, in individuals with IDDM, who would otherwise be considered, after medical examination, as no different from other asymptomatic IDDM individuals, the combination of diminished parasympathetic cardiac input and elevated heart rate was associated with aberrant alterations of both hemodynamic and psychological functioning; the increased psychological distress in these individuals may be influenced, in part, by increased diabetes duration and number of somatic symptoms.

The Gulf crisis experience of Kuwaiti children: psychological and cognitive factors.

This study examined a stratified random sample of 233 Kuwaiti 8- to 12-year-old boys and girls, in order to assess their level of exposure to violence during the Iraqi occupation of Kuwait and its relation to psychological and cognitive performance 1 year after the crisis. Children were assessed on intelligence, posttraumatic stress, and depression, and were interviewed about their crisis experience. No significant decline in intelligence scores was detected after the crisis. A difference in level of parental depression was found between those who stayed in Kuwait as compared to those who were out for all or part of the crisis. Depression in children was low but associated with the level of exposure to violence as reported in the interview, and greater levels of posttraumatic stress. The results support the hypothesis that acute trauma resulting from exposure to violence is related to posttraumatic stress in children.

Classification of individual differences in cardiovascular responsivity: the contribution of reactor type controlling for race and gender.

Classification of 150 normotensive or mildly hypertensive men and women into myocardial, vascular, or mild reactors was accomplished using a regression-based approach. The method was based on the participants' cardiac output (CO) and total peripheral resistance (TPR) reactivity to the speech presentation task. This task purportedly can elicit both myocardial and vascular responses. Cut-scores were based on the y-intercept from the linear regression of the CO reactivity on TPR reactivity and vice versa. A greater percentage of Black men were classified as vascular responders as compared to Black women and White participants. Groups were found to differ on cardiovascular reactivity to the speech preparation, cold pressor, and mirror tracing tasks in predictable ways, after controlling for gender and ethnicity. Groups were also differentiated by ambulatory blood pressure and hypertensive status. The study supports the classification of homogenous groups of participants based on the relative extent to which myocardial or vascular mechanisms dominate the reactivity to stress.

Cardiovascular and perceptual effects of reporting pain during the foot and forehead cold pressor tests.

In research involving the cold pressor test, a tacit presumption is often made that reporting pain during stimulation is not in itself reactive. This study examined whether, for the foot and forehead cold pressor tests, activities involved in reporting pain may affect (a) the evoked pattern of cardiovascular response, and (b) the magnitude of self-perceived pain. In 40 normotensive college men, increases in systolic blood pressure were greater during test sessions that included verbal ratings of pain, as compared to sessions in which pain was not reported. In contrast to its effect on physiological activation, reporting pain did not significantly alter the participant's perception of the painfulness of the lest, on recollection shortly after the test. We conclude, therefore, that reporting pain during the cold pressor test may impose significant additional demands on the cardiovascular system, but it does not interfere significantly with the processing of nociceptive information.

Social support and psychological distress in Kuwaiti boys and girls exposed to the Gulf crisis.

Tested hypotheses about the role of social support in the relation between trauma from the Gulf crisis experience and psychological or health distress 2 years after the crisis. Participants were 151 Kuwaiti boys and girls exposed to high or low levels of trauma during the crisis. Participants were administered the Post-Traumatic Stress Disorder Index (PTSDI), Children's Depression Inventory (CDI), and measures of social support and health complaints. Children exposed to high levels of trauma had higher PTSDI and CDI scores and more health complaints than controls. Social support did not mediate the relation between trauma and distress. However, social support and sex functioned jointly as moderators of trauma on distress. Social support was shown to buffer the effect of trauma in girls but not in boys. Boys, however, reported lower levels of support than girls. The findings underscore the importance of the appropriate model specification in studies of stress and social support.

Influence of ethnicity and gender on cardiovascular responses to active coping and inhibitory-passive coping challenges.

OBJECTIVE: The goal of this study was to evaluate how black and white men and women responded physiologically to specific laboratory challenges. METHODS: Hemodynamic responses to an active coping (evaluated speaking) and two inhibitory-passive coping (mirror tracing, cold pressor) tasks were examined in 138 black and white men and women. RESULTS: Significant ethnicity by gender interactions occurred for the evaluated speaking task. Black men responded with lower blood pressure, cardiac output or heart rate, or both, than black women, white men, and white women, who did not differ from each other. Black men, relative to the other subgroups, also reported more inhibitory-passive coping, hostility, and pessimism, and less social support. Whites also responded with greater increases in systolic blood pressure during mirror tracing than blacks. CONCLUSIONS: These findings indicate that black-white differences in physiological responsivity obtained for men may have limited generalizability for women. The results also suggest that environmental and social factors rather than genetic or constitutional factors may play a role in black-white reactivity differences.

Simultaneous single unit recording in the medial nucleus of the medial geniculate nucleus and amygdaloid central nucleus throughout habituation, acquisition, and extinction of the rabbit's classically conditioned heart rate.

The present study examined single neuron activity in the medial nucleus of the medial geniculate (mMG) and amygdaloid central nucleus (ACe) simultaneously across several phases of differential heart rate conditioning (habituation, acquisition, and extinction). Within the same animals, the magnitude of mMG and ACe unit responses to two tone conditioned stimuli (CS) exhibited habituation, differential acquisition, and extinction. Neurons in each area developed a differential response latency to the CSs during acquisition, suggesting that mMG and ACe may be involved in changes of synaptic efficacy. Units in both areas rapidly developed a differential response magnitude to the CSs (< 6 acquisition trials), however, mMG units responded to the CSs with a shorter latency than ACe units across all phases of training. This suggests that unlearned and learned CS information may access mMG before ACe. These results are consistent with the notion that conditioning-induced plasticity which occurs in mMG may influence the conditioning-induced plasticity that occurs further downstream in the amygdala.

Stimulus dimensions of the cold pressor test and the associated patterns of cardiovascular response.

Hemodynamics of the cold pressor response in relation to its pain and nonpain stimulus components were investigated in normotensive college men using the foot and forehead cold pressor tasks. Mechanisms of pain- and non-pain-related increases in blood pressure were analyzed as residual effects of concurrent changes in total peripheral resistance and cardiac output. The identified partial relationships suggested that the response pattern associated with pain included positive change both in cardiac output and in total peripheral resistance, whereas the nonpain-related response was limited to an increase in total peripheral resistance. Analyses of individual differences in cardiovascular responses to pain further indicated that pain-related increments in blood pressure were mediated by a steeper rise in total peripheral resistance, an increase in heart rate, and an apparent increase in preload. At baseline, high reactors to pain manifested relatively elevated total peripheral resistance, diminished cardiac output, and an indication of a reduced inotropic state, suggesting that altered basal homeostasis may discriminate normotensive individuals displaying heightened cardiovascular reactivity to aversive cold stimulation.

The cold pressor test: vascular and myocardial response patterns and their stability.

The purposes of the present study were to compare the cardiovascular response patterns evoked by three versions of the cold pressor test (either forehead stimulation or hand or foot immersion) and to determine the reproducibility of the responses over a 2-week interval. Blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, and systolic time intervals were obtained during rest and during the cold pressor test in 42 young men. Across conditions, the pressor response was supported by peripheral resistance increases with concomitant stroke volume decreases. Although the response patterns were generally similar across sites, exceptions were apparent for heart rate. Forehead stimulation was characterized by no significant change in heart rate, whereas limb (hand or foot) immersion was associated with significant heart rate acceleration. The responses elicited by the three cold pressor test conditions were reliable and showed little evidence of attenuation over the test-retest interval.

The stability of cardiovascular parameters under different behavioral challenges: one-year follow-up.

The stability of myocardial, peripheral vascular and systolic time-interval measures was assessed over a one-year period in a sample of ten healthy normotensive men. Subjects participated in three laboratory sessions, the first two of which were two weeks apart, and the third approximately one year later. Measures were sampled during the preparation and delivery of a speech, a mirror star tracing task, and the forehead cold pressor test. The results of intraclass correlations computed between the mean of the first two sessions and the third showed that baseline and task levels were highly reproducible across all tasks and most parameters over the one year interval. Results also showed that the long term stability of delta is largely task-dependent.

Patterns and stability of cardiovascular responses to variations of the cold pressor test.

Test-retest reliabilities and patterns of heart rate and blood pressure responses were examined using variations in the cold pressor test in 113 normotensive white college men. Comparisons were made of stimulus site (forehead vs. foot) and bodily posture (seated vs. supine) across four separate groups of men. The stability of cardiovascular responses was examined over a 2-week-test-retest interval. Different cardiovascular response patterns emerged as a function of stimulation site and posture. Systolic and diastolic blood pressure increases were accompanied by bradycardia in the forehead cold pressor task but by tachycardia in the foot cold pressor task. Systolic blood pressure increases were larger for foot than for forehead stimulation. Heart rate increases were larger for supine than for seated men. Effects on response were independent of postural differences at baseline, and there were no stimulation site by posture interactions. The cardiovascular responses to stimulation did not attenuate across sessions in any experimental condition but were more reliable for foot than for forehead stimulation and for supine than for seated posture. Short-term stability for changes to the task approached that for baseline and task and was higher than has been reported elsewhere.

Myocardial and peripheral vascular responses to behavioral challenges and their stability in black and white Americans.

The purpose of this study was to assess the short term stability of myocardial and peripheral vascular responses to behavioral challenges, and to compare the response patterns of Black and White men. Blood pressure and heart rate, as well as stroke volume, cardiac output, total peripheral resistance, and systolic time interval measures derived from the impedance cardiogram were obtained in 12 Black and 12 White men. These measures were taken prior to and during an evaluative speech stressor, a mirror star tracing task, and a forehead cold pressor test presented during two laboratory sessions scheduled two weeks apart. In general, total peripheral resistance and impedance-derived baseline measures showed acceptable reproducibility (G greater than .85). With a few exceptions, adequate reliability was also demonstrated for change (delta) scores. All tasks raised blood pressure responses above resting levels. Blacks demonstrated significantly greater increases in total peripheral resistance responses across tasks. Whites but not Blacks also revealed increases above baseline in cardiac output and contractility as estimated by the Heather Index. These findings are consistent with the view that Blacks show greater vascular responsiveness than Whites across a variety of tasks, but reveal less myocardial responsiveness.