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Chronic stress and insulin-resistance-related indices of cardiovascular disease risk. Part I. Neurophysiological responses and pathological sequelae

August 2007
Alternative Therapies in Health and Medicine 13(4)

Authors:

Heather Vincent

University of Florida

Kim Elizabeth Innes

West Virginia University School of Public Health, Dept Epidemiology

Ann Gill Taylor

University of Virginia

Cardiovascular disease (CVD) is the leading cause of death and disability in the industrialized world, and the prevalence is increasing rapidly among developing nations. The rising prevalence of CVD worldwide may be attributed in large part to specific atherogenic changes in insulin resistance, adiposity, lipid profiles, and other indices of insulin resistance syndrome (IRS), a cluster of metabolic and hemodynamic abnormalities that are strongly predictive of CVD. A growing body of research suggests that chronic psychosocial stress and related factors significantly contribute to the pathogenesis of IRS-related abnormalities, associated insulin-resistant states, and CVD, in part by promoting dysregulation of the sympathoadrenal system and hypothalamic-pituitary-adrenal axis. In this article, we review the literature supporting the relationships between these factors, outline the neurophysiologic responses to chronic stress, and discuss the pathways by which chronic or recurrent psychosocial stress may lead to a destructive cascade of neuroendocrine, metabolic, inflammatory, and neuropsychological changes that fosters the development of IRS and, ultimately, CVD.

FIGURE Pathological Sequelae of Chronic Stress CVD=cardiovascular disease; HPA=hypothalamic-pituitary-adrenal; HRV=heart rate variability; IGF-1=insulin-like growth factor-1; IRS=insulin resistance syndrome; SNS=sympathetic nervous system

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Dissertation: The influence of stressful life events on the development of type 2 diabetes

Thesis

Full-text available

May 2019

Joshua Minks

This study examined the relationship between distress and the development of Type 2 diabetes mellitus (T2DM) in the presence of established risk factors. Distress secondary to mental health disparities, stressful life events, and work conditions has been shown to promote insulin resistance and the development of T2DM. Subjects (N=79) diagnosed with T2DM within the previous six months were recruited from SSM Health Centers and VA Medical Centers in the greater St. Louis area. They completed the Recent Life Changes Questionnaire, ENRICHD Social Support Instrument, and a demographic survey and analyses were conducted to determine differences between the veteran and non-veteran subsamples, as well as determine the influence of distress and social support in the presence the established risk factors of age, BMI, and genetic risk for diabetes. The average subject's hemoglobin A1c (HbA1c) was 8.3%, BMI was 34.1, ESSI score was 15, and RLCQ score was 297.6 LCU. Twenty-nine subjects were diagnosed with a mental illness. Age and BMI had significant influence on the development of T2DM for the sample (β=-.241, p=.031 and β=-.293, p=0.10, respectively) while distress was not significant (β=-.040, p=.721). The mean HbA1c for the subgroups were significantly different (t=2.768, p=.007) The differences in age, BMI (t=-1.158, p=.250), GRD (t=-1.279, p=.206), and RLCQ scores (t=-.487, p=.628) were not significantly different.

Effects of Diaphragmatic Breathing and Systematic Relaxation on Depression, Anxiety, Stress, and Glycemic Control in Type 2 Diabetes Mellitus

Article

Sep 2021

This prospective study assessed the effects of diaphragmatic breathing and systematic relaxation on depression, anxiety, and stress levels, as well as glycemic control, in patients with type 2 diabetes mellitus (T2DM). One hundred patients with T2DM were randomly assigned to two equal groups: Group A patients received conventional treatment for T2DM, and Group B patients received conventional treatment for T2DM plus training in diaphragmatic breathing and systematic relaxation and home practice of these stress-management techniques for 6 months. Stress, depression, and anxiety levels, blood sugar, and glycated hemoglobin (HbA1c) were recorded at baseline and after 6 months of treatment in all patients. Baseline characteristics were compared using the chi-square test and student’s t test. Changes in mental well-being and glycemic status were assessed for their significance in each group using student’s t test and compared between two groups using one-way analysis of covariance (ANCOVA). Baseline levels of the respective change outcome and duration of diabetes were used as covariates in the ANCOVA. A significant decrease was seen in depression, anxiety, and stress scores in Group B, but in Group A only the stress score decreased after 6 months. A significant decline occurred in blood sugar (fasting, 2-hour postprandial, and random) and HbA1c in both groups after 6 months. There was a larger decrease in depression and anxiety scores and HbA1c in Group B than in Group A. The decrease in HbA1c was significantly correlated with the decrease in anxiety and stress scores in both groups and with the depression score in Group A. Thus, the addition of diaphragmatic breathing and systematic relaxation to conventional T2DM treatment appears to have led to improvement in mental well-being and glycemic control in patients with T2DM.

Hindbrain Adrenergic/Noradrenergic Control of Integrated Endocrine and Autonomic Stress Responses

Article

Nov 2023
ENDOCRINOLOGY

Hindbrain adrenergic/noradrenergic nuclei facilitate endocrine and autonomic responses to physical and psychological challenges. Neurons that synthesize adrenaline and noradrenaline target hypothalamic structures to modulate endocrine responses while descending spinal projections regulate sympathetic function. Furthermore, these neurons respond to diverse stress-related metabolic, autonomic, and psychosocial challenges. Accordingly, adrenergic and noradrenergic nuclei are integrative hubs that promote physiological adaptation to maintain homeostasis. However, the precise mechanisms through which adrenaline- and noradrenaline-synthesizing neurons sense interoceptive and exteroceptive cues to coordinate physiological responses have yet to be fully elucidated. Additionally, the regulatory role of these cells in the context of chronic stress has received limited attention. This mini-review consolidates reports from preclinical rodent studies on the organization and function of brainstem adrenaline and noradrenaline cells to provide a framework for how these nuclei coordinate endocrine and autonomic physiology. This includes identification of hindbrain adrenaline- and noradrenaline-producing cell groups and their role in stress responding through neurosecretory and autonomic engagement. Although temporally and mechanistically distinct, the endocrine and autonomic stress axes are complementary and interconnected. Therefore, the interplay between brainstem adrenergic/noradrenergic nuclei and peripheral physiological systems is necessary for integrated stress responses and organismal survival.

Racial, ethnic and nativity inequalities in gestational diabetes mellitus: The role of racial discrimination

Article

Full-text available

Jul 2022

Introduction Racial/ethnic minority and foreign-born women in the United States are at high risk of experiencing racial discrimination, which is associated with adverse health outcomes. Although racial discrimination is associated with metabolic disturbances such as insulin resistance and type 2 diabetes, more studies should examine its effect on gestational diabetes mellitus (GDM), which is highest among racial/ethnic minority and foreign-born women. Methods We used New York City Pregnancy Risk and Assessment Monitoring System survey data (2012–2014) linked with birth certificate items (N = 4084) in bivariate and multivariate analyses to examine racial/ethnic/nativity differences in racial discrimination, and to test if racial discrimination explains racial/ethnic/nativity inequalities in GDM. Results The 12-month prevalence of racial discrimination (9.5%) varied across race/ethnicity and nativity status, with Black, Hispanic and foreign-born women having the highest prevalence. Interaction effects indicate that US-born Black and Hispanic women are at increased risk of racial discrimination compared to their foreign-born counterparts. Women with GDM had statistically higher prevalence of racial discrimination (14%) compared with women without GDM (9%). Racial discrimination was associated with a 57% increased unadjusted risk of GDM (RR = 1.57, 95% CI [1.19, 2.06]) that decreased to 24% after adjusting for all covariates (RR = 1.24, 95% CI [0.87, 1.78]). Discussion The high proportion of racial/ethnic minority and foreign-born women experiencing racial discrimination, and its potential impact on GDM, underscores the importance of culturally informed screening and intervention approaches by trained professionals.

Sheetali Pranayama practice on cognition in patients with hypertension: a randomized controlled study

Article

Full-text available

Jan 2021

Prevalence of Contributing Factors Leading to the Development of Insulin Resistance Among Male Medical Students at a Private College in Saudi Arabia

Article

Full-text available

Nov 2023

Background Insulin resistance can result from various genetic and lifestyle factors. Initially, symptoms of insulin resistance may not be readily noticeable, but as the condition progresses, individuals may start experiencing symptoms. This study aimed to investigate the factors contributing to the development of insulin resistance among medical students at a private college in Saudi Arabia. Methodology We conducted a cross-sectional study using a convenient non-probability sampling technique, with a sample size of 241 participants. We employed validated questionnaires to gather information on physical activity, sleep, dietary habits, and stress. Specifically, we used the International Physical Activity Questionnaire (IPAQ)-Short Form for assessing physical activity, the Single-Item Sleep Quality Scale (SQS) for evaluating sleep quality, the Healthy Eating Quiz (HEQ) to gauge dietary patterns, and the stress questionnaire designed by the International Stress Management Association (ISMA) to measure stress levels. Additionally, we collected anthropometric measurements, as well as systolic and diastolic blood pressure readings. We calculated prevalence using percentages and employed the chi-square test to analyze variables, with a significance level set at p-values <0.05. Results This study investigated risk factors associated with lifestyle, focusing on waist circumference as an indicator of insulin resistance. Our findings revealed that a majority of individuals with high waist circumference were physically inactive and more susceptible to stress, and this difference was statistically significant when compared to those with normal waist circumference. Additionally, we observed that sleep deprivation and poor nutrition were more prevalent among individuals with high waist circumference, although these differences were not statistically significant. Conclusions This study highlights a high prevalence of elevated waist circumference, indicating insulin resistance, among medical students. Furthermore, it underscores the significant presence of well-known risk factors associated with insulin resistance within this population of medical students.

Racial/Ethnic and Nativity Inequalities in Gestational Diabetes Mellitus: The Role of Psychosocial Stressors

Article

Aug 2023
WOMEN HEALTH ISS

Introduction: Racial/ethnic and nativity disparities in gestational diabetes mellitus (GDM) persist in the United States. Identified factors associated with these differences do not fully explain them. Research has recognized psychosocial stress as a potentially modifiable risk factor for GDM. Methods: We used New York City Pregnancy Risk and Assessment Monitoring System data (2009-2014) linked with birth certificate items (n = 7,632) in bivariate and multivariate analyses to examine associations between 12 psychosocial stressors (modeled three ways: individual stressors, grouped stressors, stress constructs) and GDM across race/ethnicity and nativity, and if stressors explain racial/ethnic/nativity differences in GDM. Results: U.S. and foreign-born Black and Hispanic women reported higher stressors relative to U.S.-born White women. In fully adjusted models, the financial stress construct was associated with a 51% increased adjusted risk of GDM, and adding all stressors doubled the risk. Psychosocial stressors did not explain the elevated risk of GDM among foreign-born Black (adjusted risk ratio, 2.18; 95% confidence interval, 1.53-3.11), Hispanic (adjusted risk ratio, 1.57; 95% confidence interval, 1.10-2.25), or Asian/Pacific Islander (adjusted risk ratio, 4.10; 95% confidence interval, 3.04-5.52) women compared with U.S.-born White women. Conclusions: Historically minoritized racial/ethnic and immigrant women have an increased risk of psychosocial stressors and GDM relative to U.S.-born White women. Although financial and all stressors predicted higher risk of GDM, they did not explain the increased risk of GDM among immigrant and minoritized racial/ethnic women. Further examination into racial/ethnic and nativity inequalities in stress exposure and rates of GDM is warranted to promote healthier pregnancies and birth outcomes.

Evaluation of an association between maternal prenatal psychological stress and insulin resistance during pregnancy and postpartum

Article

Jul 2023
Indian J Physiol Pharmacol

Objectives Various physiological mechanisms counteract insulin resistance (IR) during normal pregnancy. Psychological stress is a known, independent risk factor for developing IR. Pregnancy-specific psychological stress may cause IR and increase the risk of overt diabetes. Hence, the study aims to evaluate maternal psychological stress using multiple stress markers and their association with changes in IR during pregnancy and postpartum. Materials and Methods Anthropometric measurements such as height, weight and skinfold thickness were measured using standard techniques. The stress markers were assessed using perceived stress scales (K10 questionnaire), a physiological marker of stress (Heart rate variability [HRV] measures) and biochemical stress markers (Saliva, hair cortisol levels). IR was estimated using homeostasis model assessment-estimated IR (HOMA-IR). The association of stress markers with IR was studied among fifty healthy pregnant women during pregnancy and postpartum. Results The psychological stress scores and saliva cortisol were significantly higher during pregnancy than postpartum ( P = 0.000). A comparison of cardiac autonomic function as assessed by HRV measures shows that high frequency in normalised units (HFnu) was significantly higher during the postnatal period than in the prenatal period ( P = 0.000). High frequency (HF) spectral power in absolute units was also significantly higher ( P = 0.002) in the postpartum period (2612.30 ± 432.24) when compared with the prenatal period (1446.10 ± 299.15). Low frequency in normalised units (LFnu), low frequency (LF)/HF ratio was significantly higher during the prenatal period than in the postnatal period ( P = 0.000). As assessed by HOMA-IR values, IR was significantly higher during the prenatal period than postpartum ( P = 0.04). There was a significant positive correlation between prenatal psychological stress scores, HRV parameters (LFnu, LF/HF) and postnatal IR. Conclusion Pregnancy is associated with higher psychological stress levels and IR than postpartum. Furthermore, the maternal cardiac autonomic marker could predict postnatal IR among healthy pregnant women.

Time-of-Day-Dependent Effects of Bromocriptine to Ameliorate Vascular Pathology and Metabolic Syndrome in SHR Rats Held on High Fat Diet

Article

Full-text available

Jun 2021
INT J MOL SCI

The treatment of type 2 diabetes patients with bromocriptine-QR, a unique, quick release micronized formulation of bromocriptine, improves glycemic control and reduces adverse cardiovascular events. While the improvement of glycemic control is largely the result of improved postprandial hepatic glucose metabolism and insulin action, the mechanisms underlying the drug’s cardioprotective effects are less well defined. Bromocriptine is a sympatholytic dopamine agonist and reduces the elevated sympathetic tone, characteristic of metabolic syndrome and type 2 diabetes, which potentiates elevations of vascular oxidative/nitrosative stress, known to precipitate cardiovascular disease. Therefore, this study investigated the impact of bromocriptine treatment upon biomarkers of vascular oxidative/nitrosative stress (including the pro-oxidative/nitrosative stress enzymes of NADPH oxidase 4, inducible nitric oxide (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), the pro-inflammatory/pro-oxidative marker GTP cyclohydrolase 1 (GTPCH 1), and the pro-vascular health enzyme, soluble guanylate cyclase (sGC) as well as the plasma level of thiobarbituric acid reactive substances (TBARS), a circulating marker of systemic oxidative stress), in hypertensive SHR rats held on a high fat diet to induce metabolic syndrome. Inasmuch as the central nervous system (CNS) dopaminergic activities both regulate and are regulated by CNS circadian pacemaker circuitry, this study also investigated the time-of-day-dependent effects of bromocriptine treatment (10 mg/kg/day at either 13 or 19 h after the onset of light (at the natural waking time or late during the activity period, respectively) among animals held on 14 h daily photoperiods for 16 days upon such vascular biomarkers of vascular redox state, several metabolic syndrome parameters, and mediobasal hypothalamic (MBH) mRNA expression levels of neuropeptides neuropeptide Y (NPY) and agouti-related protein (AgRP) which regulate the peripheral fuel metabolism and of mRNA expression of other MBH glial and neuronal cell genes that support such metabolism regulating neurons in this model system. Such bromocriptine treatment at ZT 13 improved (reduced) biomarkers of vascular oxidative/nitrosative stress including plasma TBARS level, aortic NADPH oxidase 4, iNOS and GTPCH 1 levels, and improved other markers of coupled eNOS function, including increased sGC protein level, relative to controls. However, bromocriptine treatment at ZT 19 produced no improvement in either coupled eNOS function or sGC protein level. Moreover, such ZT 13 bromocriptine treatment reduced several metabolic syndrome parameters including fasting insulin and leptin levels, as well as elevated systolic and diastolic blood pressure, insulin resistance, body fat store levels and liver fat content, however, such effects of ZT 19 bromocriptine treatment were largely absent versus control. Finally, ZT 13 bromocriptine treatment reduced MBH NPY and AgRP mRNA levels and mRNA levels of several MBH glial cell/neuronal genes that code for neuronal support/plasticity proteins (suggesting a shift in neuronal structure/function to a new metabolic control state) while ZT 19 treatment reduced only AgRP, not NPY, and was with very little effect on such MBH glial cell genes expression. These findings indicate that circadian-timed bromocriptine administration at the natural circadian peak of CNS dopaminergic activity (that is diminished in insulin resistant states), but not outside this daily time window when such CNS dopaminergic activity is naturally low, produces widespread improvements in biomarkers of vascular oxidative stress that are associated with the amelioration of metabolic syndrome and reductions in MBH neuropeptides and gene expressions known to facilitate metabolic syndrome. These results of such circadian-timed bromocriptine treatment upon vascular pathology provide potential mechanisms for the observed marked reductions in adverse cardiovascular events with circadian-timed bromocriptine-QR therapy (similarly timed to the onset of daily waking as in this study) of type 2 diabetes subjects and warrant further investigations into related mechanisms and the potential application of such intervention to prediabetes and metabolic syndrome patients as well.

Effects of a 12-week yoga versus a 12-week educational film intervention on symptoms of restless legs syndrome and related outcomes: An exploratory randomized controlled trial

Article

Jan 2020

Study objectives: To assess the effects of a yoga versus educational film (EF) program on restless legs syndrome (RLS) symptoms and related outcomes in adults with RLS. Methods: Forty-one community-dwelling, ambulatory nonpregnant adults with moderate to severe RLS were randomized to a 12-week yoga (n = 19) or EF program (n = 22). In addition to attending classes, all participants completed practice/treatment logs. Yoga group participants were asked to practice at home 30 minutes per day on nonclass days; EF participants were instructed to record any RLS treatments used on their daily logs. Core outcomes assessed pretreatment and posttreatment were RLS symptoms and symptom severity (International RLS Study Group Scale (IRLS) and RLS ordinal scale), sleep quality, mood, perceived stress, and quality of life (QOL). Results: Thirty adults (13 yoga, 17 EF), aged 24 to 73 (mean = 50.4 ± 2.4 years), completed the 12-week study (78% female, 80.5% white). Post-intervention, both groups showed significant improvement in RLS symptoms and severity, perceived stress, mood, and QOL-mental health (P ≤ .04). Relative to the EF group, yoga participants demonstrated significantly greater reductions in RLS symptoms and symptom severity (P ≤ .01), and greater improvements in perceived stress and mood (P ≤ .04), as well as sleep quality (P = .09); RLS symptoms decreased to minimal/mild in 77% of yoga group participants, with none scoring in the severe range by week 12, versus 24% and 12%, respectively, in EF participants. In the yoga group, IRLS and RLS severity scores declined with increasing minutes of homework practice (r = .7, P = .009 and r = .6, P = .03, respectively), suggesting a possible dose-response relationship. Conclusions: Findings of this exploratory RCT suggest that yoga may be effective in reducing RLS symptoms and symptom severity, decreasing perceived stress, and improving mood and sleep in adults with RLS. Clinical trial registration: Registry: Clinicaltrials.gov; Title: Yoga vs. Education for Restless Legs: a Feasibility Study; Identifier: NCT03570515; URL: https://clinicaltrials.gov/ct2/show/NCT03570515.

Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine

Article

Full-text available

Feb 2016

Interaction of workplace demands and cardiovascular reactivity in progression of carotid atherosclerosis: Population based study

Article

Full-text available

Feb 1997

To examine the combined influence of workplace demands and changes in blood pressure induced by stress on the progression of carotid atherosclerosis. Population based follow up study of unestablished as well as traditional risk factors for carotid atherosclerosis, ischaemic heart disease, and other outcomes. Eastern Finland. 591 men aged 42-60 who were fully employed at baseline and had complete data on the measures of carotid atherosclerosis, job demands, blood pressure reactivity, and covariates. Change in ultrasonographically assessed intima-media thickness of the right and left common carotid arteries from baseline to 4 year follow up. Significant interactions between workplace demands and stress induced reactivity were observed for all measures of progression (P < 0.04). Men with large changes in systolic blood pressure (20 mm Hg or greater) in anticipation of a maximal exercise test and with high job demands had 10-40% greater progression of mean (0.138 v 0.123 mm) and maximum (0.320 v 0.261 mm) intima-media thickness and plaque height (0.347 v 0.264) than men who were less reactive and had fewer job demands. Similar results were obtained after excluding men with prevalent ischaemic heart disease at baseline. Findings were strongest among men with at least 20% stenosis or non-stenotic plaque at baseline. In this subgroup reactive men with high job demands had more than 46% greater atherosclerotic progression than the others. Adjustment for atherosclerotic risk factors did not alter the results. Men who showed stress induced blood pressure reactivity and who reported high job demands experienced the greatest atherosclerotic progression, showing the association between dispositional risk characteristics and contextual determinants of disease and suggesting that behaviourally evoked cardiovascular reactivity may have a role in atherogenesis.

Endocrine abnormalities in obesity

Article

Jan 1997

P. Bjorntorp

There are a multitude of endocrine abnormalities in human obesity. In this review, those of steroid hormones, growth hormone (GH), and insulin are considered. Characteristic of all these abnormalities is that they are more pronounced in obesity with central visceral preponderance than with peripheral gluteofemoral enlargement of adipose tissue depots. Cortisol secretion is frequently increased as a result of a hypersensitive hypothalamopituitary adrenal (HPA) axis. This may also be followed by increased adrenal androgen secretion in women. The HPA axis disturbance might be due to excess traffic over the axis and/or a downregulation of the feedback inhibition by central glucocorticoid receptors, with or without a genetic susceptibility. Probably secondarily the hypothalamopituitary-gonadal and GH axes are inhibited. The net result is increased cortisol, and, in women, androgen secretions, and inhibited gender-specific sex steroid hormones as well as GH. These hormonal abnormalities, in concert with elevated free fatty acid concentrations, probably contribute significantly to peripheral insulin resistance. Cortisol and insulin facilitate triglyceride accumulation, whereas sex steroids and GH both inhibit triglyceride accumulation as well as activate lipid mobilization pathways. The endocrine abnormalities in central, visceral obesity therefore seem to create a milieu for lipid accumulation in adipose tissue in general. This is probably more pronounced in visceral than in other adipose tissue depots because of the higher density of active cytoplasmic mass, elevated blood flow and dense innervation, as well as the higher density of specific steroid hormone receptors. Therefore, excess triglycerides probably tend to accumulate preferentially in visceral adipose tissue because of the combined endocrine abnormalities in central, visceral obesity, This conclusion is based on consistent data regarding cellular and molecular levels from in vivo studies of lipid uptake and mobilization in humans, as well as from clinical and intervention studies with in vitro measurements of metabolic pathways and the net effects on visceral adipose tissue mass. The effect of steroid hormones in women remains unclear.

Mechanisms of disease: Atherosclerosis - An inflammatory disease

Article

Jan 1999

R. Ross

IGF-I Treatment Reduces Hyperphagia, Obesity, and Hypertension in Metabolic Disorders Induced by Fetal Programming

Article

Sep 2001

Mark H Vickers

The discovery of a link between in utero experience and later metabolic and cardiovascular disease is one of the most important advances in epidemiology research of recent years. There is increasing evidence that alterations in the fetal environment may have long-term consequences on cardiovascular, metabolic, and endocrine pathophysiology in adult life. This process has been termed programming, and we have shown that undernutrition of the mother during gestation leads to programming of hyperphagia, obesity, hypertension, hyperinsulinemia, and hyperleptinemia in the offspring. Using this model of maternal undernutrition throughout pregnancy combined with postnatal hypercaloric nutrition of the offspring, we examined the effects of IGF-I therapy. Virgin Wistar rats (age 75 ± 5 d, n = 20 per group) were time mated and randomly assigned to receive food either ad libitum or 30% of ad libitum intake (UN) throughout pregnancy. At weaning, female offspring were assigned to one of two diets (control or hypercaloric[ 30% fat]). Systolic blood pressure was measured at day 175 and following infusion with 3 μg/g per day recombinant human IGF-1 (rh-IGF-I) by minipump for 14 d. Before treatment, UN offspring were hyperinsulinemic, hyperleptinemic, hyperphagic, obese, and hypertensive on both diets, compared with ad libitum offspring and this was exacerbated by hypercaloric nutrition. IGF-I treatment increased body weight in all treated animals. However, systolic blood pressure, food intake, retroperitoneal and gonadal fat pad weights, and plasma leptin and insulin concentrations were markedly reduced with IGF-I treatment. IGF-I treatment resulted in a 3- to 5-fold increase in 38–44 kDa and 28–30 kDa IGF binding proteins, although in UN animals, there was an impaired and differential up-regulation of these insulin-like growth factor binding proteins following IGF-I treatment. The 24-kDa IGF binding protein representing IGF binding protein-4 was down-regulated in all IGF-I-treated animals, but the decrease was more marked in UN animals. Our data suggest that IGF-I treatment alleviates hyperphagia, obesity, hyperinsulinemia, hyperleptinemia, and hypertension in rats programmed to develop the metabolic syndrome X.

Abdominal Fat and Sympathetic Overactivity

Article

Dec 2003

Background: Epidemiologic studies have found an association between overweight and increased mortality arising primarily from cardiovascular disorders. A major determinant is a chronically raised sympathetic nervous system activity which can arise from calorie intake-dependent and -independent mechanisms. Calorie-dependent parameters reflecting sympathetic overactivity are an increased body fat mass and body mass index. Visceral Fat: Although influenced by calorie intake to a certain extent, visceral fat accumulation is a mechanism which is determined also by estrogen deficiency (postmenopausal hypertension) or enhanced corticoid influences. It is hypothesized that excess catecholamines trigger various adverse processes which, if they persist, can lead or aggravate hypertension and insulin resistance. Visceral but not peripheral fat mass was correlated with atherogenic metabolites. Excess Catecholamine Syndrome: The present focus on visceral fat accumulation strengthens the concept of an “excess catecholamine syndrome” of which the ”metabolic syndrome” appears as one consequence. It is proposed to further assess the potential of transthoracic echocardiography as routine imaging method for the prediction of visceral fat accumulation and its adverse health consequences.

The Importance of Indirect Costs in Primary Cardiovascular Disease Prevention

Article

Feb 2003
ARCH INTERN MED

Background The losses in productivity due to cardiovascular disease (CVD) are substantial but rarely considered in health economic analyses. We compared the cost-effectiveness of lipid level modification in the primary prevention of CVD with and without these indirect costs. Methods We used the Cardiovascular Life Expectancy Model to estimate the long-term benefits and cost-effectiveness of lipid level modification with atorvastatin calcium, including 28% and 38% reductions in total cholesterol and low-density lipoprotein cholesterol levels, respectively, and a 5.5% increase in high-density lipoprotein cholesterol level. The direct costs included all medical care costs associated with CVD. The indirect costs represented the loss of employment income and the decreased value of housekeeping services after different manifestations of CVD. All costs were expressed in 2000 Canadian dollars. Results When only direct medical care costs were considered, the incremental cost-effectiveness ratios for lifelong therapy with atorvastatin calcium, 10 mg/d, were generally positive, ranging from a few thousand to nearly

20 000 per year of life saved. When the societal point of view was adopted and indirect costs were included, the total costs were generally negative, representing substantial cost savings (up to

50 000) and increased life expectancy for most groups of individuals. Conclusions Lipid therapy with statins can reduce CVD morbidity and mortality as demonstrated in a number of clinical trials. Adding the indirect CVD costs associated with productivity losses at work and home can result in forecasted cost savings to society as a whole such that lipid therapy could potentially save lives and money.

Sex Differences in Insulin Resistance and Cardiovascular Disease Risk

Article

Sep 2013
J CLIN ENDOCR METAB

Context: The possibility that differences in insulin sensitivity explain why women, especially younger women, have a lower cardiovascular disease (CVD) risk than men remains an unsettled issue. Objective: The objective of this study was to evaluate whether sex disparities in CVD risk are associated with differences in insulin resistance. Design/setting/participants: This was a cross-sectional study of women (n = 468) and men (n = 354) who had the measurement of CVD risk factors and steady-state plasma glucose (SSPG) concentration (insulin resistance) using the insulin suppression test. The population was also divided by median age (51 y) to evaluate the effect of age on sex differences. Main outcome measures/results: In general, the SSPG concentration was similar between sexes. At higher BMI (≥30 kg/m(2)), women had significantly lower SSPG concentration than men (sex × BMI interaction, P = .001). However, sex differences in CVD risk factors were not due to differences in SSPG but accentuated by a higher degree of insulin resistance in younger (age < 51 y) but not older (≥ 51 y) individuals. In younger individuals, women had significantly (P ≤ .007) lower diastolic blood pressure and fasting glucose and triglyceride concentration compared with men in SSPG tertile 3 (most insulin resistant) but not in tertile 1 (least insulin resistant). Older women had lower diastolic blood pressure compared with men, regardless of SSPG. High-density lipoprotein cholesterol remained higher in women, regardless of age or SSPG. Conclusions: The female advantage is not due to a difference in insulin action but results from an attenuation of the relationship between insulin resistance and CVD risk, especially in younger individuals.

Studies of hormone action in the hippocampal formation

Article

Oct 2002
J PSYCHOSOM RES

Objectives: The goal is to review the plasticity and vulnerability of the hippocampus, a brain structure involved in episodic, declarative, contextual and spatial learning and memory, as well as its being a component in the control of autonomic and vegetative functions such as ACTH secretion. It discusses its possible role in the regulation of glucose homeostasis, and the need of hippocampal neurons for glucose because of their high metabolic activity. The hippocampus is also vulnerable to damage by stroke and head trauma and susceptible to damage during aging and repeated stress, and is sensitive to the effects of diabetes. Methods: A summary of recent work in the author's laboratory and related work in the field using citations of literature based, in part, on Medline searches. Conclusions: In addition to its vulnerability, the hippocampus is also a plastic and adaptable brain region that is capable of considerable structural reorganization, including remodeling of dendrites and neurogenesis of dentate gyrus granule neurons in response to repeated stress. Animal models of Type 1 diabetes show accelerated remodeling of dendrites, and Type 2 diabetes remains to be studied in this regard. This is relevant to major depressive illness, in which a progressive atrophy of the hippocampal formation is reported and is accompanied by impairment of cognitive function in those subjects with hippocampal shrinkage. Therefore, hippocampal atrophy in depression, as well as in diabetes, may reflect either damage or plasticity involving structural reorganization that is potentially treatable.

Effect of Rosary Prayer and Yoga Mantras on Autonomic Cardiovascular Rhythms: Comparative Study

Article

Dec 2001

Objective: To test whether rhythmic formulas such as the rosary and yoga mantras can synchronise and reinforce inherent cardiovascular rhythms and modify baroreflex sensitivity. Design: Comparison of effects of recitation of the Ave Maria (in Latin) or of a mantra, during spontaneous and metronome controlled breathing, on breathing rate and on spontaneous oscillations in RR interval, and on blood pressure and cerebral circulation. Setting: Florence and Pavia, Italy. Participants: 23 healthy adults. Main outcome measures: Breathing rate, regularity of breathing, baroreflex sensitivity, frequency of cardiovascular oscillations. Results: Both prayer and mantra caused striking, powerful, and synchronous increases in existing cardiovascular rhythms when recited six times a minute. Baroreflex sensitivity also increased significantly, from 9.5 (SD 4.6) to 11.5 (4.9) ms/mm Hg, P<0.05. Conclusion: Rhythm formulas that involve breathing at six breaths per minute induce favourable psychological and possibly physiological effects. What is already known on this topic What is already known on this topic Reduced heart rate variability and baroreflex sensitivity are powerful and independent predictors of poor prognosis in heart disease Slow breathing enhances heart rate variability and baroreflex sensitivity by synchronising inherent cardiovascular rhythms