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Disruption of multisystem responses to stress in type 2 diabetes: investigating the dynamics of allostatic load.

ABSTRACT: Psychological stress-related processes are thought to contribute to the development and progression of type 2 diabetes, but the biological mechanisms involved are poorly understood. Here, we tested the notion that people with type 2 diabetes experience chronic allostatic load, manifest as dynamic disturbances in reactivity to and recovery from stress across multiple (cardiovascular, neuroendocrine, inflammatory, metabolic) biological systems, coupled with heightened experience of chronic life stress. We carried out an experimental comparison of 140 men and women aged 50-75 y with type 2 diabetes and 280 nondiabetic individuals matched on age, sex, and income. We monitored blood pressure (BP) and heart rate, salivary cortisol, plasma interleukin (IL)-6, and total cholesterol in response to standardized mental stress, and assessed salivary cortisol over the day. People with type 2 diabetes showed impaired poststress recovery in systolic and diastolic BP, heart rate and cholesterol, and blunted stress reactivity in systolic BP, cortisol, cholesterol, and IL-6. Cortisol and IL-6 concentrations were elevated, and cortisol measured over the day was higher in the type 2 diabetes group. Diabetic persons reported greater depressive and hostile symptoms and greater stress experience than did healthy controls. Type 2 diabetes is characterized by disruption of stress-related processes across multiple biological systems and increased exposure to life stress. Chronic allostatic load provides a unifying perspective with implications for etiology and patient management.

SUBMITTER: Steptoe A

PROVIDER: S-EPMC4226108 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Disruption of multisystem responses to stress in type 2 diabetes: investigating the dynamics of allostatic load.

Steptoe Andrew A Hackett Ruth A RA Lazzarino Antonio I AI Bostock Sophie S La Marca Roberto R Carvalho Livia A LA Hamer Mark M

Proceedings of the National Academy of Sciences of the United States of America 20141020 44

Psychological stress-related processes are thought to contribute to the development and progression of type 2 diabetes, but the biological mechanisms involved are poorly understood. Here, we tested the notion that people with type 2 diabetes experience chronic allostatic load, manifest as dynamic disturbances in reactivity to and recovery from stress across multiple (cardiovascular, neuroendocrine, inflammatory, metabolic) biological systems, coupled with heightened experience of chronic life st ...[more]

PMID: 25331894

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Project description:AimsAlcohol use is associated with both positive and negative effects on individual cardiovascular risk factors, depending upon which risk factor is assessed. The present analysis uses a summative multisystem index of biologic risk, known as allostatic load (AL), to evaluate whether the overall balance of alcohol-associated positive and negative cardiovascular risk factors may be favorable or unfavorable.MethodsThis analysis included 1255 adults from the Midlife in the United States (MIDUS) biomarker substudy. Participants, average age 54.5 (±11) years, were divided into 6 alcohol-use categories based on self-reported drinking habits. Current non-drinkers were classified as lifelong abstainers and former light drinkers, former moderate drinkers, or former heavy drinkers. Current alcohol users were classified as light, moderate, or heavy drinkers. A total AL score was calculated using 24 biomarkers grouped into 7 physiologic systems including cardiovascular, inflammation, glucose metabolism, lipid metabolism, sympathetic and parasympathetic nervous systems, and the hypothalamic-pituitary-adrenal axis. Mixed-effects regression models were fit to determine the relationship between alcohol use categories and AL with controls for covariates that may influence the relationship between alcohol use and AL.Results468 (37.6%) individuals were current non-drinkers while 776 (62.4%) were current drinkers. In adjusted mixed-effects regression models, all 3 groups of current drinkers had significantly lower average AL scores than the lifelong abstainer/former light drinker group (light: -0.23, 95% CI -0.40, -0.07, p < 0.01; moderate: -0.20, 95% CI -0.38, -0.02, p < 0.05; heavy: -0.30, 95% CI -0.57, -0.04, p < 0.05), while the average AL scores of former moderate and former heavy drinkers did not differ from the lifelong abstainer/former light drinker group.ConclusionsCurrent alcohol use is associated cross-sectionally with a favorable multisystem physiologic score known to be associated with better long-term health outcomes, providing evidence in support of long-term health benefits related to alcohol consumption.

Project description:BackgroundAfrican American (AA) women navigate the world with multiple intersecting marginalized identities. Accordingly, AA women have higher cumulative stress burden or allostatic load (AL) compared to other women. Studies suggest that AA women with a college degree or higher have lower AL than AA women with less than a high school diploma. We examined the joint effect of educational attainment and AL status with long-term risk of cancer mortality, and whether education moderated the association between AL and cancer mortality.MethodsWe performed a retrospective analysis among 4,677 AA women within the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2010 with follow-up data through December 31, 2019. We fit weighted Cox proportional hazards models to estimate adjusted hazard ratios (aHRs) of cancer death between educational attainment/AL (adjusted for age, income, and smoking status).ResultsAA women with less than a high school diploma living with high AL had nearly a 3-fold increased risk (unadjusted HR: 2.98; 95%C CI: 1.24-7.15) of cancer death compared to AA college graduates living with low AL. However, after adjusting for age, this effect attenuated (age-adjusted HR: 1.11; 95% CI: 0.45-2.74). AA women with high AL had 2.3-fold increased risk of cancer death (fully adjusted HR: 2.26; 95% CI: 1.10-4.57) when compared to AA with low AL, specifically among women with high school diploma or equivalent and without history of cancer.ConclusionsOur findings suggest that high allostatic load is associated with a higher risk of cancer mortality among AA women with lower educational attainment, while no such association was observed among AA women with higher educational attainment. Thus, educational attainment plays a modifying role in the relationship between allostatic load and the risk of cancer death for AA women. Higher education can bring several benefits, including improved access to medical care and enhanced medical literacy, which in turn may help mitigate the adverse impact of AL and the heightened risk of cancer mortality among AA women.

Project description:Background Prevention of hearing loss via addressing potentially modifiable risk factors may offer means of reducing the global burden of hearing loss. Prior studies reported associations between individual markers of inflammation and risk of hearing impairment. Allostatic load is an index of cumulative physiological stressors, including inflammation, to multiple biological systems. Our aims were to investigate associations between allostatic load and both audiometric and self-reported hearing impairment and examine whether associations are stronger over time due to prolonged high allostatic load. Methods Data were taken from the English Longitudinal Study of Ageing (ELSA), a nationally representative study of people aged 50+ living in England over 3 time points between 2008 and 2014. Allostatic load score was comprised of thirteen different measures available at baseline and 4 years post-baseline (high-density lipoprotein/total cholesterol, triglyceride, fibrinogen, haemoglobin A1c, C-reactive protein, insulin-like growth factor 1 (IGF-1), systolic and diastolic blood pressure, mean arterial pressure, resting pulse rate, peak expiratory flow, BMI and waist circumference), measured using clinical cut-off points for normal biomarker parameters. Hearing acuity was measured with a simple handheld tone-producing device at follow-up 7 years post-baseline, while self-reported hearing impairment was measured at time point. Results We included samples of 4373 and 4430 for the cross-sectional and longitudinal analysis, respectively. In the cross-sectional model high allostatic load was associated both self-reported (OR = 1.08, 95% CI 1.0,1.1; p < 0.01) and objective hearing loss (OR = 1.10, 95% CI 1.1,1.2; p < 0.001) adjusting for age and sex. Cross-sectional associations between allostatic load and hearing were not significant after further adjustment for covariates (qualification, physical activity and smoking). In longitudinal modelling, high allostatic load was associated with both audiometric (Z score OR = 1.11, 95% CI 1.1,1.2; p < 0.001) and self-reported hearing impairment (OR = 1.08, 95% CI 1.0,1.1; p < 0.001) adjusting for age and sex. Allostatic load was no longer associated with self-reported hearing loss but the association with audiometric hearing impairment (OR = 1.08, 95% CI 1.03,1.13; p < 0.001) remained following additional adjustment for baseline self-reported hearing, education, physical activity, and smoking. Conclusions Prolonged high allostatic load was associated with risk of hearing impairment. Reducing allostatic load via healthy lifestyle changes including non-smoking, healthy diet and exercise may offer an opportunity to reduce the risk of hearing impairment in later life. Highlights • Allostatic load captures cumulative physiological stress which has consequence for subsequent hearing function.• Prolonged high allostatic load was associated with risk of objectively measured hearing impairment.• This association is shown in nationally representative longitudinal ageing study.

Project description:Allostatic load is commonly operationalized using a sum-score of high-risk biomarkers. However, this method implies that biomarkers contribute equally to allostatic load, as each is given equal weight. Our goal in this methodological paper is to evaluate this, and complementarily, to identify biomarkers that are most informative and least informative for developing an allostatic load index. Item response theory models provide an alternate approach to calculating the allostatic load score, by treating individual biomarkers (e.g. “items”) as indicators of a latent allostatic load construct. Item response theory scores account for the data-driven discriminating power of each biomarker, and an individual’s pattern of biomarker responses. To demonstrate feasibility of this approach, we used data from the 2015–2016 National Health Examination and Nutrition Survey (NHANES; N = 3751), with twelve allostatic load biomarkers representing immune response, metabolic function and cardiovascular health. Item response theory models revealed that body-mass-index and C-reactive protein were the most informative biomarkers for allostatic load. Both higher allostatic load sum-score and allostatic load item response theory score were associated with lower socio-economic status (p = 0.008; p<0.001, respectively). Further, both formulations of allostatic load were positively associated with a nine-item depression screener (p<0.001 for both), but only the item response theory score was also positively associated with the impact of depressive symptoms on daily life (p = 0.045). Item response theory scores may be more finely tuned to tease out effects, compared to sum-scores, and also provide more flexibility when there are missing biomarker measurements. Supplemental R code for our approach are included. Highlights • Methodological paper to introduce item response theory for calculating allostatic load.• Biomarker data from NHANES 2015–2016 representative of United States adults.• Body-mass-index and C-reactive protein most informative for allostatic load.• Item response theory captures more variability in allostatic load compared to sum-scores.• Future work - item response theory can standardize allostatic load across datasets.

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Disruption of multisystem responses to stress in type 2 diabetes: investigating the dynamics of allostatic load.

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Disruption of multisystem responses to stress in type 2 diabetes: investigating the dynamics of allostatic load.

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