Glucocorticoids and insulin resistance: old hormones, new targets

1999 ◽  
Vol 96 (5) ◽  
pp. 513-523 ◽  
Author(s):  
Robert C. ANDREWS ◽  
Brian R. WALKER

Insulin resistance has been proposed as a mediator of the association between risk factors for cardiovascular disease in the population. The clinical syndrome of glucocorticoid excess (Cushing's syndrome) is associated with glucose intolerance, obesity and hypertension. By opposing the actions of insulin, glucocorticoids could contribute to insulin resistance and its association with other cardiovascular risk factors. In this review, we describe briefly the known mechanisms of insulin resistance and highlight the potential mechanisms for the effect of glucocorticoids. We then discuss factors which modulate the influence of glucocorticoids on insulin sensitivity; this highlights a novel therapeutic strategy to manipulate glucocorticoid action which may prove to be a useful tool in treating subjects with insulin resistance. Finally, we describe evidence from human studies that glucocorticoids make an important contribution to the pathophysiology of insulin resistance in the population.

2006 ◽  
Vol 154 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Lenora M Camarate S M Leão ◽  
Mônica Peres C Duarte ◽  
Dalva Margareth B Silva ◽  
Paulo Roberto V Bahia ◽  
Cláudia Medina Coeli ◽  
...  

Background: There has been a growing interest in treating postmenopausal women with androgens. However, hyperandrogenemia in females has been associated with increased risk of cardiovascular disease. Objective: We aimed to assess the effects of androgen replacement on cardiovascular risk factors. Design: Thirty-seven postmenopausal women aged 42–62 years that had undergone hysterectomy were prospectively enrolled in a double-blind protocol to receive, for 12 months, percutaneous estradiol (E2) (1 mg/day) combined with either methyltestosterone (MT) (1.25 mg/day) or placebo. Methods: Along with treatment, we evaluated serum E2, testosterone, sex hormone-binding globulin (SHBG), free androgen index, lipids, fibrinogen, and C-reactive protein; glucose tolerance; insulin resistance; blood pressure; body-mass index; and visceral and subcutaneous abdominal fat mass as assessed by computed tomography. Results: A significant reduction in SHBG (P < 0.001) and increase in free testosterone index (P < 0.05; Repeated measures analysis of variance) were seen in the MT group. Total cholesterol, triglycerides, fibrinogen, and systolic and diastolic blood pressure were significantly lowered to a similar extent by both regimens, but high-density lipoprotein cholesterol decreased only in the androgen group. MT-treated women showed a modest rise in body weight and gained visceral fat mass relative to the other group (P < 0.05), but there were no significant detrimental effects on fasting insulin levels and insulin resistance. Conclusion: This study suggests that the combination of low-dose oral MT and percutaneous E2, for 1 year, does not result in expressive increase of cardiovascular risk factors. This regimen can be recommended for symptomatic postmenopausal women, although it seems prudent to perform baseline and follow-up lipid profile and assessment of body composition, especially in those at high risk of cardiovascular disease.


2002 ◽  
Vol 2 (1_suppl) ◽  
pp. S9-S11 ◽  
Author(s):  
Markku Laakso

Insulin resistance is characterised by a decreased rate of insulin-mediated glucose uptake and is associated with adverse changes in cardiovascular risk factors, such as high triglyceride levels, low levels of high-density lipoprotein cholesterol, raised blood pressure, obesity and increased levels of plasminogen activator inhibitor 1. The term `insulin resistance syndrome' (IRS) is used to describe the complex of factors associated with insulin resistance that is found in patients both with and without type 2 diabetes. Although the presence of insulin resistance syndrome is generally considered to be a risk factor for cardiovascular disease, there is a lack of definitive evidence for a causal link. Recently, however, a statistical method known as factor analysis has been applied to the cluster of cardiovascular risk factors associated with IRS. This has been able to show that the `insulin resistance factor' (high plasma insulin and glucose levels, body mass index, waist-to-hip ratio and triglyceride levels) predicted coronary heart disease events in elderly non-diabetic men as well as in patients with type 2 diabetes. Therefore, treatment of insulin resistance whether by pharmacological (eg. thiazolidinediones) or nonpharmacological means has the potential to offer both improvements in glycaemic control and in cardiovascular events.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2012 ◽  
Author(s):  
Ruirui Gao ◽  
Whitney Duff ◽  
Donna Chizen ◽  
Gordon A. Zello ◽  
Philip D. Chilibeck

We determined the effects of a low glycemic-index pulse-based diet (i.e., containing lentils, chick peas, beans, and split peas) compared to a typical hospital diet on insulin sensitivity assessed by the Matsuda index from the insulin and glucose response to a two-hour oral glucose tolerance test, insulin resistance assessed by the homeostatic model assessment of insulin resistance (HOMA-IR), bone resorption assessed by 24 h excretion of urinary n-telopeptides(Ntx) and cardiovascular risk factors (blood lipids, blood pressure, arterial stiffness and heart rate variability) during bed rest. Using a randomized, counter-balanced cross-over design with one-month washout, six healthy individuals (30 ± 12 years) consumed the diets during four days of bed rest. The Matsuda index, HOMA-IR, urinary Ntx and cardiovascular risk factors were determined at baseline and after the last day of bed rest. Compared to the typical hospital diet, the pulse-based diet improved the Matsuda index (indicating increased insulin sensitivity; baseline to post-bed rest: 6.54 ± 1.94 to 6.39 ± 2.71 hospital diet vs. 7.14 ± 2.36 to 8.75 ± 3.13 pulse-based diet; p = 0.017), decreased HOMA-IR (1.38 ± 0.54 to 1.37 ± 0.50 hospital diet vs. 1.48 ± 0.54 to 0.88 ± 0.37 pulse-based diet; p = 0.022), and attenuated the increase in Ntx (+89 ± 75% hospital diet vs. +33 ± 20% pulse-based diet; p = 0.035). No differences for changes in cardiovascular risk factors were found between the two diet conditions, with the exception of decreased diastolic blood pressure during day three of bed rest in the pulse-based versus hospital diet (61 ± 9 vs. 66 ± 7 mmHg; p = 0.03). A pulse-based diet was superior to a hospital diet for maintaining insulin sensitivity, preventing insulin resistance, attenuating bone resorption and decreasing diastolic blood pressure during four days of bed rest.


Open Medicine ◽  
2008 ◽  
Vol 3 (3) ◽  
pp. 257-270 ◽  
Author(s):  
Ioana Ilie ◽  
Carmen Pepene ◽  
Ileana Duncea ◽  
Razvan Ilie

AbstractPolycystic ovary syndrome (PCOS) is possibly the most common endocrinopathy of reproductive age, characterized by hyperandrogenism and oligomenorrhea. Additionally, approximately one-third to one-half of all women and adolescent girls with PCOS tend to fulfill many of the metabolic syndrome criteria, and many view PCOS as a premetabolic syndrome condition, predisposing to a high risk for cardiovascular disease. Endothelial dysfunction, impaired arterial structure, or proinflammatory markers are early features of atherosclerosis, and can be used as surrogate indicators of future coronary artery disease in women with PCOS. However, as the latest studies show, these symptoms are the result of deleterious effects that cardiovascular risk factors, in particular insulin resistance and obesity, produce on the vascular wall, rather than to the presence of PCOS per se. The relationship between hyperandrogenemia and the risk of cardiovascular disease is controversial and needs to be clarified. Further research is warranted to understand the pathogenesis of cardiovascular disease in PCOS, and to identify subtypes of PCOS in which the presence of cardiovascular risk factors may result in increased cardiovascular events, leading to high morbidity or mortality rates caused by cardiovascular disease.


2021 ◽  
Vol 22 (16) ◽  
pp. 9063
Author(s):  
Dorota Purzycka-Bohdan ◽  
Anna Kisielnicka ◽  
Michał Bohdan ◽  
Aneta Szczerkowska-Dobosz ◽  
Marta Sobalska-Kwapis ◽  
...  

Cardiovascular risk factors are one of the most common comorbidities in psoriasis. A higher prevalence of hypertension, insulin resistance and type 2 diabetes, dyslipidemia, obesity, metabolic syndrome, depression, as well as cardiovascular disease was confirmed in psoriatic patients in comparison to the general population. Data suggest that psoriasis and systemic inflammatory disorders may originate from the pleiotropic interactions with many genetic pathways. In this review, the authors present the current state of knowledge on the potential genetic links between psoriasis and cardiovascular risk factors. The understanding of the processes linking psoriasis with cardiovascular risk factors can lead to improvement of psoriasis management in the future.


2021 ◽  
pp. 1-13
Author(s):  
Elisabeth Maria van Zutphen ◽  
Judith Johanna Maria Rijnhart ◽  
Didericke Rhebergen ◽  
Majon Muller ◽  
Martijn Huisman ◽  
...  

Background: Sex differences in cognitive functioning in old age are known to exist yet are still poorly understood. Objective: This study examines to what extent differences in cardiovascular risk factors and cardiovascular disease between men and women explain sex differences in cognitive functioning. Methods: Data from 2,724 older adults from the Longitudinal Aging Study Amsterdam were used. Information processing speed and episodic memory, measured three times during six years of follow-up, served as outcomes. The mediating role of cardiovascular risk factors and cardiovascular disease was examined in single and multiple mediator models. Determinant-mediator effects were estimated using linear or logistic regression, and determinant-outcome and mediator-outcome effects were estimated using linear mixed models. Indirect effects were estimated using the product-of-coefficients estimator. Results: Women scored 1.58 points higher on information processing speed and 1.53 points higher on episodic memory. Several cardiovascular risk factors had small mediating effects. The sex difference in information processing speed was mediated by smoking, depressive symptoms, obesity, and systolic blood pressure. The sex difference in episodic memory was mediated by smoking, physical activity, and depressive symptoms. Effects of smoking, LDL cholesterol, and diabetes mellitus on information processing speed differed between men and women. Conclusion: Differences in cardiovascular risk factors between women and men partially explained why women had better cognitive functioning. A healthy cardiovascular lifestyle seems beneficial for cognition and sex-specific strategies may be important to preserve cognitive functioning at older age.


Author(s):  
Eliana Portilla-Fernández ◽  
Shih-Jen Hwang ◽  
Rory Wilson ◽  
Jane Maddock ◽  
W. David Hill ◽  
...  

AbstractCommon carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = −0.0264, p value = 3.5 × 10–8) in the discovery panel and was replicated in replication panel (beta = −0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.


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