scholarly journals Novel metabolomic profile of subjects with non-classic apparent mineralocorticoid excess

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alejandra Tapia-Castillo ◽  
Cristian A. Carvajal ◽  
Xaviera López-Cortés ◽  
Andrea Vecchiola ◽  
Carlos E. Fardella

AbstractNonclassic apparent mineralocorticoid excess (NC-AME) is proposed as a novel clinical condition with a mild phenotypic spectrum that ranges from normotension to severe hypertension. This condition is mainly characterized by a high serum cortisol to cortisone ratio (F/E) and concomitant low cortisone (E), however further metabolic changes in NC-AME have not been studied. A cross-sectional study was performed in a primary-care cohort of 396 Chilean subjects, which were classified in two groups: NC-AME (n = 28) and healthy controls (n = 27). A discovery study based in untargeted metabolomics assay in serum samples from both groups was performed by UPLC-Q-TOF/MS. Global metabolomic variations were assayed by principal component analysis and further compared by orthogonal partial least-squares discriminant analysis (OPLS-DA). NC-AME subjects exhibited higher values of blood pressure, fractional excretion of potassium, and lower plasma renin activity and urinary sodium to potassium ratio. Metabolomic analyses showed 36 differentially regulated metabolites between NC-AME and control subjects. A ROC curve analyses identified eight metabolites with high discriminatory capacity between NC-AME and control subjects. Moreover, gamma-l-glutamyl-l-methionine sulfoxide and 5-sulfoxymethylfurfural, exhibited significant association with cortisone, which are potential biomarkers of NC-AME, however further assays should elucidate its biological role in setup and progression of this phenotype.

2020 ◽  
Author(s):  
Alejandra Tapia-Castillo ◽  
Cristian Carvajal ◽  
Andrea Vecchiola ◽  
Carlos Fardella

Abstract Nonclassic apparent mineralocorticoid excess (NC-AME) is proposed as a novel clinical condition with a mild phenotypic spectrum that ranges from normotension to severe hypertension. This condition is mainly characterized by a high serum cortisol to cortisone ratio (F/E) and concomitant low cortisone (E), however further metabolic changes in NC-AME have not been studied. A cross-sectional study was performed in a primary-care cohort of 396 Chilean subjects, which were classified in two groups: NC-AME (n=28) and healthy controls (n=27). An untargeted metabolomics assay in serum samples from both groups was performed by UPLC-Q-TOF/MS. Global metabolic variations were assayed by principal component analysis (PCA) and further compared by orthogonal partial least-squares discriminant analysis (OPLS-DA). NC-AME subjects exhibited higher values of blood pressure, fractional excretion of potassium, and lower plasma renin activity and urinary sodium to potassium ratio. Metabolomic analyses showed 36 differentially regulated metabolites between NC-AME and control subjects. The ROC curve analyses identified eight metabolites with high discriminatory capacity between NC-AME and control subjects. Moreover, gamma-L-glutamyl-L-methionine sulfoxide and 5-sulfoxymethylfurfural (SMF), exhibited significant association with cortisone, which are potential biomarkers of NCAME, however further assays should elucidate its biological role in setup and progression of this phenotype.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Alejandra Tapia-Castillo ◽  
Dominic Guanzon ◽  
Carlos Palma ◽  
Andrew Lai ◽  
Eric Barros ◽  
...  

Abstract Background The “nonclassic” apparent mineralocorticoid excess (NC-AME) has been identified in approximately 7% of general population. This phenotype is characterized by low plasma renin activity (PRA), high serum cortisol (F) to cortisone (E) ratio, low cortisone, high Fractional Excretion of potassium (FEK) and normal-elevated systolic blood pressure (SBP). An early detection and/or identification of novel biomarkers of this phenotype could avoid the progression or future complications leading to arterial hypertension. Isolation of extracellular vesicles, such as exosomes, in specific biofluids support the identification of tissue-specific RNA and miRNA, which may be useful as novel biomarkers. Our aim was to identify miRNAs within urinary exosomes associated to the NC-AME phenotype. Methods We perform a cross-sectional study in a primary care cohort of 127 Chilean subjects. We measured BP, serum cortisol, cortisone, aldosterone, PRA. According to the previous reported, a subgroup of subjects was classified as NC-AME (n = 10). Urinary exosomes were isolated and miRNA cargo was sequenced by Illumina-NextSeq-500. Results We found that NC-AME subjects had lower cortisone (p < 0.0001), higher F/E ratio (p < 0.0001), lower serum potassium (p = 0.009) and higher FEK 24 h (p = 0.03) than controls. We found miR-204-5p (fold-change = 0.115; p 0.001) and miR-192-5p (fold-change = 0.246; p 0.03) are both significantly downregulated in NC-AME. miR-192-5p expression was correlated with PRA (r = 0.45; p 0.028) and miR-204-5p expression with SBP (r = − 0.48, p 0.027) and F/E ratio (r = − 0.48; p 0.026). Conclusions These findings could support a potential role of these miRNAs as regulators and novel biomarkers of the NC-AME phenotype.


1970 ◽  
Vol 18 (1) ◽  
pp. 5-9
Author(s):  
MA Rayhan Khandakar ◽  
M Suhrab Ali ◽  
M Obaidullah ◽  
Liaquat Ali

Malnutrition Related Diabetes Mellitus (MRDM), a separate clinical class of diabetes mellitus recognized by WHO Study Group on Diabetes Mellitus in 1985 exhibits peculiar metabolic characteristic of ketosis resistance. To explore the role of cortisol and growth hormone in the development of ketosis resistance, a cross sectional study was carried out involving 21 newly diagnosed MRDM patients, 19 NIDDM patients, and 16 age matched non-diabetic control at BIRDEM, Dhaka. MRDM patients presented with significantly lower Body Mass Index (P<0.001) and significantly higher level of serum glucose (P<0.001) in comparison to NIDDM and control subjects. The mean serum cortisol was significantly higher in MRDM and NIDDM subjects compared to that of control (P<0.05). Therefore, regarding cortisol, MRDM patients behave exactly like NIDDM patients The serum growth hormone levels were similar in MRDM, NIDDM and control subjects. So it can be suggested from the study that cortisol and growth hormone may not play any significant role in the development of ketosis resistance in MRDM patients.    doi: 10.3329/taj.v18i1.3295 TAJ 2005; 18(1): 5-9


2020 ◽  
Vol 105 (7) ◽  
pp. 2430-2441
Author(s):  
Åse Bjorvatn Sævik ◽  
Anna-Karin Åkerman ◽  
Paal Methlie ◽  
Marcus Quinkler ◽  
Anders Palmstrøm Jørgensen ◽  
...  

Abstract Context Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison disease (AAD) produce corticosteroids even years after diagnosis. Objective To determine frequencies and clinical features of residual corticosteroid production in patients with AAD. Design Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid (GC) production was defined as quantifiable serum cortisol and 11-deoxycortisol and residual mineralocorticoid (MC) production as quantifiable serum aldosterone and corticosterone after &gt; 18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography–tandem mass spectrometry. Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test. Results Fifty-eight (30.2%) of 192 patients had residual GC production, more common in men (n = 33; P &lt; 0.002) and in shorter disease duration (median 6 [0-44] vs 13 [0-53] years; P &lt; 0.001). Residual MC production was found in 26 (13.5%) patients and associated with shorter disease duration (median 5.5 [0.5-26.0] vs 13 [0-53] years; P &lt; 0.004), lower fludrocortisone replacement dosage (median 0.075 [0.050-0.120] vs 0.100 [0.028-0.300] mg; P &lt; 0.005), and higher plasma renin concentration (median 179 [22-915] vs 47.5 [0.6-658.0] mU/L; P &lt; 0.001). There was no significant association between residual production and frequency of adrenal crises or quality of life. None had a normal cosyntropin response, but peak cortisol strongly correlated with unstimulated cortisol (r = 0.989; P &lt; 0.001) and plasma adrenocorticotropic hormone (ACTH; r = –0.487; P &lt; 0.001). Conclusion In established AAD, one-third of the patients still produce GCs even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life.


Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 658
Author(s):  
Federico Corvi ◽  
Federico Zicarelli ◽  
Matteo Airaldi ◽  
Salvatore Parrulli ◽  
Mariano Cozzi ◽  
...  

Background: To compare four different optical coherence tomography (OCT) devices for visualization of retinal and subretinal layers in highly myopic eyes. Methods: In this prospective, observational, cross-sectional study, consecutive patients with high myopia and control subjects were imaged by four OCT devices: Spectralis OCT2, PlexElite 2.0 100 kHz, PlexElite 2.0 200 kHz and the Canon Xephilio OCT-S1. The acquisition protocol for comparison consisted of single vertical and horizontal line scans centered on the fovea. Comparison between the devices in the extent of visible retina, presence of conjugate image or mirror artifacts, visibility of the sclerochoroidal interface and retrobulbar tissue. Results: 30 eyes with high myopia and 30 control subjects were analyzed. The visualized RPE length was significantly different between the OCT devices with Xephilio OCT-S1 imaging the largest extent (p < 0.0001). The proportion of eyes with conjugate image artifact was significantly higher with the Spectralis OCT (p < 0.0001), and lower with the PlexElite 200 kHz (p < 0.0001). No difference in visibility of the sclerochoroidal interface was noted among instruments. The retrobulbar tissue was visible in a higher proportion of eyes using swept-source PlexElite 100 kHz and 200 kHz (p < 0.007) compared to the other devices. Conclusions: In highly myopic eyes, the four OCT devices demonstrated significant differences in the extent of the retina imaged, in the prevalence of conjugate image artifact, and in the visualization of the retrobulbar tissue.


2018 ◽  
Vol 20 (5) ◽  
pp. 531-540 ◽  
Author(s):  
Paule V. Joseph ◽  
Hannah R. Davidson ◽  
Christina M. Boulineaux ◽  
Nicolaas H. Fourie ◽  
Alexis T. Franks ◽  
...  

The purpose of the study was to examine the interrelationships among stress, eating behavior, and adiposity in a cohort of normal- and overweight individuals. Clinical markers of physiological stress (fasting serum cortisol) and adiposity (body mass index [BMI] and percent body fat) were obtained from participants selected for a natural history protocol ( n = 107). Self-reported data on eating behavior (using the Three-Factor Eating Questionnaire subscales such as Cognitive Restraint, Disinhibition, and Hunger) and psychological stress (via the Perceived Stress Scale) were evaluated. Demographic information was incorporated using principal component analysis, which revealed sex- and weight-based differences in stress, adiposity, and eating behavior measures. Following a cross-sectional and descriptive analysis, significant correlations were found between the Disinhibition and Hunger eating behavior subscales and measures of adiposity including BMI ( r = .30, p = .002 and r = .20, p = .036, respectively) and percent body fat ( r = .43, p = .000 and r = .22, p = .022, respectively). Relationships between stress measures and eating behavior were also evident in the analysis. Disinhibition and Hunger correlated positively with perceived stress ( r = .32, p .001 and r = .26, p = .008, respectively). However, Disinhibition varied inversely with serum cortisol levels ( r = −.25, p = .009). Future studies are warranted to better understand this paradox underlying the effects of perceived and physiological stress on eating behavior.


SLEEP ◽  
1992 ◽  
Vol 15 (5) ◽  
pp. 423-429 ◽  
Author(s):  
H. Schulz ◽  
G. Brandenberger ◽  
S. Gudewill ◽  
D. Hasse ◽  
E. Kiss ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Laura Bordoni ◽  
Joanna J. Samulak ◽  
Angelika K. Sawicka ◽  
Iwona Pelikant-Malecka ◽  
Adrianna Radulska ◽  
...  

Abstract The early atherosclerotic lesions develop by the accumulation of arterial foam cells derived mainly from cholesterol-loaded macrophages. Therefore, cholesterol and cholesteryl ester transfer protein (CETP) have been considered as causative in atherosclerosis. Moreover, recent studies indicate the role of trimethylamine N-oxide (TMAO) in development of cardiovascular disease (CVD). The current study aimed to investigate the association between TMAO and CETP polymorphisms (rs12720922 and rs247616), previously identified as a genetic determinant of circulating CETP, in a population of coronary artery disease (CAD) patients (n = 394) and control subjects (n = 153). We also considered age, sex, trimethylamine (TMA) levels and glomerular filtration rate (GFR) as other factors that can potentially play a role in this complex picture. We found no association of TMAO with genetically determined CETP in a population of CAD patients and control subjects. Moreover, we noticed no differences between CAD patients and control subjects in plasma TMAO levels. On the contrary, lower levels of TMA in CAD patients respect to controls were observed. Our results indicated a significant correlation between GFR and TMAO, but not TMA. The debate whether TMAO can be a harmful, diagnostic or protective marker in CVD needs to be continued.


1995 ◽  
Vol 41 (12) ◽  
pp. 1844-1847 ◽  
Author(s):  
R Partanen ◽  
H Koskinen ◽  
P Oksa ◽  
K Hemminki ◽  
W Carney ◽  
...  

Abstract Using ELISAs, we determined the concentrations of transforming growth factor alpha (TGF-alpha), the extracellular domain of the erbB-2 receptor (erbB-2 ECD), and mutant p53 protein in stored serum samples of asbestosis patients with and without cancer and control subjects (without asbestosis or cancer). The percentage of individuals in these three groups with increased serum concentrations of TGF-alpha, erbB-2 ECD, and mutant p53, respectively, were: asbestosis patients with cancer, 36%, 16%, 19%; asbestosis patients without cancer, 38%, 19%, 6%; control subjects, 0%, 5%, 10%. Although differences in serum positivity for these oncoproteins were apparent among these groups, the differences did not achieve statistical significance (P &gt; 0.05). In several of the cancer cases, increased concentrations of TGF-alpha, erbB-2 ECD, and mutant p53 were also detected in the stored serum samples collected years before the clinical diagnosis of disease.


2021 ◽  
Author(s):  
Sergey Alekseevich Maksimov ◽  
Yulia A. Balanova ◽  
Svetlana A. Shalnova ◽  
Galina A. Muromtseva ◽  
Anna V. Kapustina ◽  
...  

Abstract Background. The objective of this study was to analyze the influence of the living characteristics of large regions on the possible presence, awareness, management and control of hypertension at the individual level in the Russian population.Methods. Regional characteristics were obtained from the official website of the Federal State Statistics Service of Russia. Principal component analysis was used to reduce the dimensionality of data; it allowed defining 5 integral regional indices: Socio-Geographical, Demographic, Industrial, Mixed, Economic. Presence, awareness, management and control of hypertension were assessed according to the data of the cross-sectional stage of ESSE-RF study that was conducted in 2013-2014. The final sample included 19,791 patients from 12 regions of Russia. Generalized estimation equations were used to determine associations between regional indices and presence, awareness, management and control of hypertension at the individual level taking into consideration nested data structures (individuals in regions).Results. The Socio-Geographic Index demonstrated the positive impact on hypertension among male (OR = 1.18; 95% CI: 1.05-1.32), undereducated individuals (OR = 1.14; 95% CI: 1.02-1.27) and elderly people (OR = 1.16; 95% CI: 1.02-1.32). Awareness of hypertension is positively associated with Demographic (OR = 1.13; 95% CI: 1.02-1.25) and Industrial Indices (OR = 1.15; 95% CI: 1.01-1.33). Worsening of social environment (Socio-Geographic Index) reduces adherence to management (OR = 0.76; 95% CI: 0.64-0.90) and control of hypertension (OR = 0.79; 95% CI: 0.69-0.90). Impact of regional living conditions on the prevalence of hypertension is not high, compared to the individual predictors, but for the awareness, treatment and control of hypertension, this influence is important.Conclusions: The study performed allowed assessing the influence of living characteristics of the population in the large regions of Russia on the prevalence of hypertension and on the awareness, management and control of this disease. The data obtained provide new knowledge not only in terms of epidemiology of cardiovascular diseases in Russia but also in general, that is, in the context of studying the influence of living conditions on the health of population.


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