The Role of Morning Plasma Cortisol in Obesity: A Bi-directional Mendelian Randomization Study

2022 ◽  
Author(s):  
Xiaohui QI ◽  
Bin CUI ◽  
Min CAO
Keyword(s):  
Genetic Variants ◽  
Plasma Cortisol ◽  
Mendelian Randomization ◽  
Class Ii ◽  
Class I ◽  
Class Iii ◽  
Reverse Causality ◽  
Obese People ◽  
Obesity Class

Abstract Context Cortisol, an important hormone regulated by the hypothalamic-pituitary-adrenal (HPA) axis, is associated with obesity. However, it is unclear whether the relationship between cortisol and obesity is causal or could be explained by reverse causality. Objective This work aims to assess the role of morning plasma cortisol in clinical classes of obesity. Methods In this bi-directional two-sample Mendelian Randomization (MR) study, cortisol-associated genetic variants were obtained from the CORtisol NETwork consortium (n = 12,597). The primary outcomes were obesity class I (BMI ≥ 30 kg/m 2), class II (BMI ≥ 35 kg/m 2), and class III (BMI ≥ 40kg/m 2). Inverse variance weighting (IVW) method was used as the main analysis, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. Conversely, genetic variants predicting clinical classes of obesity were applied to the cortisol GWAS. Results Genetically predicted cortisol was associated with reduced risk of obesity class I (OR = 0.905; 95% CI, 0.865-0.946; p < 0.001). Evidence from bi-directional MR showed that obesity class II and class III were associated with lower cortisol levels ((class II-cortisol OR = 0.953; 95% CI, 0.923-0.983; p = 0.002); (class III-cortisol OR = 0.955; 95% CI, 0.942-0.967; p < 0.001)), indicating reverse causality between cortisol and obesity. Conclusions This study demonstrates that cortisol is negatively associated with obesity and vice versa. Together, these findings suggest that blunted morning plasma cortisol secretion may be responsible for severe obesity. Regulating morning plasma secretion might be a prevention measure for obese people.

scholarly journals Deciphering the Irregular Risk of Stroke Increased by Obesity Classes: A Stratified Mendelian Randomization Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuelun Zou ◽  
Leiyun Wang ◽  
Linxiao Xiao ◽  
Zihao Xu ◽  
Tianxing Yao ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Strong Association ◽  
Class Ii ◽  
The Body ◽  
Class I ◽  
Large Artery ◽  
Class Iii ◽  
Obesity Class ◽  
The Relationship

BackgroundTo investigate the relationship between different classes of obesity and stroke, we conducted a stratified Mendelian randomization (MR) study.MethodsThe body mass index (BMI) data of 263,407 Europeans with three classes of obesity (obesity class I, 30 kg/m2 ≤ BMI < 35 kg/m2; obesity class II, 35 kg/m2 ≤ BMI < 40 kg/m2; obesity class III, 40 kg/m2 ≤ BMI) were extracted from the Genetic Investigation of ANthropometric Traits (GIANT) consortium. Summary-level data of stroke and its subtypes [ischemic stroke (IS) and intracerebral hemorrhage (ICH)] were obtained from the genome-wide association study (GWAS) meta-analysis, which was performed by the MEGASTROKE consortium. MR methods were used to identify the causal relationships.ResultsThe MR analysis revealed that both obesity class I [odds ratio (OR) = 1.08, 95% CI: 1.05–1.12, p = 1.0 × 10-5] and obesity class II (OR = 1.06, 95% CI: 1.03–1.09, p = 1 × 10-4) were significantly positively related to IS, while obesity class III was not (OR = 1.01, 95% CI: 0.96–1.06, p = 0.65). In contrast to IS, there was no class of obesity associated with ICH risk. Further examination of the relationship between obesity classification and IS subtypes revealed that certain degrees of obesity were related to large artery stroke (LAS) (OR = 1.14, 95% CI: 1.04–1.24, p = 2.8 × 10-3 for class I; OR = 1.08, 95% CI: 1.01–1.16, p = 0.002 for class II) and cardioembolic stroke (CES) (OR = 1.11, 95% CI: 1.02–1.20, p = 0.02 for class I; OR = 1.08, 95% CI: 1.02–1.15, p = 0.007 for class II).ConclusionsA higher risk of IS, but not ICH, could be linked to obesity classes I and II. A strong association between LAS and CES and obesity was observed among all IS subtypes in the obese population.

scholarly journals Outcomes Amongst Obesity Class I, II, and III Patients Undergoing Minimally Invasive Aortic Valve Replacement

2021 ◽  
Author(s):  
Marlena Sabatino ◽  
NaYoung Yang ◽  
Fady Soliman ◽  
Joshua Chao ◽  
ALEXIS OKOH ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Minimally Invasive ◽  
Valve Replacement ◽  
Class Ii ◽  
Valve Surgery ◽  
Class I ◽  
Obese Patients ◽  
Class Iii ◽  
Obesity Class

Background: Minimally invasive heart valve surgery has previously been shown to be safe and feasible in obese patients. Within this population, we investigated the effect of obesity class on the patient outcomes of minimally invasive aortic valve replacement (mini-AVR). Methods: A single center retrospective cohort study of consecutive patients with obese body mass indices (BMIs) who underwent mini-AVR between 2012 and 2018. Patients were stratified into 3 groups according to Centers for Disease Control and Prevention adult obesity classifications: Class I (BMI 30.0 to < 35.0), Class II (BMI 35.0 to < 40.0), and Class III (BMI ≥ 40.0). The primary outcomes were postoperative length of stay (LOS), 30-day mortality within, and cost. Results: Amongst 182 obese patients who underwent mini-AVR, LOS (Class I 4 [3-6] vs. Class II 4 [3-6] vs. Class III 5 [4-6] days; p=0.098) and costs (Class I $24,487 [$20,199-$27.480] vs. Class II $22,921 [$20,433-$27,740] vs. Class III $23,886 [$20,063-$33,800] USD; p=0.860) did not differ between obesity class cohorts. Postoperative 30-day mortality (Class I 2.83% [n=2] vs. Class II 0% [n=0] vs. Class III 0% [n=0]; p=0.763) was limited by an insufficient sample size relative to a low event rate but did not differ between patient cohorts. Conclusions: Mini-AVR is safe and feasible to perform for obese patients regardless of their obesity class. Patients with obesity should be afforded the option of minimally invasive aortic valve surgery regardless of their obesity class.

scholarly journals The role of obesity in the development of labor and postpartum abnormalities

2018 ◽  
Vol 99 (4) ◽  
pp. 575-579
Author(s):  
R S Asakeeva ◽  
Ch K Kalkanbaeva ◽  
G K Zhalieva ◽  
F R Niyazova ◽  
N Dzh Shoonaeva
Keyword(s):  
Cesarean Section ◽  
Postpartum Period ◽  
Negative Impact ◽  
Class Ii ◽  
Class I ◽  
Control Group ◽  
Excess Body Weight ◽  
Class Iii ◽  
Obesity Class ◽  
Birth Records

Aim. Comparative assessment of the features of the course of labor and postpartum period in women with obesity of various classes. Methods. During 2014-2016, a cohort retrospective and prospective study included 318 birth records. The main group consisted of 198 case records of women with different severity of obesity (122 with obesity class I, 57 with class II and 19 with class III), and the control group included 120 case records of women without obesity. Results. In women with obesity class II and III (p=0.003 and p <0.001) had preterm birth more often than in the control group. Patients with obesity class III had the cesarean section significantly more often than in the control group (p=0.043), in the same group hypertensive disorders in labor and intrauterine hypoxia of the fetus developed more frequently (p=0.009 and p=0.039). In the postpartum period with class III obesity, postpartum haemorrhage was significantly more frequent than in the control group (p=0.045). Among complications of postpartum period in patients with obesity class II, a loychiometer (by 1.7 times), endometritis (by 1.6 times), complications after cesarean section (by 2.1 times) were registered more often than in the control group, and in obesity class III - subinvolution of the uterus (by 2.1 times), endometritis (by 2.4 times), complications after cesarean section (by 3.2 times), divergence of the seams on the perineum (by 2.4 times), but these parameters were not statistically significantly different. Conclusion. The negative impact of excess body weight on the labor course was shown, moreover, labor in obesity class I is more favorable than in class II and III.

scholarly journals The role of linoleic acid in asthma and inflammatory markers: a Mendelian randomization study

2019 ◽  
Vol 110 (3) ◽  
pp. 685-690 ◽  
Author(s):  
Jie V Zhao ◽  
C Mary Schooling
Keyword(s):  
Linoleic Acid ◽  
Blood Cell ◽  
White Blood Cell ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Uk Biobank ◽  
Reverse Causality ◽  
The Uk

ABSTRACT Background Asthma is a common respiratory disease, possibly caused by autoimmunity. Linoleic acid (LA), the main n–6 (ω-6) PUFA from widely used vegetable oils, is thought to suppress immune responses that might have benefits for asthma. However, this question has not been examined in randomized controlled trials. Objectives To obtain unconfounded estimates, we assessed how genetically predicted LA affected asthma using 2-sample Mendelian randomization. We also examined its role in white blood cell traits (eosinophil, neutrophil, and low monocyte counts) identified as potential causal factors in asthma. Methods We used 18 uncorrelated, genome-wide significant genetic variants to predict LA, which we applied to a large genetic case (n = 19,954)–control (n = 107,715) study of asthma, to the UK Biobank (408,961 people of European ancestry with 26,332 asthma cases), and for white blood cell traits to the UK Biobank. We also repeated the analysis on asthma using 29 replicated, functionally relevant genetic variants. In addition, we examined the role of asthma in LA to assess reverse causality. Results Genetically predicted LA was associated with lower risk of asthma (OR: 0.89 per SD increase in LA; 95% CI: 0.85, 0.93), with no association of asthma with LA. Genetically predicted LA was associated with lower eosinophil count (−0.03; 95% CI: −0.061, −0.004) and lower neutrophil count (−0.04; 95% CI: −0.057, −0.023). These estimates were robust to different selections of genetic variants and sensitivity analyses. Conclusions LA might protect against asthma possibly via white blood cell traits, with relevance to the identification of effective new interventions for asthma.

scholarly journals Impact of body mass index on 90-day warfarin requirements: a retrospective chart review

2021 ◽  
Vol 15 ◽  
pp. 175394472110128
Author(s):  
Bolanle M. Soyombo ◽  
Ashley Taylor ◽  
Christopher Gillard ◽  
Candice Wilson ◽  
Janel Bailey Wheeler
Keyword(s):  
Body Mass ◽  
Chart Review ◽  
Warfarin Dose ◽  
Retrospective Chart Review ◽  
Good Control ◽  
Class Ii ◽  
Class I ◽  
Secondary Outcome ◽  
Class Iii ◽  
Obesity Class

Background: Rates of obesity continue to rise worldwide as evidenced in the 2017 Centers for Disease Control and Prevention (CDC) report that indicated over 35% of United States (US) citizens are obese, with Louisiana ranked as the fifth most obese state in America. Since large clinical trials tend to exclude obese patients, health care providers are faced with concerns of under- or overdosing these patients on warfarin. Methods: This retrospective chart review evaluated patients who reported to a community anticoagulation clinic for warfarin management between 1 June 2017 and 30 September 2017. Along with baseline demographics, chronic use of drugs that have clinically significant interactions with warfarin, social activity such as tobacco use and alcohol consumption, were collected. Body mass indexes (BMI) were collected and categorized according to the World Health Organization definitions as follows: Normal (BMI 18–24.9 kg/m2), Overweight (25–29.9 kg/m2), Obesity Class I (30–34.9 kg/m2), Obesity Class II (35–39.9 kg/m2), Obesity Class III (⩾40 kg/m2). The primary outcome was the mean 90-day warfarin dose required to maintain “intermediate control” or “good control” of international normalized ratio (INR), stratified by BMI classifications. The secondary outcome was the time in therapeutic range (TTR) stratified by BMI classifications. Results: A total of 433 patient encounters were included in this study. There was a total of 43 encounters in the Normal BMI category, 111 Overweight encounters, 135 Obesity Class I encounters, 45 Obesity Class II encounters, and 99 Obesity Class III encounters. Approximately 63% of the study population were male, and over 90% the patients were African American. The Obesity Class I and Obesity Class II class required an average of 11.47 mg and 17.10 mg more warfarin, respectively, to maintain a therapeutic INR when compared with the Normal BMI category. These findings were statistically significant with p values of 0.007 and <0.001, respectively. Additionally, upon comparing the Overweight BMI category with the Obesity Class II category, there was a mean warfarin dose difference of 11.22 mg ( p = 0.010) more in Obesity Class II encounters to maintain a therapeutic INR. In the secondary analysis of TTR, Overweight category encounters had the highest TTR, whereas encounters in the Normal BMI category had the lowest TTR. Conclusion: As BMI increases, there is an increased chronic warfarin requirement to maintain “intermediate control” or “good control” of INR between 2 and 3 in an ambulatory care setting.

Caution against examining the role of reverse causality in Mendelian Randomization

2021 ◽  
Author(s):  
Sharon M. Lutz ◽  
Ann Chen Wu ◽  
John E. Hokanson ◽  
Stijn Vansteelandt ◽  
Christoph Lange
Keyword(s):  
Mendelian Randomization ◽  
Reverse Causality

scholarly journals Environmental Cadmium Exposure and Dental Indices in Orthodontic Patients

Healthcare ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 413
Author(s):  
Hui-Ling Chen ◽  
Jason Chen-Chieh Fang ◽  
Chia-Jung Chang ◽  
Ti-Feng Wu ◽  
I-Kuan Wang ◽  
...  
Keyword(s):  
Cadmium Concentration ◽  
Class Ii ◽  
Cadmium Exposure ◽  
Class I ◽  
P Value ◽  
Tooth Decay ◽  
Class Iii ◽  
Orthodontic Patients ◽  
Urine Cadmium ◽  
The Mean

Background. Previous studies have shown that environmental cadmium exposure could disrupt salivary gland function and is associated with dental caries and reduced bone density. Therefore, this cross-sectional study attempted to determine whether tooth decay with tooth loss following cadmium exposure is associated with some dental or skeletal traits such as malocclusions, sagittal skeletal pattern, and tooth decay. Methods. Between August 2019 and June 2020, 60 orthodontic patients with no history of previous orthodontics, functional appliances, or surgical treatment were examined. The patients were stratified into two groups according to their urine cadmium concentrations: high (>1.06 µg/g creatinine, n = 28) or low (<1.06 µg/g creatinine, n = 32). Results. The patients were 25.07 ± 4.33 years old, and most were female (female/male: 51/9 or 85%). The skeletal relationship was mainly Class I (48.3%), followed by Class II (35.0%) and Class III (16.7%). Class I molar relationships were found in 46.7% of these patients, Class II molar relationships were found in 15%, and Class III molar relationships were found in 38.3%. The mean decayed, missing, and filled surface (DMFS) score was 8.05 ± 5.54, including 2.03 ± 3.11 for the decayed index, 0.58 ± 1.17 for the missing index, and 5.52 ± 3.92 for the filled index. The mean index of complexity outcome and need (ICON) score was 53.35 ± 9.01. The facial patterns of these patients were within the average low margin (26.65 ± 5.53 for Frankfort–mandibular plane angle (FMA)). There were no significant differences in the above-mentioned dental indices between patients with high urine cadmium concentrations and those with low urine cadmium concentrations. Patients were further stratified into low (<27, n = 34), average (27–34, n = 23), and high (>34, n = 3) FMA groups. There were no statistically significant differences in the urine cadmium concentration among the three groups. Nevertheless, a marginally significant p-value of 0.05 for urine cadmium concentration was noted between patients with low FMA and patients with high FMA. Conclusion. This analysis found no association between environmental cadmium exposure and dental indices in our orthodontic patients.

scholarly journals A convenient method of preparation of high-activity urease from Canavalia ensiformis by covalent chromatography and an investigation of its thiol groups with 2,2'-dipyridyl disulphide as a thiol titrant and reactivity probe

1976 ◽  
Vol 159 (2) ◽  
pp. 245-257 ◽  
Author(s):  
R Norris ◽  
K Brocklehurst
Keyword(s):  
Convenient Method ◽  
Specific Activity ◽  
Class Ii ◽  
High Reactivity ◽  
Class I ◽  
Thiol Groups ◽  
Class Iii ◽  
Active Centre ◽  
Class Ib ◽  
Covalent Chromatography

1. A convenient method of preparation of jack-bean urease (EC3.5.1.5) involving covalent chromatography by thiol-disulphide interchange is described. 2. Urease thus prepared has specific activity comparable with the highest value yet reported (44.5 ± 1.47 kat/kg, Km = 3.32 ± 0.05 mM; kcat. = 2.15 × 104 ± 0.05 × 104s-1 at pH7.0 and 38°C). 3. Titration of the urease thiol groups with 2,2'-dipyridyl disulphide (2-Py-S-S-2-Py) and application of the method of Tsou Chen-Lu [(1962) Sci. Sin.11, 1535-1558] suggests that the urease molecule (assumed to have mol.wt. 483000 and ε280 = 2.84 × 105 litre·mol-1-cm-1) contains 24 inessential thiol groups of relatively high reactivity (class-I), six ‘essential’ thiol groups of low reactivity (class-II) and 54 buried thiol groups (class-III) which are exposed in 6M-guanidinium chloride. 4. The reaction of the class-I thiol groups with 2-Py-S-S-2-Py was studied in the pH range 6-11 at 25°C(I = 0.1 mol/l) by stopped-flow spectrophotometry, and the analogous reaction of the class-II thiol groups by conventional spectrophotometry. 5. The class-I thiol groups consist of at least two sub-classes whose reactions with 2-Py-S-S-2-Py are characterized by (a) pKa = 9.1, k = 1.56 × 104M-1·s-1 and (b) pKa = 8.1, k = 8.05 × 102M-1·s-1 respectively. The reaction of the class-II thiol groups is characterized by pKa = 9.15 and k = 1.60 × 102M-1·s-1. 6. At pH values 7-8 the class-I thiol groups consist of approx. 50% class-Ia groups and 50% class-Ib groups. The ratio class Ia/class Ib decreases as the pH is raised according to a pKa value ≥ approx. 9.5, and at high pH the class-I thiol groups consist of at most 25% class-Ia groups and at least 75% class-Ib groups. 7. The reactivity of the class-II thiol groups towards 2-Py-S-S-2-Py is insensitive to the nature of the group used to block the class-I thiols. 8. All the ‘essential’ thiol groups in urease appear to be eeactive only as uncomplicated thiolate ions. The implications of this for the active-centre chemistry of urease relative to that of the thiol proteinases are discussed.

Regulation of mouse CYP1A1 gene expression by dioxin: requirement of two cis-acting elements during induction

1989 ◽  
Vol 9 (6) ◽  
pp. 2378-2386
Author(s):  
L A Neuhold ◽  
Y Shirayoshi ◽  
K Ozato ◽  
J E Jones ◽  
D W Nebert
Keyword(s):  
Gene Expression ◽  
Simian Virus 40 ◽  
Class Ii ◽  
Simian Virus ◽  
Class I ◽  
Ah Receptor ◽  
Class Iii ◽  
Cis Acting ◽  
Cyp1a1 Gene ◽  
Sv40 Dna

The mouse cytochrome P1450 (CYP1A1) gene is responsible for the metabolism of numerous carcinogens and toxic chemicals. Induction by the environmental contaminant tetrachlorodibenzo-p-dioxin (TCDD) requires a functional aromatic hydrocarbon (Ah) receptor. We examined the 5'-flanking region of the CYP1A1 gene in mouse hepatoma Hepa-1 wild-type cells and a mutant line having a defect in chromatin binding of the TCDD-receptor complex. We identified two cis-acting elements (distal, -1071 to -901 region; proximal, -245 to -50 region) required for constitutive and TCDD-inducible CYP1A1 gene expression. Three classes of DNA-protein complexes binding to the distal element were identified: class I, found only in the presence of TCDD and a functional Ah receptor, that was heat labile and not competed against by simian virus 40 (SV40) early promoter DNA; class II, consisting of at least three constitutive complexes that were heat stable and bound to SV40 DNA; and class III, composed of at least three constitutive complexes that were thermolabile and were not competed against by SV40 DNA. Essential contacts for these proteins were centered at -993 to -990 for the class I complex, -987, -986, or both for the class II complexes, and -938 to -927 for the class III complexes. The proximal element was absolutely essential for both constitutive and TCDD-inducible CYP1A1 gene expression, and at least two constitutive complexes bound to this region. These data are consistent with the proximal element that binds proteins being necessary but not sufficient for inducible gene expression; interaction of these proteins with those at the distal element was found to be required for full CYP1A1 induction by TCDD.

Prevalence of Malocclusions in Autistic Patients in Isfahan

2021 ◽  
Author(s):  
Zahra Ali Mehtari ◽  
Mehdi Rafiei ◽  
Saeed Azarbayjani ◽  
Neda Ahmadi Rouzbehani ◽  
Amir Hossain Moeini
Keyword(s):  
Class Ii ◽  
Autism Spectrum ◽  
Open Bite ◽  
Class I ◽  
Dental Student ◽  
Class Iii ◽  
Cross Sectional ◽  
Deep Bite ◽  
Normal Occlusion ◽  
Age Range

Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders diagnosed by impairments in social interaction and communication with repetitive and restrictive stereotyped behavioral patterns. The Prevalence of autism has been reported to be increased in recent years. This study aimed to assess the prevalence of different types of malocclusion among ASD patients in Isfahan in 2018. Materials & Methods: In a descriptive and cross-sectional trial, 92 ASD patients were studied in the age range of 7-18 years at the center for autism patients in Isfahan. Clinical oral examinations of patients are taken to assess the involved malocclusions (Cl I, Cl II and Cl III malocclusions) and malocclusion traits (deep bite, open bite and cross bite) by an educated dental student under the supervision of an orthodontist under natural light. The data are reported using frequency and percentage indices. Results: Class I malocclusion had the highest prevalence 54.3% (50) among ASD patients and the prevalence of class II and class III were found to be 19.6% (18) and 7.6% (7) respectively. The frequency of malocclusions traits of deep bite, cross bite and the open bite were 27.2% (25), 18.5% (17) and 7.6% (7) respectively. Among of the total patients, 65.2% (60) showed normal bite and 18/5% (17) showed Normal occlusion. Conclusion: ASD patients showed class I, class II and class III malocclusions from the most to least frequency and the most frequent malocclusion traits were also deep bite, cross bite and open bite respectively.

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