Endocrine and Metabolic Science最新文献

Background

Weight loss is important to reduce the risk of metabolic complications in obese individuals, in whom dysregulated adipokines play a central role. This study aims to investigate whether dysregulated adipokines and postprandial triglycerides (TG) improve with a modest weight loss.

Methods

Individuals with obesity (BMI ≥ 30 kg/m²) were recruited among patients at the University Hospital of North Norway and the Stamina Health weight loss rehabilitation program. We measured resting energy expenditure (REE), and calculated the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), leptin to adiponectin (L:A) ratio, indirect leptin sensitivity (REE:leptin ratio), postprandial TG clearance at 6 h, and TG response before and after weight loss. The goal of the weight loss intervention was a loss of ≥5 % of initial total body weight.

Results

28 participants completed the study, of which 13 lost ≥ 5 % body weight and 18 lost <5 % body weight. HOMA-IR (−23.1 %), REE:leptin ratio (+80.1 %) and L:A ratio (−45.7 %) significantly improved with weight loss, whereas there was no improvement of postprandial TG response or clearance. No significant changes were observed in the non-weight loss group.

Conclusion

The data are consistent with the general concept that modest weight loss in obese patients may restore metabolic regulation by improving L:A ratio and insulin and leptin sensitivity.

Thyroid Hormone Receptor (THR) is a member of the nuclear receptor (NR) superfamily, best defined as intracellular ligand-modulated transcription factors. Thyroid hormone (TH), by binding to THR, regulates several physiological and metabolic processes, e.g., development, metabolism, homeostasis, reproduction, etc. THR primarily heterodimerizes with RXR and binds to its response element to modulate the expression of the target genes. THR has two different isoforms differentially expressed throughout the body, i.e., THRα and THRβ, encoded by two distinct genes, THRA and THRB, respectively. The indispensable roles of THRβ in the regulation of the hypothalamus-pituitary-thyroid in addition to biochemical processes, including metabolism, hepatic and kidney-related functions, etc., illustrate that receptor dysregulations are the underlying cause of the onset of several diseases, including diabetes, cardiac ailments, metabolic-related disorders, endocrine-related cancers, reproductive issues, etc. This also makes it a potential target for pharmacological interventions. In this context, the present review focuses mainly on the intrinsic mechanism of THRβ functioning and its contribution to disease progression. In addition, several genetic/polymorphic variations in the THRB gene that are primary driving factors in eliciting rare genetic disorder, i.e., resistance to thyroid hormone (RTH), have also been addressed in detail. We have also highlighted the implications of THR targetability by addressing the impact of TH analogs/modulators and thyroid hormone-disrupting chemicals in disease occurrence and its management.

The Wilms tumor suppressor gene (WT1) is a transcription factor with a wide array of functions, that affects the differentiation and survival of several cell types in different organs. It plays a special role in renal and gonadal development, organs in which WT1 deleterious variants determine well-established conditions, such as Wilms tumor, corticosteroid-resistant nephropathy with progression to loss of renal function, and a spectrum of gonadal development abnormalities (XX and XY gonadal dysgenesis, XX testicular and XX ovotesticular) and testicular tumors. Moreover, WT1 variants are also associated with urinary tract malformations, heart and nervous system diseases, diaphragmatic hernias, leukemia, and tumorigenesis. Consequently, an increasingly broad phenotypic spectrum has been associated with WT1 deleterious variants in 46,XX, and 46,XY individuals. The genotype-phenotype causal relationship involving WT1 pathogenic variants and their heterogeneous clinical manifestations is also discussed.

This review summarizes current knowledge regarding the clinical implications of WT1 disorders and highlights the importance of diagnosing deleterious variants of WT1 for the early identification of individuals at high risk of developing severe phenotypes, for the adequate planning of the therapeutic approach, and for familiar genetic counseling.

Introduction

It seems that the risk of developing diabetes cannot be predicted solely based on weight or BMI. Metabolic phenotypes might offer a more precise tool for identifying patients at higher risk of diabetes, thus enabling more effective and targeted preventive interventions.

Objective

To determine the association between these metabolic phenotypes and the risk of diabetes.

Materials

Systematic Review (SR) with a meta-analysis of cohort studies. The search was carried out in four databases: Pubmed/Medline, SCOPUS, Web of Science, and EMBASE. Metabolic states were classified into six groups: Metabolically Healthy Normal Weight (MHNW), Metabolically Unhealthy Normal Weight (MUNW), Metabolically Healthy Overweight (MHOW), Metabolically Unhealthy Overweight (MUOW), Metabolically Healthy Obesity (MHO), and Metabolically Unhealthy Obesity (MUO). Association measures were presented as odds ratios (OR) and hazard ratios (HR) along with their 95 % confidence intervals (CI95%).

Results

A total of six studies were evaluated. For the meta-analysis, only studies using OR as the measure of association were included. Compared with individuals with MHNW, a statistically significant association was found for MUNW (OR: 1.82; CI95% 1.62, 2.04), MHOW (OR: 1.19; CI95% 1.07, 1.32), MUOW (OR: 2.44; CI95% 2.19, 2.72), MHO (OR: 2.14; CI95% 1.52, 3.01), and MUO (OR: 3.94; CI95% 3.28, 4.74).

Conclusions

Metabolic phenotypes are significantly associated with the risk of diabetes, regardless of BMI. Further research in this field is required, and should be conducted in other regions of the world where obesity and diabetes rates are rapidly increasing.

Introduction

Although body mass index (BMI) and waist circumference (WC) are the most commonly used obesity markers in clinical practice regarding depression, some studies suggest that other obesity markers such as waist-to-height ratio (WHtR), a body shape index (ABSI), body roundness index (BRI), and conicity index (CI) may be more accurate in identifying patients with depression.

Objective

To determine the relationship between different markers of obesity and the presence of symptoms of depression.

Methods

Analytical cross-sectional study. A secondary analysis was conducted on the Demographic and Family Health Survey (ENDES) from 2018 to 2021. The main variable of the present study was the depression score. Numerical variables were presented as mean and confidence interval at 95 % (CI 95 %). A generalized linear model of the Gaussian family and Identity link function was performed to evaluate the strength of association between the variables of interest.

Results

The average depression score in the study population was 2.61 (95 % CI 2.56–2.65). In the multivariable analysis, the depression score increased for each unit that increased the BMI by 0.011 points (β = 0.011; 95 % CI 0.002–0.020), the WHtR by 0.207 points (β = 0.207; 95 % CI 0.145–0.267), the ABSI by 0.158 points (β = 0.158; IC95% 0.047–0.269), the BRI by 0.096 points (β = 0.096; IC95% 0.069–0.122), and the CI by 0.010 points (β = 0.010; IC95% 0.004–0.016). There was no statistically significant association for WC.

Conclusions

The WHtR may be a better marker of obesity for identifying patients with depressive symptoms compared to other markers.

Low neighborhood social cohesion (nSC) has been associated with obesity. Still, few studies have assessed the nSC-obesity relationship among a large, nationally representative, and racially/ethnically diverse sample of the United States population. To address this literature gap, we examined cross-sectional associations among 154,480 adult participants of the National Health Interview Survey (NHIS) from 2013 to 2018. We also determined if associations varied by race/ethnicity, sex/gender, age, annual household income, and food security status. Based on a 4-item scale from the Project on Human Development in Chicago Neighborhoods Community Survey, we categorized nSC as low, medium, and high. Based on body mass index (BMI) recommendations, we categorized obesity as ≥30 kg/m². We used Poisson regression with robust variance to directly estimate prevalence ratios (PRs) and 95 % confidence intervals (CIs) while adjusting for sociodemographic characteristics, such as annual household income, educational attainment, and marital status, along with other confounders. Study participants' mean age ± standard error was 47.1 ± 0.1 years; most (69.2 %) self-identified as Non-Hispanic (NH)-White; and 51.0 % were women. NH-Black and Hispanic/Latinx adults comprised more of the population in neighborhoods with low nSC (14.0 % NH-Black, 19.1 % Hispanic/Latinx, and 61.8 % NH-White) versus high nSC (7.7 % NH-Black, 10.4 % Hispanic/Latinx and 77.0 % NH-White). Low vs. high nSC was associated with a 15 % higher prevalence of obesity (PR = 1.15 [95 % CI: 1.12–1.18]), and the magnitude of the association was more substantial among NH-White adults (PR = 1.21 [95 % CI: 1.17–1.25]) compared to associations among Hispanic/Latinx (PR = 1.04 [95 % CI: 0.97–1.11]) and NH-Black (PR = 1.01 [95 % CI: 0.95–1.07]) adults. Low vs. high nSC was associated with a 20 % higher prevalence of obesity in women (PR = 1.20 [95 % CI: 1.16–1.24]) compared to a 10 % higher prevalence in men (PR = 1.10 [95 % CI: 1.06–1.14]). Low vs. high nSC was associated with a 19 % higher prevalence of obesity among adults ≥50 years old (PR = 1.19 [95 % CI: 1.15–1.23]) compared to a 7 % higher prevalence of obesity among adults <50 years old (PR = 1.07 [95 % CI: 1.03–1.11]). Efforts to address nSC may improve health and address health disparities.

The application of artificial fruit ripeners has become a great burden to the public health clinicians. This study assessed the toxicity effect of ethylene glycol (EOGH) and plantain peel fraction ripened with calcium carbide (CaC₂) on male reproductive functions. Forty male rats were divided into five groups (n = 8). Group 1 received distilled water only; group 2 received 200 mg/m³ ethylene glycol; group 3 received 1000 mg/kg of CaC₂; group 4 received 200 mg/kg plantain peel extract (PPE) and group 5 received 200 mg/kg plantain-peel extract ripened with CaC₂ (PPECC). The exposure via oral route lasted for 14 days. Sub-acute exposure of male rats to ethylene glycol, CaC₂ and PPECC elicited spermatogenic lesions through significant (p < 0.05) depletion of testosterone level, daily sperm production, sperm motility, live sperm and sperm count with elevated sperm deformity and testicular 5¹-nucleotidase activity upon exposure to ethylene-glycol, CaC₂ and PPECC in relation to PPE. Also, exposure to ethylene glycol, CaC₂ and PPECC remarkably increased testicular MDA content and serum AST, ALT and ALP activities which predisposes to spermatogenic abnormalities. Altogether, application of PPECC is suggested as one of the risk factors of liver failure associated with reproductive disruption in rat model.

Introduction

African Americans (AAs) have the highest prevalence of hypertension among United States racial/ethnic groups. Regulators of blood pressure, such as aldosterone and endothelin-1, impact glucose regulation. The relationship between these factors and incident diabetes is not well elucidated among AAs.

Methods

Among 3914 AA participants without prevalent diabetes in the Jackson Heart Study, linear regression models were used to examine cross-sectional associations of exposures (aldosterone, endothelin-1, and a combined aldosterone-endothelin-1 score [2–8]) with glycemic measures (fasting plasma glucose [FPG], HbA1c, homeostatic model assessments of beta cell function [HOMA-β] and insulin resistance [HOMA-IR]). Longitudinal associations of exposures with incident diabetes were examined using Cox proportional hazard models. Models were adjusted for age, sex, education, occupation, systolic blood pressure, smoking, physical activity, dietary intake, alcohol use and adiponectin.

Results

Aldosterone and the combined aldosterone-endothelin score were positively associated with FPG, HOMA-IR, and HOMA-β (all p < 0.05). Endothelin-1 was negatively associated with FPG but positively associated with HOMA-β (both p < 0.05). Only the aldosterone-endothelin score was positively associated with HbA1c (p < 0.01). A 1-SD higher serum aldosterone and endothelin-1 was associated with a 22 % and 14 % higher risk of incident diabetes, respectively, while a 1-point higher aldosterone-endothelin score was associated with a 13 % higher risk of incident diabetes after adjustment for diabetes risk factors (all p < 0.01).

Conclusions

Aldosterone and endothelin-1, factors integral in blood pressure regulation, may play a significant role in the development of diabetes among AAs.