Hormones-International Journal of Endocrinology and Metabolism最新文献

Objective: Our study aims to examine the associations of thyroid function parameters with phenotypic age acceleration (PhenoAgeAccel) in different age groups.

Method: The analysis included 7,564 participants from the NHANES 1999-2018. PhenoAgeAccel was defined as calculated phenotypic age (PhenoAge) exceeding chronological age. Weighted multivariable logistic regression models were used to analyze the relationship between free triiodothyronine (FT3) and PhenoAgeAccel. The restricted cubic spline method was used to assess nonlinear associations of FT3 level with PhenoAgeAccel. Nomogram and the receiver operating characteristic (ROC) curve were constructed to evaluate the diagnostic performance of the predictive model.

Results: Higher FT3 levels were associated with increased risk of PhenoAgeAccel in participants under 60 years old (OR: 1.316, 95% CI: (1.010, 1.715), p = 0.042). For those aged 60 years and above, higher FT3 levels were linked with decreased risk of PhenoAgeAccel (OR: 0.485, 95% CI: (0.309, 0.761), p = 0.002). These associations were more pronounced in males than in females. Restricted cubic spline curves showed similar trends between FT3 levels and PhenoAgeAccel in both age subgroups. The ROC curves including FT3 indicated that both models had fair prediction performance (age >  = 60 years, AUC = 0.722 (0.700-0.743); age < 60 years, AUC = 0.765 (0.751- 0.780)).

Conclusion: This study revealed a novel age-dependent association between FT3 levels and biological aging acceleration, with lower FT3 potentially serving as a biomarker for accelerated aging in elderly individuals, while an inverse relationship was observed in younger adults. The study provides novel insights into the intricate relationship between thyroid function and systemic health across the lifespan.

Introduction: Acromegaly is a chronic disease characterized by excessive growth hormone (GH) secretion leading to high insulin-like growth factor 1 (IGF- 1) levels. It results in systemic complications, including vertebral fractures (VFs), which impair quality of life. Bone mineral density (BMD) may not fully capture fracture risk, warranting further research into alternative predictors and mitigation strategies.

Objectives: This study aimed to assess the prevalence of VFs in patients with acromegaly and identify associated risk factors.

Methods: A multicenter, cross-sectional study was conducted at three centers in Saudi Arabia and one in the United Arab Emirates (UAE). Data for patients with acromegaly evaluated between 2010 and 2024 were reviewed.

Results: The cohort consisted of 101 patients (63% male) with a median age of 45 years and an median disease duration of 7 years. VFs were present in 10 patients, predominantly affecting the lumbar spine and were generally mild. Although not statistically significant, patients with VFs had longer disease durations. BMD measurements did not significantly differ between those with and without VFs; however, patients with VFs showed a trend toward lower trabecular bone score (TBS), suggesting compromised bone microarchitecture.

Conclusion: This study underscores the importance of comprehensive bone health assessment in patients with acromegaly incorporating BMD, TBS, and hormonal evaluations. Continuous long-term monitoring of bone health parameters is necessary in this population. Future research is needed to delineate risk factors associated with VFs.

Ischemia-reperfusion (I/R) injury is a significant cause of testicular damage, leading to infertility and other reproductive dysfunctions. Antioxidant therapies have emerged as a potential intervention to mitigate oxidative stress and cellular damage. This study investigates the effects of somatostatin (SST) and N-acetylcysteine (NAC) on testicular damage induced by I/R, focusing on their antioxidant and cellular protective effects. Twenty-four male rats were divided into four groups, as follows: sham operated, I/R injury, I/R + somatostatin treatment, and I/R + NAC treatment. A testicular I/R injury was induced surgically, followed by either SST or NAC administration. Testicular tissues were assessed histopathologically using hematoxylin and eosin staining and employing Johnson's biopsy scoring. Immunohistochemical analyses were performed for caspase- 3, 8-hydroxy- 2'-deoxyguanosine (8-OHdG), testis-specific histone 2B, and testosterone to evaluate apoptosis, oxidative DNA damage, cellular proliferation, and steroidogenesis, respectively. Serum levels of testosterone and follicle-stimulating hormone (FSH) were measured by biochemical analysis. The results showed that both SST and NAC treatments significantly ameliorated histopathological damage and reduced the levels of caspase- 3 and 8-OHdG, indicating reduced apoptosis and oxidative DNA damage. Furthermore, increased testis-specific histone 2B positivity suggested enhanced cellular proliferation. Notably, administration of SST decreased testosterone positivity in the testis, whereas NAC treatment increased it. However, no significant differences in serum testosterone levels were observed between the NAC and SST groups. In addition, serum FSH levels of the I/R + SST group were found to be significantly higher than those of the control group. SST and NAC exhibit protective effects against testicular damage induced by I/R, as evidenced by their antioxidant and anti-apoptotic properties. The differential impact on testosterone positivity in the testis tissue highlights distinct underlying mechanisms, warranting further investigation. Despite these promising findings, the lack of significant changes in serum hormone levels calls for additional studies to fully elucidate the therapeutic potential and mechanistic pathways of SST and NAC in the context of testicular I/R injury.

When it comes to nutritional status and physical performance, body composition is significant. Previous research has shown the correlation between body composition and the mismatch between nutrient intake and requirements. However, this paper aims to evaluate the crucial role of lifestyle factors, such as eating behavior and meal timing, in influencing body composition. Lifestyle variables are important because they affect hormone and growth factor imbalances, which can cause changes in protein synthesis or breakdown, insulin resistance, and overeating. These factors collectively affect muscle mass and fat mass, their influence being consistent across juvenile and adult groups, between men and women. Regarding food preferences, sexual dimorphism of adiposity between men and women seems to be a critical determinant. Additionally, chronic stress leads to emotional eating, while enough sleep plays a big role in affecting growth factors and hormone balances, although the research on this subject is as yet scant. Therefore, understanding and modifying lifestyle habits are essential for the improvement of body composition, irrespective of an individual's gender or age.

Background: Urinary iodine concentration (UIC) is related to prediabetes and diabetes; nevertheless, there is still a dearth of data about the association of UIC with all-cause mortality in diabetics.

Objective: To investigate the connection between UIC and all-cause mortality in diabetics.

Methods: Data from NHANES, collected on adult Americans between 2005 and 2018, were used in this investigation. The associations between ln-transformed creatinine-adjusted UIC (urinary iodine/creatinine, UI/Cr) and all-cause mortality in diabetics, as well as in older diabetics with a history of thyroid disease, were analyzed using Cox proportional hazards models and survival curve analysis. Subgroup analyses and interaction tests were conducted to examine variables affecting the association between ln(UI/Cr) and all-cause mortality in people with diabetes. Lastly, the effect of smoking on this association was tested by using restricted cubic spline (RCS).

Results: A total of 2,141 participants were included in this study. ln(UI/Cr) was significantly associated with a higher risk of all-cause mortality in diabetics in the unadjusted model (HR= 1.38, 95% CI: 1.20 - 1.58, P<0.001), but this association lost significance when confounding variables were considered (P> 0.05). Subgroup analysis revealed that Mexican-Americans and females had a stronger positive connection (P<0.05) between ln(UI/Cr) and the risk of all-cause mortality among diabetics. There was a significant correlation between ln(UI/Cr) and mortality in female smokers with diabetes (95% CI: 1.16 - 2.18, P=0.004). The RCS analysis demonstrated a significant non-linear relationship (P-non-linear= 0.0131). ln(UI/Cr) was significantly and positively associated with all-cause mortality in elderly diabetic individuals with a history of thyroid disease (HR= 1.38, 95% CI: 1.01 - 1.87, P=0.042).

Conclusion: In American individuals with diabetes, our research validates the association between UI/Cr and all-cause mortality. This correlation might offer additional dietary suggestions for the management of individuals with diabetes.

Background: Obesity is often associated with elevated leptin levels and leptin resistance, which can lead to impaired reproductive function. While exogenous leptin is known to enhance reproductive capacity in leptin-deficient male mice, its effects on reproductive function in obese male mice and the underlying mechanisms remain unclear. This study aims to elucidate the effects of leptin on testicular tissue, semen, and associated signaling pathways in both normal and obese male mice.

Methods: A high-fat diet-induced obesity model was established in male C57BL/6 J mice, followed by the administration of exogenous leptin. Histological changes in testicular tissue were observed using HE staining, while RT-PCR was employed to investigate mRNA expression levels of leptin and its receptor. The expression of proteins involved in leptin-related signaling pathways was analyzed by Western blotting.

Results: Both high-fat diet-induced obesity and exogenous leptin administration led to significant alterations in testicular histomorphology, semen parameters, and reproductive hormones, ultimately impairing fertility. Leptin intervention significantly decreased FSH and LH levels, along with a reduction in serum leptin levels and the expression of leptin and its receptor mRNA. Moreover, exogenous leptin promoted the phosphorylation of STAT3, ERK, and AMPK, suggesting activation of these signaling pathways.

Conclusions: Normal mice exhibited negligible responses to exogenous leptin, whereas obese mice showed significant leptin resistance, likely due to the opposing signaling pathways that modulate leptin's effects. This study highlights the differential impact of leptin on reproductive function between normal and obese mice, with leptin resistance in obese mice potentially serving as a protective mechanism against reproductive damage.

Objective: This randomized controlled trial aimed to compare the effects of dulaglutide alone versus dulaglutide combined with probiotics on cardiovascular risk factors, pancreatic beta-cell function, and gut microbiota in patients with type 2 diabetes mellitus (T2DM).

Methods: Sixty overweight/obese adults with T2DM (HbA1c 6.5-11%, BMI ≥ 24 kg/m²) were randomized to a control group (dulaglutide 1.5 mg/week + placebo) or an intervention group (dulaglutide 1.5 mg/week + probiotics containing Bifidobacterium longum, 2 × 10⁹ CFU/dose) for 12 weeks. Outcomes included glycemic control (HbA1c, fasting plasma glucose [FPG], 2-hour postprandial glucose [2hPG]), inflammatory markers (TNF-α, CRP), cardiovascular risk factors (blood pressure, lipids), gut microbiota, and safety.

Results: The intervention group showed greater reductions in HbA1c (- 1.06% vs. -0.35%, P = 0.028), FPG (- 4.16 vs. -3.92 mmol/L, P = 0.010), and inflammatory markers (TNF-α: -43.6% vs. -33.3%, P < 0.001). Pancreatic beta-cell function improved significantly (HOMA-β: +34.7% vs. +23.1%, P = 0.034), with increased beneficial gut microbiota (Lactobacillus: +2.1 × 10⁶ vs. +1.3 × 10⁶ CFU/g, P < 0.001). Hypertension incidence (0% vs. 13.3%, P = 0.038) and dyslipidemia (0% vs. 16.7%, P = 0.020) were lower in the intervention group. Both regimens were well-tolerated, with no severe hypoglycemia or renal/hepatic toxicity.

Conclusion: Combining dulaglutide with probiotics enhances glycemic control, reduces inflammation, and improves cardiovascular risk factors in T2DM more effectively than dulaglutide alone, likely through gut microbiota modulation. This dual approach offers a promising strategy for T2DM management, though larger long-term trials are needed to confirm cardiovascular benefits.

Background and objective: As the global population ages, the incidence of sarcopenia increases, resulting in increasing numbers of patients with impairments in physical function. Thyroid function disorders may contribute to the pathogenesis of sarcopenia. This study aimed to establish a causal relationship between thyroid hormones (TH) and sarcopenia using a two-sample Mendelian randomization (MR) analysis method.

Study design: A two-sample MR study was conducted using summary-level data from genome-wide association studies (GWAS) which included publicly available pooled statistics for thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and the FT3 to FT4 ratio from the Thyroidomics Consortium, as well as summary statistics for sarcopenia-related traits, such as appendicular lean mass (ALM), whole-body lean mass (WBLM), grip strength (left and right), and walking pace from the UK Biobank. The MR analysis used genetic exposure tools for assessment of thyroid function (TSH, FT4, FT3, and the FT3 to FT4 ratio) and outcome measures for sarcopenia (ALM, WBLM, grip strength, and walking pace). The inverse variance weighted method was employed to estimate the genetic predictions of the causal effect of thyroid function on sarcopenia risk. Sensitivity analyses were also conducted to validate the reliability of the MR results.

Results: Correlations were observed between ALM and several indicators, as follows: TSH (OR: 1.03; 95% CI: 1.01-1.04), FT4 (OR: 0.95; 95% CI: 0.93-0.98), FT3 (OR: 1.09; 95% CI: 1.03-1.15), and the FT3 to FT4 ratio (OR: 1.25; 95% CI: 1.11-1.42). Furthermore, causal relationships were identified between WBLM and TSH (OR: 1.02; 95% CI: 1.01-1.03), as well as low TSH (OR: 0.99; 95% CI: 0.99-1.00) and high TSH (OR: 0.97; 95% CI: 0.96-1.00). Walking pace was associated with low TSH (OR: 0.99; 95% CI: 0.99-1.00), whereas grip strength was related to TSH (OR: 1.01; 95% CI: 1.00-1.02) and low TSH (OR: 0.99; 95% CI: 0.99-1.00). High TSH (OR: 1.04; 95% CI: 1.01-1.08) and FT3 (OR: 0.96; 95% CI: 0.92-1.00) levels were associated with right grip strength.

Conclusion: These results indicate a causal relationship between thyroid function and sarcopenia, highlighting FT3 and the FT3 to FT4 ratio as key indicators. However, total triiodothyronine (TT3) emerges as a potential indicator that requires further investigation in future studies.

Purpose: Studies exploring the relationship between male-specific factors and risks of cardiovascular disease (CVD) are limited and inconsistent. We aimed to examine the association of male hormone levels and sexual factors (e.g., onset of puberty and baldness pattern) with CVD events.

Methods: This study included 154,970 men from the UK Biobank for prospective analyses. Cox proportional hazards regression was performed, with outcomes of CVD, coronary heart disease (CHD), stroke, and heart failure (HF), and adjusted for sociodemographics, lifestyle, and medical factors. Restricted cubic spline models assessed nonlinear associations between sex hormone levels and CVD risks.

Results: Over a median follow-up of 13.0 years, 20,216 men (13.0%) experienced a CVD event. Men in the highest quintile of total testosterone had increased stroke risk (HR 1.13, 95% CI: 1.04-1.23). A J-shaped relationship was found between sex hormone-binding globulin (SHBG) levels and CVD risk, with the highest risk in Q5 (1.08, 1.03-1.13). A U-shaped association was noted for free testosterone (FT), where Q3 had lower CVD risk (0.94, 0.90-0.98). Earlier onset of facial hair or voice breaking (< 13 years) correlated with higher CVD risks (HR 1.10, 95% CI: 1.04-1.16 and HR 1.14, 95% CI: 1.06-1.22, respectively). Vertex baldness was linked to increased CVD risk (1.05, 1.01-1.09) and CHD risk (1.06, 1.02-1.11).

Conclusions: Elevated SHBG levels, earlier puberty onset, and vertex baldness were associated with increased CVD risks in men, highlighting the need for targeted prevention strategies.

Background and aims: Chronic kidney disease (CKD) is creating an ever heavier global health burden with population ageing. This study aimed to examine the longitudinal associations of remnant cholesterol (RC) with CKD morbidity in a large high-risk population (type 2 diabetes and hypertension).

Methods: A total of 11,881 participants who participated in annual health examinations from 2021 to 2023 were included in our analysis. The Cox proportional hazards model was performed to analyze the associations of baseline RC, cumulative RC, and variability of RC with CKD morbidity. The cross-lagged panel analysis was used to examine the temporal relationship between RC and renal function.

Results: The results of the multivariable-adjusted models showed that higher baseline, cumulative RC, and variability of RC were related to higher risks of developing CKD, the adjusted HR (95% CI) comparing tertile 3 with tertile 1 were 1.26 (95% CI 1.10-1.45), 1.33 (95% CI 1.16-1.52), 1.36 (95% CI 1.20-1.55), respectively. Stratified analysis found that gender did not change these associations. Compared with individuals in the low cumulative and variability RC group, those in the high cumulative and variability RC group had a 1.62 times higher risk of CKD (95% CI: 1.34-1.96). The cross-lagged panel analysis showed that the increase in RC levels may precede the decrease in eGFR.

Conclusions: High baseline level, cumulative exposure to RC, and variability of RC are associated with increased CKD risk. Therefore, monitoring RC-related parameters is crucial to delay the occurrence and development of CKD in high-risk populations.