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Open access

SHBG levels in primary infertile men: a critical interpretation in clinical practice

Luca Boeri, Paolo Capogrosso, Walter Cazzaniga, Edoardo Pozzi, Luigi Candela, Federico Belladelli, Davide Oreggia, Eugenio Ventimiglia, Nicolò Schifano, Giuseppe Fallara, Marina Pontillo, Costantino Abbate, Emanuele Montanari, Francesco Montorsi, and Andrea Salonia

Objective:

We aimed to test the association between age, BMI and sex-hormone–binding globulin (SHBG) in a homogenous cohort of white-European men presenting for primary couple’s infertility.

Design:

Retrospective study.

Methods:

Data from 1547 infertile men were analysed. Health-significant comorbidities were scored with the Charlson comorbidity index (CCI). Fasting serum hormones were measured in every patient. Age was considered according to quartile groups (<33, 33-41, >41 years) and BMI as normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obesity (>30 kg/m2). Descriptive statistics and linear regression analysis tested the associations between age, BMI and SHBG.

Results:

Median SHBG levels increased across quartiles of age and decreased along with BMI increases (all P < 0.001). For each year increase in age, SHBG increased 0.32 nmol/L; conversely, for each unit increase in BMI, SHBG decreased by 1.1 nmol/L (all P < 0.001). SHBG levels decline with increasing BMI was greater than SHBG progressive increase with age. Overall, BMI explained 3.0 times more of the variability in SHBG than did ageing. At multivariate linear model, age and BMI were the most significant factors influencing SHBG concentration (all P < 0.001), after accounting for CCI, albumin levels and smoking status.

Conclusions:

We found a wide distribution of SHBG concentrations across age and BMI values in primary infertile men. The association between BMI and lowered SHBG levels seems to be greater than the association of ageing with increased SHBG.

DOI:
https://doi.org/10.1530/EC-20-0183
Volume 9: Issue 7,
Pages:
658–666 (9 total)
Open access

1α,25-dihydroxyvitamin D3 promotes osseointegration of titanium implant via downregulating AGEs/RAGE pathway in T2DM

Tingting Jia, Ya-nan Wang, Dongjiao Zhang, and Xin Xu

Diabetes-induced advanced glycation end products (AGEs) overproduction would result in compromised osseointegration of titanium implant and high rate of implantation failure. 1α,25-dihydroxyvitamin D3 (1,25VD3) plays a vital role in osteogenesis, whereas its effects on the osseointegration and the underlying mechanism are unclear. The purpose of this study was to investigate that 1,25VD3 might promote the defensive ability of osseointegration through suppressing AGEs/RAGE in type 2 diabetes mellitus. In animal study, streptozotocin-induced diabetic rats accepted implant surgery, with or without 1,25VD3 intervention for 12 weeks. After killing, the serum AGEs level, bone microarchitecture and biomechanical index of rats were measured systematically. In vitro study, osteoblasts differentiation capacity was analyzed by alizarin red staining, alkaline phosphatase assay and Western blotting, after treatment with BSA, AGEs, AGEs with RAGE inhibitor and AGEs with 1,25VD3. And the expression of RAGE protein was detected to explore the mechanism. Results showed that 1,25VD3 could reverse the impaired osseointegration and mechanical strength, which possibly resulted from the increased AGEs. Moreover, 1,25VD3 could ameliorate AGEs-induced damage of cell osteogenic differentiation, as well as downregulating the RAGE expression. These data may provide a theoretical basis that 1,25VD3 could work as an adjuvant treatment against poor osseointegration in patients with type 2 diabetes mellitus.

DOI:
https://doi.org/10.1530/EC-18-0241
Volume 7: Issue 11,
Pages:
1186–1195 (10 total)
Open access

Sex differences in the prevalence of obesity in 800,000 Chinese adults with type 2 diabetes

Fang Lv, Xiaoling Cai, Chu Lin, Tianpei Hong, Xiaomei Zhang, Zhufeng Wang, Huifang Xing, Guizhi Zong, Juming Lu, Xiaohui Guo, Jing Wu, Leili Gao, Xianghai Zhou, Xueyao Han, and Linong Ji

Aims

To estimate the sex differences in the prevalence of overweight and obesity aged 20–89 in Chinese patients with type 2 diabetes (T2D).

Methods

811,264 patients with T2D from six hospital-based, cross-sectional studies, and 46,053 subjects from the general population were included in our analysis. Prevalence of underweight, overweight, obesity were calculated in each sex.

Results

In patients with T2D, the standardized prevalence of underweight (BMI <18.5 kg/m2), overweight (24 kg/m2 ≤ BMI < 28 kg/m2), and general obesity (BMI ≥28 kg/m2) were 2.2%, 43.2%, and 11.6%, respectively. Similar trend patterns of the prevalence of underweight and overweight were observed in general and T2D population, in males and females with T2D (all P for trend <0.01). In patients with T2D, patients at a younger age and older age were more likely to be underweight. The prevalence of overweight increased first, then stabilized or decreased with age. However, different trend patterns of the prevalence of obesity in males and females were found. In males, the prevalence of obesity decreased first, and then stabilized after 60 years of age. In females, the prevalence of obesity decreased first, then increased after 50 years of age. In the general population, the prevalence of obesity increased with age in females, while, the trend of prevalence of obesity with age in males was not obvious.

Conclusion

Different trends in the prevalence of obesity with age in different sex were found in Chinese patients with T2D.

DOI:
https://doi.org/10.1530/EC-20-0547
Volume 10: Issue 2,
Pages:
139–145 (7 total)
Open access

The age factor in survival of a population cohort of well-differentiated thyroid cancer

Andrea Mazurat, Andrea Torroni, Jane Hendrickson-Rebizant, Harbinder Benning, Richard W Nason, and K Alok Pathak

Well-differentiated thyroid carcinoma (WDTC) represents a group of thyroid cancers with excellent prognosis. Age, a well-recognized risk factor for WDTC, has been consistently included in various prognostic scoring systems. An age threshold of 45 years is currently used by the American Joint Cancer Committee-TNM staging system for the risk stratification of patients. This study analyzes the relationship between the patients' age at diagnosis and thyroid cancer-specific survival in a population-based thyroid cancer cohort of 2115 consecutive patients with WDTC, diagnosed during 1970–2010, and evaluates the appropriateness of the currently used age threshold. Oncological outcomes of patients in terms of disease-specific survival (DSS) and disease-free survival (DFS) were calculated by the Kaplan–Meier method, while multivariable analysis was done by the Cox proportional hazard model and proportional hazards regression for sub-distribution of competing risks to assess the independent influence of various prognostic factors. The mean age of the patients was 47.3 years, 76.6% were female and 83.3% had papillary carcinoma. The median follow-up of the cohort was 122.4 months. The DSS and DFS were 95.4 and 92.8% at 10 years and 90.1 and 87.6% at 20 years, respectively. Multivariable analyses confirmed patient's age to be an independent risk factor adversely affecting the DSS but not the DFS. Distant metastasis, incomplete surgical resection, T3/T4 stages, Hürthle cell histology, and male gender were other independent prognostic determinants. The DSS was not independently influenced by age until the age of 55 years. An age threshold of 55 years is better than that of 45 years for risk stratification.

DOI:
https://doi.org/10.1530/EC-13-0056
Volume 2: Issue 3,
Pages:
154–160 (7 total)
Open access

Activation of CD4+ and CD8+ T-lymphocytes by insulin and GAD in patients with type 1 or 2 diabetes mellitus

Borros Arneth

Background

The origin of autoimmune disease type 1 diabetes is still unknown.

Aim

This study assessed the activation of CD4+ and CD8+ T-lymphocytes by human insulin and human glutamate decarboxylase (GAD) in patients with type 1 or type 2 diabetes mellitus (DM) and healthy volunteers.

Materials and methods

The expression of CD69, a marker of T-lymphocyte activity, was determined in whole blood samples by flow cytometry after 12 h of incubation with or without insulin or GAD. The analysis included samples from 12 type 1 DM patients, 14 type 2 DM patients and 12 healthy volunteers.

Results

Significant increases in the number of activated CD4+ and CD8+ T-lymphocytes following pre-incubation of whole blood samples with human insulin or GAD were observed in samples from patients with type 1 DM, whereas no activation of these cells was detected in samples from either type 2 DM patients or healthy subjects.

Discussion

These results indicated that latent pre-activation of CD4+ and CD8+ T-lymphocytes in response to insulin or GAD epitopes occurred in type 1 DM patients.

Conclusion

These findings suggest that pre-immunization against insulin and/or GAD might be associated with the development of type 1 DM. Alternatively, these results might reflect a non-specific, bystander autoimmune response.

DOI:
https://doi.org/10.1530/EC-17-0230
Volume 6: Issue 8,
Pages:
758–765 (8 total)
Open access

100 YEARS OF VITAMIN D: Dietary intake and main food sources of vitamin D and calcium in Colombian urban adults

Mateo Amaya-Montoya, Daniela Duarte-Montero, Luz D Nieves-Barreto, Angélica Montaño-Rodríguez, Eddy C Betancourt-Villamizar, María P Salazar-Ocampo, and Carlos O Mendivil

Data on dietary calcium and vitamin D intake from Latin America are scarce. We explored the main correlates and dietary sources of calcium and vitamin D in a probabilistic, population-based sample from Colombia. We studied 1554 participants aged 18–75 from five different geographical regions. Dietary intake was assessed by employing a 157-item semi-quantitative food frequency questionnaire and national and international food composition tables. Daily vitamin D intake decreased with increasing age, from 230 IU/day in the 18–39 age group to 184 IU/day in the 60–75 age group (P -trend < 0.001). Vitamin D intake was positively associated with socioeconomic status (SES) (196 IU/day in lowest vs 234 in highest SES, P-trend < 0.001), and with educational level (176 IU/day in lowest vs 226 in highest education level, P-trend < 0.001). Daily calcium intake also decreased with age, from 1376 mg/day in the 18–39 age group to 1120 mg/day in the 60–75 age group (P -trend < 0.001). Calcium intake was lowest among participants with only elementary education, but the absolute difference in calcium intake between extreme education categories was smaller than for vitamin D (1107 vs 1274 mg/day, P-trend = 0.023). Daily calcium intake did not correlate with SES (P -trend = 0.74). Eggs were the main source of overall vitamin D, albeit their contribution decreased with increasing age. Dairy products contributed at least 48% of dietary calcium in all subgroups, mostly from cheese-containing traditional foods. SES and education were the key correlates of vitamin D and calcium intake. These findings may contribute to shape public health interventions in Latin American countries.

DOI:
https://doi.org/10.1530/EC-21-0341
Volume 10: Issue 12,
Pages:
1584–1593 (10 total)
Open access

Impact of age, sex and body mass index on cortisol secretion in 143 healthy adults

Ferdinand Roelfsema, Diana van Heemst, Ali Iranmanesh, Paul Takahashi, Rebecca Yang, and Johannes D Veldhuis

Context

Studies on 24-h cortisol secretion are rare. The impact of sex, age and adiposity on cortisol levels, often restricted to one or a few samples, are well recognized, but conflicting.

Objective

To investigate cortisol dynamics in 143 healthy men and women, spanning 7 decades and with a 2-fold body mass index (BMI) range with different analytic tools.

Setting

Clinical Research Unit.

Design

Cortisol concentrations in 10-min samples collected for 24 h. Outcomes were mean levels, deconvolution parameters, approximate entropy (ApEn, regularity statistic) and 24-h rhythms.

Results

Total 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. Mean 24-h cortisol concentrations were lower in premenopausal women than those in men of comparable age (176 ± 8.2 vs 217 ± 9.4 nmol/L, P = 0.02), but not in subjects older than 50 years. This was due to lower daytime levels in women, albeit similar in the quiescent overnight period. Aging increased mean cortisol by 10 nmol/L per decade during the quiescent secretory phase and advanced the acrophase of the diurnal rhythm by 24 min/decade. However, total 24-h cortisol secretion rates estimated by deconvolution analysis were sex, age and BMI independent. ApEn of 24-h profiles was higher (more random) in premenopausal women than those in men (1.048 ± 0.025 vs 0.933 ± 0.023, P = 0.001), but not in subjects older than 50 years. ApEn peaked during the daytime.

Conclusion

Sex and age jointly determine the 24-h cortisol secretory profile. Sex effects are largely restricted to age <50 years, whereas age effects elevate concentrations in the late evening and early night and advance the timing of the peak diurnal rhythm.

DOI:
https://doi.org/10.1530/EC-17-0160
Volume 6: Issue 7,
Pages:
500–509 (10 total)
Open access

Serum retinol-binding protein 4 levels in polycystic ovary syndrome

Shilpa Lingaiah, Laure Morin-Papunen, Terhi Piltonen, Inger Sundström-Poromaa, Elisabet Stener-Victorin, and Juha S Tapanainen

Objective

Serum levels of retinol-binding protein 4 (RBP4), an adipokine thought to affect systemic insulin sensitivity, were compared between women with polycystic ovary syndrome (PCOS) and non-PCOS controls to evaluate the association of RBP4 with clinical, hormonal and metabolic parameters of PCOS.

Subjects and methods

Serum RBP4 levels were analysed in 278 women with PCOS (age range 18–57 years) and 191 non-PCOS controls (age 20–53 years) by enzyme-linked immunosorbent assay.

Results

Serum levels of RBP4 were increased in women with PCOS compared with control women in the whole population (45.1 ± 24.0 (s.d.) vs 33.5 ± 18.3 mg/L, P < 0.001). Age-stratified analysis showed that serum RBP4 levels were increased in women with PCOS aged ≤30 years compared with controls (47.7 ± 23.5 vs 27.1 ± 10.4 mg/L, P < 0.001), whereas no significant differences were seen in the other age groups. No significant correlations of RBP4 were seen with either steroids or indices of insulin resistance.

Conclusions

Although serum RBP4 levels were increased in younger women with PCOS compared with age-matched non-PCOS controls, RBP4 does not seem to be a good marker of insulin resistance or other metabolic derangements in women with PCOS.

DOI:
https://doi.org/10.1530/EC-19-0116
Volume 8: Issue 6,
Pages:
709–717 (9 total)
Open access

Behavioural phenotyping, learning and memory in young and aged growth hormone-releasing hormone-knockout mice

Sheila Leone, Lucia Recinella, Annalisa Chiavaroli, Claudio Ferrante, Giustino Orlando, Michele Vacca, Roberto Salvatori, and Luigi Brunetti

Background

Growth hormone-releasing hormone (GHRH) plays an important role in brain functions. The aim of this study was to examine cognitive functions and emotional behaviour in a mouse model of isolated GH deficiency due to bi-allelic ablation of the GHRH gene (GHRH knockout, GHRHKO).

Methods

Learning, memory and emotional behaviour were evaluated using a series of validated tests (Morris water maze, eight-arm radial maze, open field, elevated plus maze test, forced swim tests) in 2-, 5- and 12-month-old male mice either homozygous (−/−) or heterozygous (+/−) for the GHRHKO allele.

Results

Compared with age-matched +/− mice, −/− mice showed decreased cognitive performance in Morris water maze and eight-arm radial maze tests. By comparing the effects of aging in each genotype, we observed an age-related impairment in test results in +/− mice, while in −/− mice a significant decline in cognitive function was found only in 12 months compared with 2-month-old mice, but no difference was found between 5 months old vs 2 months old. −/− mice showed increased exploration activity compared to age-matched +/− controls, while both strains of mice had an age-related decrease in exploration activity. When evaluated through open field, elevated plus maze and forced swim tests, −/− mice demonstrated a decrease in anxiety and depression-related behaviour compared to age-matched +/− controls.

Conclusions

Our results suggest that homozygous ablation of GHRH gene is associated with decreased performance in learning and memory tests, possibly linked to increased spontaneous locomotor activity. In addition, we observed an age-related decline in cognitive functions in both genotypes.

DOI:
https://doi.org/10.1530/EC-18-0165
Volume 7: Issue 8,
Pages:
924–931 (8 total)
Open access

Growth and disease burden in children with hypophosphatasia

Wolfgang Högler, Agnès Linglart, Anna Petryk, Priya S Kishnani, Lothar Seefried, Shona Fang, Cheryl Rockman-Greenberg, Keiichi Ozono, Kathryn Dahir, and Gabriel Ángel Martos-Moreno

Objective

Hypophosphatasia, an inborn error of metabolism characterized by impaired bone mineralization, can affect growth. This study evaluated relationships between anthropometric parameters (height, weight, and body mass index) and clinical manifestations of hypophosphatasia in children.

Design

Data from children (aged <18 years) with hypophosphatasia were analyzed from the observational Global Hypophosphatasia Registry.

Methods

Anthropometric parameters were evaluated by age group (<2 years and ≥2 years) at assessment. The frequency of hypophosphatasia manifestations was compared between children with short stature (< percentile) and those with normal stature.

Results

This analysis included 215 children (54.4% girls). Short stature presented in 16.1% of children aged <2 years and 20.4% of those aged ≥2 years at assessment. Among those with available data (n = 62), height was below the target height (mean: −0.66 standard deviations). Substantial worsening of growth (mean delta height z score: −1.45; delta weight z score: −0.68) occurred before 2 years of age, while in those aged ≥2 years, anthropometric trajectories were maintained (delta height z score: 0.08; delta weight z score: 0.13). Broad-ranging hypophosphatasia manifestations (beyond dental) were observed in most children.

Conclusions

Short stature was not a consistent characteristic of children with hypophosphatasia, but growth impairment was observed in those aged <2 years, indicating that hypophosphatasia might affect growth plate activity during infancy. In addition, a broad range of clinical manifestations occurred in those above and below the third percentile for height, suggesting that height alone may not accurately reflect hypophosphatasia disease burden and that weight is less affected than longitudinal growth.

DOI:
https://doi.org/10.1530/EC-22-0240
Volume 12: Issue 5