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Nikolaj Rittig Department of Internal Medicine and Endocrinology (MEA) and Medical Research Laboratory, Aarhus University Hospital, Aarhus C, Denmark

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Mads Svart Department of Internal Medicine and Endocrinology (MEA) and Medical Research Laboratory, Aarhus University Hospital, Aarhus C, Denmark

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Niels Jessen Research Laboratory for Biochemical Pathology, Institute for Clinical Medicine, Aarhus University Hospital, Aarhus C, Denmark

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Niels Møller Department of Internal Medicine and Endocrinology (MEA) and Medical Research Laboratory, Aarhus University Hospital, Aarhus C, Denmark

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Holger J Møller Department of Clinical Biochemistry Aarhus University Hospital, Aarhus C, Denmark

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Henning Grønbæk Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus C, Denmark

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Background

Macrophage activation determined by levels of soluble sCD163 is associated with obesity, insulin resistance, diabetes mellitus type 2 (DM2) and non-alcoholic fatty liver disease (NAFLD). This suggests that macrophage activation is involved in the pathogenesis of conditions is characterised by adaptions in the lipid metabolism. Since sCD163 is shed to serum by inflammatory signals including lipopolysaccharides (LPS, endotoxin), we investigated sCD163 and correlations with lipid metabolism following LPS exposure.

Methods

Eight healthy male subjects were investigated on two separate occasions: (i) following an LPS exposure and (ii) following saline exposure. Each study day consisted of a four-hour non-insulin-stimulated period followed by a two-hour hyperinsulinemic euglycemic clamp period. A 3H-palmitate tracer was used to calculate the rate of appearance (Rapalmitate). Blood samples were consecutively obtained throughout each study day. Abdominal subcutaneous adipose tissue was obtained for western blotting.

Results

We observed a significant two-fold increase in plasma sCD163 levels following LPS exposure (P < 0.001), and sCD163 concentrations correlated positively with the plasma concentration of free fatty acids, Rapalmitate, lipid oxidation rates and phosphorylation of the hormone-sensitive lipase at serine 660 in adipose tissue (P < 0.05, all). Furthermore, sCD163 concentrations correlated positively with plasma concentrations of cortisol, glucagon, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 (P < 0.05, all).

Conclusion

We observed a strong correlation between sCD163 and stimulation of lipolysis and fat oxidation following LPS exposure. These findings support preexisting theory that inflammation and macrophage activation play a significant role in lipid metabolic adaptions under conditions such as obesity, DM2 and NAFLD.

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Zhaoxiang Liu Department of Endocrinology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China

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Mingqiang Zhang Department of Respiratory and Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China

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Xiaohu Shi Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China

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Wenhui Zhao Department of Endocrinology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China

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Chenxiang Cao Department of Endocrinology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China

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Lixia Jin Department of Endocrinology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China

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Yanlei Wang Department of Endocrinology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China

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Jianzhong Xiao Department of Endocrinology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China

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Objectives

The activation of immune cells plays a significant role in the progression of type 2 diabetes. This study aimed to investigate the potential role of myeloid-derived suppressor cells (MDSCs) and T-regulatory cells (Tregs) in type 2 diabetes.

Methods

A total of 61 patients diagnosed with type 2 diabetes were recruited. Clinical characteristics were reviewed and peripheral blood samples were collected. We calculated the percentage of different cells. Frequencies of MDSC subsets refered to the percentage of G-MDSCs (CD15+CD33+CD11b+CD14-HLA-DR-/low) in CD45 positive cells and the percentage of M-MDSCs (CD14+CD15-CD11b+CD33+HLA-DR-/low) in lymphocytes plus monocytes.

Results

Frequencies of programmed cell death ligand 1-positive granulocytic MDSCs (PD-L1+ G-MDSCs), programmed cell death ligand 2-positive monocytic MDSCs (PD-L2+ M-MDSCs), PD-L2+ G-MDSC, and programmed cell death protein 1-positive Tregs (PD-1+Tregs) were decreased in patients with type 2 diabetes. The frequency of PD-1+ Tregs was positively related to PD-L2+ M-MDSCs (r= 0.357, P = 0.009) and negatively related to HbA1c (r = -0.265, P = 0.042), fasting insulin level (r = −0.260, P = 0.047), and waist circumference (r = −0.373, P = 0.005).

Conclusions

Decreased PD-L2+ M-MDSCs and PD-1+ Tregs may promote effector T cell activation, leading to chronic low-grade inflammation in type 2 diabetes. These findings highlight the contribution of MDSCs and Tregs to the immunopathogenesis of type 2 diabetes and suggest their potential as targets for new therapeutic approaches.

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Clara Lundetoft Clausen Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark

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Trine Holm Johannsen Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Niels Erik Skakkebæk Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Hanne Frederiksen Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Thomas Benfield Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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In the context of severe coronavirus disease 2019 (COVID-19) illness, we examined endogenous glucocorticoid concentrations, steroidogenic enzyme activity, and their correlation with inflammation and patient outcomes. This observational study included 125 hospitalized COVID-19 patients and 101 healthy individuals as a reference group. We utilized LC-MS to assess serum concentrations of 11-deoxycortisol, cortisol, and cortisone, as well as activities of steroidogenic enzymes (11β-hydroxylase and 11β-hydroxysteroid-dehydrogenase type 1). Cox proportional hazards regression analysis and competing risk analysis were employed to analyze associations between glucocorticoid concentrations and outcomes, adjusting for relevant factors. In patients with COVID-19, cortisol concentrations were higher and cortisone concentrations were lower compared to the reference group, while 11-deoxycortisol concentrations were similar. Steroidogenic enzyme activity favored cortisol production. Correlations between glucocorticoid concentrations and inflammatory markers were low. A doubling in concentrations cortisol, was associated with increased 90-day mortality and mechanical ventilation (HR: 2.40 95% CI: (1.03–5.59) , P = 0.042 and HR: 3.83 (1.19–12.31), P = 0.024). A doubling in concentrations of 11-deoxycortisol was also associated to mortality (HR: 1.32 (1.05–1.67), P = 0.018), whereas concentrations of cortisone were associated with mechanical ventilation (HR: 5.09 (1.49–17.40), P = 0.009). In conclusion, serum concentrations of glucocorticoid metabolites were altered in patients hospitalized with severe COVID-19, and steroidogenic enzyme activity resulting in the conversion of cortisone to biologically active cortisol was preserved, thus not favoring critical-illness-related corticosteroid insufficiency at the enzymatic level. Glucocorticoid release did not counterbalance the hyperinflammatory state in patients with severe COVID-19. High serum concentrations of 11-deoxycortisol and cortisol were associated with 90-day mortality, and high serum concentrations of cortisol and cortisone were associated with mechanical ventilation.

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Xiaowen Zhang Department of Endocrinology, Drum Tower Hospital affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases, Endocrine and Metabolic Disease Medical Center, Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, China

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Chen Han Department of Endocrinology, Drum Tower Hospital affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases, Endocrine and Metabolic Disease Medical Center, Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, China
Department of Endocrinology and Metabolism, Drum Tower Clinical Medical College, Southeast University, Nanjing, China

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Hongwei Wang State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, Nanjing, China

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Xinghong Sun Department of Ophthalmology, Nanjing University Medical School Affiliated Drum Tower Hospital, Nanjing, China

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Xin Dou Department of Radiology, Nanjing University Medical School Affiliated Drum Tower Hospital, Nanjing, China

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Xueying He Department of Radiology, Nanjing University Medical School Affiliated Drum Tower Hospital, Nanjing, China

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Di Wu Department of Radiology, Southeast University Medical School Affiliated Zhongda Hospital, Nanjing, China

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Shanmei Shen Department of Endocrinology, Drum Tower Hospital affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases, Endocrine and Metabolic Disease Medical Center, Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, China

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Dalong Zhu Department of Endocrinology, Drum Tower Hospital affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases, Endocrine and Metabolic Disease Medical Center, Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, China

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Xinlin Zhang Department of Cardiology, Nanjing University Medical School Affiliated Drum Tower Hospital, Nanjing, China

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Yan Bi Department of Endocrinology, Drum Tower Hospital affiliated to Nanjing University Medical School, Branch of National Clinical Research Centre for Metabolic Diseases, Endocrine and Metabolic Disease Medical Center, Drum Tower Hospital affiliated to Nanjing University Medical School, Nanjing, China

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Thyroid eye disease (TED) is the major extrathyroidal manifestation of Graves’ disease (GD). Treatment choice is based on clinical activity and severity of TED, as evaluated with clinical activity score (CAS) and magnetic resonance (MR) imaging. We aimed to determine the relationship between neutrophil-to-lymphocyte ratio (NLR), a readily available indicator of systemic inflammation, and clinical and MR imaging parameters in TED patients. Eighty-seven consecutive TED patients were included. The average signal intensity ratio (SIR), average extraocular muscle (EOM) diameter, and proptosis of the study eye were extracted from MR images. A baseline NLR ≥ 2.0 was recorded in 37 (42.5%) patients and NLR < 2.0 in 50 (57.5%) patients. TED patients with NLR ≥ 2.0 were older, had a higher CAS, average SIR, average EOM diameter and proptosis, and a lower serum thyrotrophin receptor antibody level than patients with NLR < 2.0 (all P < 0.05). All MR parameters showed significant correlation with CAS (P < 0.05). NLR correlated significantly with CAS (P = 0.001), average SIR (P = 0.004), average EOM diameter (P = 0.007), and proptosis (P = 0.007). Multiple regression revealed a significant correlation between NLR and CAS (P = 0.001), average SIR (P = 0.029), and proptosis (P = 0.037). Cox regression analysis showed that a high NLR at baseline was associated with a worse clinical outcome of TED (hazard ratio 3.7, 95% CI 1.22–11.2, P = 0.02), at a median follow-up of 25 months. In conclusion, NLR was correlated with CAS and MR imaging parameters and was associated with a worse clinical outcome of TED at follow-up in patients with TED. Additional prospective studies are needed to validate our findings.

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Claire L Wood Department of Paediatric Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK

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Kieren G Hollingsworth Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK

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Edrina Bokaie Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK

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Eric Hughes Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK

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Robert Muni-Lofra Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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Anna Mayhew Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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Rod T Mitchell MRC Centre for Reproductive Health, The University of Edinburgh, Queens Medical Research Institute, Edinburgh, UK

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Michela Guglieri Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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Joseph McElvaney Department of Paediatric Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK

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Timothy D Cheetham Department of Paediatric Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK

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Volker Straub Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK

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Glucocorticoids (GCs) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause pubertal delay. Pubertal induction with testosterone is recommended but longer-term outcome is unknown.

Objective

To assess hypothalamic–pituitary–gonadal axis, muscle volume and function 5 years after pubertal induction.

Methods

A prospective observational follow-up of a clinical study was conducted. 15 GC-treated males with DMD were treated with incremental testosterone for 2 years (end of regimen +2 years) then evaluated at +2.5 years and +5 years (final follow-up ~3 years after last injection). Data collected included testicular volume (TV), gonadotrophin, testosterone, inhibin B, muscle function, and limb muscle MRI.

Results

Participants were 18.7 years (s.d. 1.6) at the final follow-up and had been on GC for 11.2 years (s.d. 2.2). Testosterone levels were similar at +2.5 years (8.6 nmol/L (s.d. 3.4) and 5 years (11.0 nmol/L (s.d. 6.1). TV increased from 2.8 mL (s.d. 0.9) at +2 years to 7.1 mL (s.d. 1.8) then 10.6 mL (s.d. 3.5) at +2.5 years and +5.0 years (P < 0.001). Inhibin B levels increased from 55.6 pg/mL (s.d. 47.0) at baseline to 158.2 pg/mL (s.d.87.6), P =0.004 at 5 years but remained lower than reference values (mean 305 pg/mL). Muscle contractile bulk decreased.

Interpretation

Pubertal induction with testosterone in DMD is associated with HPG axis activation and ongoing increases in inhibin B, TV, and testosterone concentrations. Some patients have normal levels which is promising regarding future fertility. Given the beneficial impact of testosterone on bone health, muscle, and well-being, monitoring testosterone levels in this population and supplementation of sub-optimal levels is important.

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Xinyuan Zhang Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China

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Suiyan Li School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China

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Hongwei Liu Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Huai Bai Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Qingqing Liu Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Chunyi Yang Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Ping Fan Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China

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Oxidative stress and metabolic disorders are involved in the pathogenesis of polycystic ovary syndrome (PCOS). Heme oxygenase 2 (HMOX2) plays a critical role in preserving heme metabolism as well as in modulating glycolipid metabolism, oxidative stress, and inflammation. This study examined the correlation between HMOX2 G554A (rs1051308) and A-42G (rs2270363) genetic variants with the risk of PCOS and assessed the effects of these genotypes on clinical, hormonal, metabolic, and oxidative stress indices using a case–control design that included 1014 patients with PCOS and 806 control participants. We found that the allelic and genotypic frequencies of the HMOX2 G554A and A-42G polymorphisms were comparable between the PCOS and control groups in Chinese women (P > 0.05). Nevertheless, it was discovered that patients with the AA or AG genotype of A-42G polymorphism had notably elevated levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (apo)B, and/or apoB/apoA1 ratio than those with the GG genotypes (P < 0.05). Patients with the GG or AG genotype of G554A polymorphism had elevated serum levels of LH, FSH, E2, LH/FSH ratio, TC, HDL-C, LDL-C, apoB, and/or apoB/apoA1 ratio and lower 2-h glucose concentration compared with those with the AA genotype (P < 0.05). Our findings indicate a potential association between the genetic variants and endocrine abnormalities in the reproductive system and metabolic irregularities in glycolipid levels in patients, thus suggesting their potential role in the pathogenesis of PCOS.

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Sebastião Freitas de Medeiros Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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Márcia Marly Winck Yamamoto Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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Matheus Antônio Souto de Medeiros Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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Bruna Barcelo Barbosa Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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José Maria Soares Junior Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Edmund Chada Baracat Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Objective

To verify whether aging can modify the clinical and biochemical characteristics of women with polycystic ovary syndrome (PCOS).

Material and methods

This observational cross-sectional study was conducted at the reproductive endocrinology clinics of Julio Muller University Hospital and Tropical Institute of Reproductive Medicine in Cuiabá, MT, Brazil, between 2003 and 2017. Both, 796 PCOS and 444 non-PCOS normal cycling women underwent the same examination. PCOS was diagnosed using the Rotterdam criteria as recommended for adolescent and adult subjects. Anthropometric, metabolic, and endocrinological modifications with aging were initially examined in the two groups: control and PCOS. Further analyses were performed after a 5-year age stratification of data throughout the reproductive period. All participants signed a consent form approved by the local ethical committee.

Results

Biomarkers of adiposity were more remarkable in African descendant PCOS women. Body weight, waist/hip ratio, fat mass, and BMI were higher in PCOS women and tended to increase at all 5 age-strata, between ≤19 and 35 years of age. Serum androgen levels decreased with aging, markedly in PCOS subjects (P < 0.01 for all age-strata comparisons), but remained elevated when compared with the levels found in controls. Carbohydrate markers, triglycerides, and total cholesterol tended to increase over time in PCOS (P < 0.01 for all age-strata comparisons). Total cholesterol also tended to increase with age in non-PCOS women (P = 0.041).

Conclusion

The present study has shown that the advancing age influences many features of PCOS women. Biochemical hyperandrogenism, the core criterion recommended in the current systems to define the syndrome, showed statistically significant tendencies to decrease with aging progression but did not normalize. The use of age-adjusted features for the diagnosis of PCOS are recommended.

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Tingting Jia Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

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Ya-nan Wang Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

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Dongjiao Zhang Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

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Xin Xu Department of Implantology, School of Stomatology, Shandong University, Jinan, People’s Republic of China
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China

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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.

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Luca Boeri Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
Department of Urology, Foundation IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

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Paolo Capogrosso Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Walter Cazzaniga Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Edoardo Pozzi Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Luigi Candela Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Federico Belladelli Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Davide Oreggia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Eugenio Ventimiglia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Nicolò Schifano Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Giuseppe Fallara Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Marina Pontillo Laboratory Medicine Service, IRCCS Ospedale San Raffaele, Milan, Italy

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Costantino Abbate Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Emanuele Montanari Department of Urology, Foundation IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

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Francesco Montorsi Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Andrea Salonia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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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.

Open access
Borros Arneth Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, University Hospital of the Universities of Giessen and Marburg, UKGM, Justus Liebig University, Giessen, Giessen, Germany

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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.

Open access