BACKGROUND BACKGROUND: Type 2 diabetes mellitus (DM2) in men is associated with a high incidence of hypogonadism. Testosterone is a steroid hormone and one of the final metabolites of steroidogenesis, which causes interest in assessing the content of key steroid hormones, their precursors and metabolites in hypogonadal and eugonadal men with T2DM. AIMS AIMS: Assessment of the features of steroidogenesis in men with hypogonadism in T2DM using tandem mass spectrometry. MATERIALS AND METHODS MATERIALS AND METHODS: A full-design, cross-sectional, screening, single-center, non-interventional study included men with T2DM, who were he was treated in Endocrinology Research Centre, Moscow. The study was conducted from October 2021 to January 2022. Medical history assessment, physical examination with determination of body mass index (BMI), measurement of key steroid hormones, their precursors and metabolites by isotope dilution liquid chromatography/tandem mass spectrometry, glycated hemoglobin (HbA1c) were performed. The groups were compared using the Mann-Whitney U-test for quantitative indicators and χ² with Yates’ correction for qualitative ones. Correlation analysis was performed by the Spearman correlation method. When determining the criterion of statistical significance, the Bonferroni correction was applied. RESULTS RESULTS: Patients with hypogonadism had statistically significantly more pronounced obesity compared with eugonadal men. In a comparative analysis of patients, depending on the presence of hypogonadism, there were statistically significantly lower levels of androgen precursors 17-hydroxypregnenolone and 17-hydroxyprogesterone in hypogonadal men. At the same time, a positive statistically significant correlation was found between total testosterone and 17-hydroxyprogesterone. In addition, 17-hydroxyprogesterone, although to a lesser extent, but positively correlated with other androgens - androstenedione (r=0,328; p<0,001) and dehydroepiandrosterone (r=0,183; p=0,004). >< 0,001) and dehydroepiandrosterone (r=0,183; p=0,004). CONCLUSIONS CONCLUSIONS: In this investigation the prevalence of male hypogonadism in type 2 diabetes, determined by high-precision tandem mass spectrometry, was 69,5%. There was no effect of the disease on the mineralocorticoid and glucocorticoid links of adrenal steroidogenesis. Hypogonadism was associated with decreased levels of a number of testosterone precursors. The most significant of them was 17-hydroxyprogesterone, which can be considered as a marker of testicular steroidogenesis.

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Features of steroidogenesis in men with hypogonadism and type 2 diabetes

BACKGROUND: Male hypogonadism is associated with type 2 diabetes mellitus (T2DM), therefore, it is of interest to study its frequency. The clinical symptoms of hypogonadism are not specific, and laboratory diagnostics is the basis for its detection. The optimal method for this diagnostics is isotope dilution liquid chromatography/tandem mass spectrometry, which was used in our study. AIMS: Assessment of the incidence and aggravating factors of male hypogonadism in type 2 diabetesMATERIALS AND METHODS: A full-design, cross-sectional, screening, single-center, non-interventional study included men with T2DM, who were he was treated in Endocrinology Research Centre, Moscow. The study was conducted from October 2021 to January 2022. Medical history assessment, physical examination with determination of body mass index (BMI), measurement estimation of total testosterone by isotope dilution liquid chromatography/tandem mass spectrometry, glycated hemoglobin (HbA1c) and lipid profiles were performed. The groups were compared using the Mann-Whitney U-test for quantitative indicators and χ² with Yates’ correction for qualitative ones. Differences were considered statistically significant with p0,05.RESULTS: Hypogonadism was detected in 355 (70.3%) men with T2DM. Patients with hypogonadism had statistically significantly higher BMI, worse glycemic control, lower HDL levels, and higher triglycerides than eugonadal men. An additional comparative analysis among non-obese individuals showed the presence of statistically significant differences in the level of HbA1c (higher in hypogonadal men) and HDL (lower in hypogonadal men). An analysis of hypogonadal patients depending on the presence of obesity showed statistically significant differences between groups in the level of total testosterone (lower in obese men) and triglycerides (higher in obese men).CONCLUSIONS: The prevalence of male hypogonadism in type 2 diabetes was 70,3%. Its development was associated with obesity and poor glycemic control.

The incidence and aggravating factors of male hypogonadism in type 2 diabetes

Background: Male hypogonadism is associated with type 2 diabetes mellitus (T2DM), therefore, it is of interest to study its clinical and epidemiological characteristics. These data are published, but their fragmentation and small sample sizes are a problem. A summary assessment of the combined primary data of the conducted studies will provide sufficient representativeness and will allow to extrapolate the results to the general Russian population with T2DM.Aim: Assessment of the clinical and epidemiological characteristics and aggravating factors of male hypogonadism in T2DM in Russia.Materials and methods: A Combining primary data (anamnesis, anthropometric indicators, laboratory tests) of full-design, cross-sectional, screening studies of hypogonadism in men with T2DM conducted on the territory of the Russian Federation in the period from 2005 to 2022. The groups were compared using the Mann-Whitney U-test for quantitative indicators and χ² with Yates’ correction for qualitative ones. Differences were considered statistically significant with p <0,05. The groups were compared using the Mann-Whitney U-test and χ² with Yates correction. Differences were considered statistically significant at p<0.05.Results: Hypogonadism was detected in 893 of 1576 men (56,7%) with T2DM. Patients with hypogonadism were statistically significantly older, had higher body mass index (BMI), worse glycemic control than eugonadal men. There was ­statistically significantly higher prevalence of macroangiopathies and polyneuropathy in hypogonadal patients.Conclusion: The prevalence of male hypogonadism in T2DM 56,7%. Its development is due to age, obesity, worse glycemic control. Hypogonadism syndrome is associated with the development of diabetic macroangiopathy and polyneuropathy. Severe violation of glycemic control (glycated hemoglobin (HbA1c) 10% or more) significantly reduces testosterone production and increases the prevalence of hypogonadism.

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Clinical and epidemiological characteristics of male hypogonadism in type 2 diabetes in Russia: combined analysis of study data for the period 2005–2022

Testosterone may be a possible modifiable risk factor for open-angle glaucoma (OAG) and intraocular pressure (IOP), but evidence has been scarce and conflicting. In this study we evaluated the association of testosterone and its genetic predisposition with incident (i) OAG, IOP, retinal nerve fiber layer (RNFL), and ganglion cell-inner plexiform layer (GCL +).Participants aged 45-100 years were derived from the prospective, population-based Rotterdam Study. Ophthalmic examinations and serum testosterone measurements (including bioavailable and free testosterone) were performed from 1991 onwards. Follow-up took place every 4-5 years. A total of 187 out of 7898 participants were diagnosed with incident (i) OAG during follow-up. Genotyping was performed in 165 glaucoma cases and 6708 controls. We calculated sex-specific weighted genetic risk scores (GRS) for total and bioavailable testosterone. Associations with iOAG were analyzed using multivariable logistic regression. Associations with IOP, RNFL, and GCL + were analyzed with multivariable linear regression. Analyses were stratified on sex and adjusted for at least age, body mass index, and follow-up duration.In men, testosterone was not associated with iOAG. However, the GRS for higher total testosterone was associated with an increased iOAG risk (odds ratio [OR] with 95% confidence interval [95% CI]: 2.48 [1.18; 5.22], per unit). In women, higher values of bioavailable testosterone (2.05 [1.00; 4.18] per nmol/L) and free testosterone (1.79 [1.00; 3.20] per ng/dL) were significantly associated with increased risk of iOAG. Moreover, the GRS for higher bioavailable testosterone was associated with an increased iOAG risk (2.48 [1.09; 5.65], per unit). Higher bioavailable and free testosterone were adversely associated with IOP (0.58 [0.05; 1.10] per nmol/L and 0.47 [0.04; 0.90] per ng/dL). Higher total testosterone was inversely associated with peripapillary RNFL and GCL + (Beta [95% CI]: - 3.54 [- 7.02; - 0.06] per nmol/L and - 2.18 [- 4.11; - 0.25] per nmol/L, respectively).In women, higher testosterone levels increased the risk of iOAG. Both IOP-dependent and IOP-independent mechanisms may underlie this association. Managing testosterone levels may be particularly relevant for the prevention of neurodegeneration in the eye. Future research should confirm these findings. 

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Higher testosterone is associated with open-angle glaucoma in women: a genetic predisposition?

Introduction Hypogonadotropic hypogonadism is a common disorder associated with type 2 diabetes. Hypogonadotropic hypogonadism in type 2 diabetic patients requires further assessment to understand the etiology, and the possible consequences, complications, and treatment This study aims to highlight the testosterone level in type 2 diabetes mellitus (DM). Moreover, it further emphasizes the association of testosterone with the duration of DM. Materials and method This case-control survey was conducted from September 2020 to March 2021 in the outpatient department of internal medicine in a tertiary care hospital in Pakistan. The experiment group included 200 diabetic male participants aged between 30 and 69 years. In the control group, 200 participants without DM were enrolled in the study. The venous blood sample was collected via phlebotomy and sent to the laboratory to test for total testosterone level. Results The mean total testosterone level was significantly lower in diabetic patients compared to the non-diabetic patients (8.9 ± 5.1 mmol/L vs. 14.1 ± 7.2 mmol/L; p-value: <0.0001) and the prevalence of androgen deficiency was significantly higher in diabetic patients compared to non-diabetic patients (45.5% vs. 20.5%; p-value: <0.00001). For each age group, the mean total testosterone level was significantly higher in the diabetic group compared to the non-diabetic group. There was a significant decline in mean total testosterone level as the duration of diabetes increased (p-value: 0.01). Conclusion Strong interlink between type 2 DM and low testosterone level has once again highlighted the importance of a broader approach toward men presenting in the diabetic clinic and provided a huge ground for prescribing testosterone replacement therapy in hypogonadal men with DM.

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Anoosha Khan

Papers

Comparison of Testosterone Levels in Patients With and Without Type 2 Diabetes.