Role of sex steroids, intrahepatic fat and liver enzymes in the association between <scp>SHBG</scp> and metabolic features

Bonnet, Fabrice; Cephise, Fritz-Line Velayoudom; Gautier, A; Dubois, Séverine; Massart, Catherine; Camara, Alioune; Larifla, Laurent; Balkau, Beverley; Ducluzeau, Pierre-Henri

doi:10.1111/cen.12089

Cited by 27 publications

(30 citation statements)

References 34 publications

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“…In this study, the association between sex steroids and WC was not significant (data not shown) that may suggest that this clinical parameter would not be suitable. In a previous study of dysmetabolic subjects, we found that SHBG level correlated inversely with glucose and lipids levels but that this relationship depended on the intrahepatic fat content, which we did not measure in the present study [36]. Moreover, in our current study, SHBG concentrations correlated inversely with BMI and SBP, and this confirmed the data of previous studies of different ethnic populations [32,37].…”

Section: Discussionsupporting

confidence: 90%

Relationship between Testosterone and Sex Hormone Binding Globulin Concentrations with Cardiometabolic Parameters and Macrovascular Disease in Afro-Caribbean Men with Type 2 Diabetes

2015

Endocrinol Metab Syndr

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Introduction: Low testosterone concentrations have been reported in type 2 diabetes (T2D) and Coronary Artery Disease (CAD). Contrary to diabetes, the prevalence of CAD is lower in Afro-Caribbean (AC) from French West Indies islands than in people from mainland France. However, CAD is a frequent complication of T2D. To evaluate this paradoxical situation, we investigated the prevalence of sex steroids deficiency that might be associated with CAD in AC men with T2D and the relationships with metabolic parameters.

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Section: Discussionsupporting

confidence: 90%

Relationship between Testosterone and Sex Hormone Binding Globulin Concentrations with Cardiometabolic Parameters and Macrovascular Disease in Afro-Caribbean Men with Type 2 Diabetes

2015

Endocrinol Metab Syndr

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“…Mendelian randomisation studies, which are less likely to be confounded than traditional observational studies, have associated low SHBG (Ding et al 2009) but not testosterone (Haring et al 2013) with an increased risk of future diabetes. In cross-sectional studies of men with (Grossmann et al 2008) and without (Bonnet et al 2013) diabetes, SHBG but not testosterone was inversely associated with worse glycaemic control. SHBG may have biological actions beyond serving as a carrier protein for and regulator of circulating sex steroids (Wallace et al 2013).…”

Section: End Organ Deficits Of Androgen Deficiencymentioning

confidence: 86%

Testosterone and glucose metabolism in men: current concepts and controversies

Grossmann¹

2013

Journal of Endocrinology

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A wealth of observational studies show that low testosterone is associated with insulin resistance and with an increased risk of diabetes and the metabolic syndrome. Experimental studies have identified potential mechanisms by which low testosterone may lead to insulin resistance. Visceral adipose tissue is an important intermediate in this relationship. Actions of testosterone or its metabolite oestradiol on other tissues such as muscle, liver, bone or the brain, and body composition-independent effects may also play a role. However, definitive evidence from randomised controlled trials (RCTs) to clarify whether the association of low testosterone with disordered glucose metabolism is causative is currently lacking. It therefore remains possible that this association is due to reverse causation, or simply originates by association with common health and lifestyle factors. RCTs of testosterone therapy in men with or without diabetes consistently show modest metabolically favourable changes in body composition. Despite this, testosterone effects on glucose metabolism have been inconsistent. Recent evidence suggests that the hypothalamic-pituitary-testicular axis suppression in the majority of obese men with metabolic disorders is functional, and may be, at least in part, reversible with weight loss. Until further evidence is available, lifestyle measures with emphasis on weight reduction, treatment of comorbidities and optimisation of diabetic control should remain the first-line treatment in these men. Such measures, if successful, may be sufficient to normalise testosterone levels in men with metabolic disorders, who typically have only modest reductions in circulating testosterone levels.

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“…We also found female-specific changes in ADIPO, GLCE, FETUB and SHBG, which all have functions related to lipid biosynthesis or metabolism [31-34]. In addition to its role in lipid-related pathways, SHBG also serves as the main transport protein for sex steroids such as oestrogen and testosterone [35].…”

Section: Discussionmentioning

confidence: 99%

Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome

et al. 2014

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BackgroundThe higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum.MethodsHere, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS.ResultsMultiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls.ConclusionTaken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment approaches.

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Role of sex steroids, intrahepatic fat and liver enzymes in the association between SHBG and metabolic features

Cited by 27 publications

References 34 publications

Relationship between Testosterone and Sex Hormone Binding Globulin Concentrations with Cardiometabolic Parameters and Macrovascular Disease in Afro-Caribbean Men with Type 2 Diabetes

Relationship between Testosterone and Sex Hormone Binding Globulin Concentrations with Cardiometabolic Parameters and Macrovascular Disease in Afro-Caribbean Men with Type 2 Diabetes

Testosterone and glucose metabolism in men: current concepts and controversies

Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome

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