Testosterone and type 2 diabetes

Grossmann, Mathis; Gianatti, Emily J; Zajac, Jeffrey D

doi:10.1097/med.0b013e32833919cf

Cited by 98 publications

(76 citation statements)

References 71 publications

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“…For example, in a recent prospective cohort study of men presenting for liver transplantation, low testosterone predicted mortality independently of the model of end-stage liver disease score, the standard score used to prioritise the allocation of liver transplants . It is evident from multiple studies that low testosterone identifies men with an adverse metabolic phenotype (Grossmann et al 2010). Diabetic men with low testosterone are significantly more likely to be obese or insulin resistant.…”

Section: End Organ Deficits Of Androgen Deficiencymentioning

confidence: 99%

“…In prospective studies, reviewed in detail elsewhere (Grossmann et al 2010) the inverse association of low testosterone with metabolic syndrome or diabetes is less consistent for free testosterone compared with total testosterone. This is because of the confounding effects of SHBG, itself being a strong associate of insulin resistance (Wallace et al 2013).…”

Section: End Organ Deficits Of Androgen Deficiencymentioning

confidence: 99%

“…Some, but not all uncontrolled studies, reviewed in Grossmann et al (2010) have suggested beneficial effects of testosterone therapy on glucose metabolism. More recently, two observational studies, one in US Veterans (Shores et al 2012) the other in diabetic men from the UK (Muraleedharan et al 2013) have been reported.…”

Section: Testosterone Treatment In Men With Metabolic Disordersmentioning

confidence: 99%

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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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Section: End Organ Deficits Of Androgen Deficiencymentioning

confidence: 99%

Section: End Organ Deficits Of Androgen Deficiencymentioning

confidence: 99%

Section: Testosterone Treatment In Men With Metabolic Disordersmentioning

confidence: 99%

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Testosterone and glucose metabolism in men: current concepts and controversies

Grossmann¹

2013

Journal of Endocrinology

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“…In women, it is well known that hyperandrogenism is often associated with increased intra-abdominal fat accumulation and the metabolic syndrome (as for the case of polycystic ovary syndrome; Gambineri et al 2009), and the decline of estrogen after menopause is known to determine an increase in intraabdominal fat mass (Lobo 2008). In men, testosterone deficiency in hypogonadic individuals is associated with a significant change in body composition (especially featured by an increase in fat mass) and with the frequent presence of dysmetabolisms (Barrett-Connor 1992, Barud et al 2002, Grossmann et al 2010, Traish et al 2011. Testosterone replacement therapy in patients with reduced testosterone levels has been shown to produce a significant metabolic amelioration, not only related to body weight but also related to the glucose and lipid profile (Traish et al 2011).…”

Section: Brown Adipose Tissue and Obesitymentioning

confidence: 99%

Role of sex hormones in modulation of brown adipose tissue activity

Quarta

Mazza²,

Pasquali³

et al. 2012

Journal of Molecular Endocrinology

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The recent demonstration that metabolically active brown adipose tissue (BAT) is present with a high prevalence in humans undoubtedly represents one of the major advancements in the field of metabolic research in the last few years. The increasing interest in BAT is justified by preclinical observations highlighting an important role of this tissue in energy dissipation and metabolic clearance of substrates from the blood. These findings imply that stimulation of BAT activity may represent a new therapeutic approach for obesity and associated comorbidities. However, before proposing BAT as a target organ for therapeutics in a clinical setting, many further notions about BAT function and modulation need to be explored. Keeping in mind the importance of sex dimorphism in energy metabolism control under physiological and pathological conditions, sex hormones may play a relevant role in the regulation of BAT activity in both males and females. Much of the evidence acquired in the past supports the concept of an important role for different sex hormones in BAT thermogenesis and indicates that this tissue mediates the ability of sex hormones to modulate energy balance. These findings make it plausible that a modified interaction between BAT and sex hormones may contribute to the development and the maintenance of obesity and associated metabolic complications.Journal of Molecular Endocrinology (2012) 49, R1-R7

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“…Accordingly, an increase in muscle mass and a reciprocal decrease in fat mass have been reported in randomized, placebo-controlled trials of testosterone therapy in elderly nondiabetic men (1, 2, 3, 4). However, the changes in body composition are modest, and this may explain why only a few, but not all, of these studies have found a positive effect on the measures of insulin sensitivity (1, 4,5). A better understanding of the mechanisms involved in androgen action is needed to establish to what extent testosterone deficiency causally contributes to insulin resistance and type 2 diabetes in elderly men, and to clarify potential beneficial effects of testosterone replacement therapy on insulin sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone

Petersson

Christensen

Kristensen

et al. 2014

European Journal of Endocrinology

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Objective: Recent studies have indicated that serum testosterone in aging men is associated with insulin sensitivity and expression of genes involved in oxidative phosphorylation (OxPhos), and that testosterone treatment increases lipid oxidation. Herein, we investigated the effect of testosterone therapy on regulators of mitochondrial biogenesis and markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels. Methods: Skeletal muscle biopsies were obtained before and after treatment with either testosterone gel (nZ12) or placebo (nZ13) for 6 months. Insulin sensitivity and substrate oxidation were assessed by euglycemic-hyperinsulinemic clamp and indirect calorimetry. Muscle mRNA levels and protein abundance and phosphorylation of enzymes involved in mitochondrial biogenesis, OxPhos, and lipid metabolism were examined by quantitative real-time PCR and western blotting. Results: Despite an increase in lipid oxidation (P!0.05), testosterone therapy had no effect on insulin sensitivity or mRNA levels of genes involved in mitochondrial biogenesis (PPARGC1A, PRKAA2, and PRKAG3), OxPhos (NDUFS1, ETFA, SDHA, UQCRC1, and COX5B), or lipid metabolism (ACADVL, CD36, CPT1B, HADH, and PDK4). Consistently, protein abundance of OxPhos subunits encoded by both nuclear (SDHA and UQCRC1) and mitochondrial DNA (ND6) and protein abundance and phosphorylation of AMP-activated protein kinase and p38 MAPK were unaffected by testosterone therapy. Conclusion: The beneficial effect of testosterone treatment on lipid oxidation is not explained by increased abundance or phosphorylation-dependent activity of enzymes known to regulate mitochondrial biogenesis or markers of OxPhos and lipid metabolism in the skeletal muscle of aging men with subnormal bioavailable testosterone levels.

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Testosterone and type 2 diabetes

Cited by 98 publications

References 71 publications

Testosterone and glucose metabolism in men: current concepts and controversies

Testosterone and glucose metabolism in men: current concepts and controversies

Role of sex hormones in modulation of brown adipose tissue activity

Effect of testosterone on markers of mitochondrial oxidative phosphorylation and lipid metabolism in muscle of aging men with subnormal bioavailable testosterone

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