MR spectroscopy of hepatic fat and adiponectin and leptin levels during testosterone therapy in type 2 diabetes: a randomized, double-blinded, placebo-controlled trial

Magnussen, Line Velling; Andersen, Poul Erik; Diaz, Anabel; Ostojić, Jelena; Højlund, Kurt; Hougaard, David M.; Christensen, Anders Nymark; Nielsen, Troels Halfeld; Andersen, Marianne

doi:10.1530/eje-17-0071

Cited by 26 publications

(26 citation statements)

References 58 publications

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“…It remains unclear which method would fit the natural relations most optimally. Sex hormones may affect leptin concentrations, which has been suggested in studies on exogenous sex hormone administration in transgender persons [34,35].…”

Section: Discussionmentioning

confidence: 99%

Sex differences in body fat distribution are related to sex differences in serum leptin and adiponectin

et al. 2018

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It is debated whether sex differences in adiponectin and leptin are due to sex differences in body fat distribution. In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, associations of measures of body fat and sex with serum adiponectin and leptin concentrations were examined using linear regression analysis (n = 6494, VAT: n = 2516). Sex differences were additionally adjusted for the measure of body fat that was most strongly associated with adiponectin or leptin concentrations. Median adiponectin concentrations in women and men were 10.5 mg/L (IQR, interquartile range: 7.7-13.9) and 6.1 mg/L (IQR: 4.5-8.2), mean difference 4.6 mg/L (95% CI: 4.3, 4.9). Median leptin concentrations in women and men were 19.2 μg/L (IQR: 11.5-30.0) and 7.1 μg/L (IQR: 4.6-11.1), mean difference 15.1 μg/L (95% CI: 14.4, 15.8). VAT was most strongly associated with adiponectin, total body fat percentage was most strongly associated with leptin. After adjustment for VAT, women had 3.8 mg/L (95% CI: 3.3, 4.3) higher adiponectin than men. After adjustment for total body fat percentage, leptin concentrations in women were 0.4 μg/L lower than in men (95% CI: -1.2, 2.0). One genetic variant (rs4731420) was associated with extreme leptin concentrations (>100 μg/L) in women: odds ratio 2.8 (95% CI: 1.7, 4.6). Total body fat percentage was strongly associated with leptin concentrations. Higher leptin concentrations in women than in men were completely explained by differences in total body fat percentage. Visceral fat was associated with adiponectin concentrations, and did not completely explain higher adiponectin concentrations in women than in men.

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Section: Discussionmentioning

confidence: 99%

Sex differences in body fat distribution are related to sex differences in serum leptin and adiponectin

et al. 2018

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“…Visceral adipose tissue is more strongly linked to insulin resistance than subcutaneous adipose tissue is. Though various RCTs have consistently proved that TRT can reduce total body fat mass, 77,82–83,102–103 its effects on regional fat redistribution are not consistently proven; some studies have shown a reduction in visceral adipose tissue 103–104 whereas others have not. 79,102,105 These inconsistencies may be due to small sample sizes or imprecise methodology to quantify visceral adipose tissue like dual-energy X-ray absorptiometry or ultrasound.…”

Section: Areas Of Uncertaintymentioning

confidence: 99%

Male Obesity-related Secondary Hypogonadism – Pathophysiology, Clinical Implications and Management

Fernandez

Chacko²,

Pappachan

2019

European Endocrinology

106

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“…In one 24‐week study of 39 men with a bioavailable testosterone of 7.3 nmol/L (mean age 60 years, BMI 31 kg/m 2 , HOMA‐IR of 3.5 and HbA1c of 6.5%), testosterone gel treatment, despite expected changes in body composition (increase in lean mass by 1.9 kg and decrease in fat mass by 1.3 kg), had no effect on insulin sensitivity assessed by clamp, nor on HOMA‐IR or on HbA1c (Magnussen et al ., 2016). A subsequent magnetic resonance analysis of this cohort demonstrated no effect of testosterone treatment on metabolically adverse hepatic or visceral fat, but testosterone decreased the potentially insulin‐sensitizing adipokine adiponectin (Magnussen et al ., 2017). In contrast, a 24‐week clamp study enrolling 44 hypogonadal men (defined as free testosterone <225 pmol/L with a mean age 55 years, BMI 40 kg/m 2 , HOMA‐IR of 3.9, and HbA1c of 7.0%) while similarly demonstrating no change in visceral hepatic fat, found a 32% increase in insulin sensitivity with intramuscular testosterone treatment ( p = 0.03 for comparison with placebo), in association with upregulation of insulin signaling genes in adipose tissue (Dhindsa et al ., 2016).…”

Section: Metabolic Impact Of Testosterone Treatment In Clinical Trialsmentioning

confidence: 99%

Late‐onset hypogonadism: metabolic impact

2019

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Background Obesity and dysglycemia (comprising insulin resistance, the metabolic syndrome and type 2 diabetes), that is diabesity, are associated with reduced circulating testosterone and, in some men, clinical features consistent with androgen deficiency. Objective To review the metabolic impact of late‐onset hypogonadism. Methods Comprehensive literature search with emphasis on recent publications. Results Obesity is one of the strongest modifiable risk factors for late‐onset hypogonadism, and coexisting diabetes leads to further hypothalamic‐pituitary‐testicular axis suppression. The hypothalamic‐pituitary‐testicular axis suppression is functional and hence potentially reversible, and occurs predominantly at the level of the hypothalamus. While definitive mechanistic data are lacking, the evidence suggests that hypothalamic‐pituitary‐testicular axis suppression is mediated by dysregulation of pro‐inflammatory cytokines leading to hypothalamic inflammation. Dysregulation of central leptin and insulin signaling may also contribute. In contrast, recent data challenge the paradigm that estradiol excess is a major contributor to hypothalamic‐pituitary‐testicular axis suppression. Instead, relative estradiol signaling deficiency may contribute to metabolic dysregulation in men with diabesity. While weight loss and optimization of comorbidities can reverse functional hypothalamic‐pituitary‐testicular axis suppression, testosterone treatment leads to metabolically favorable changes in body composition and to improvements in insulin resistance. Discussion The relationship between diabesity and late‐onset hypogonadism is bidirectional. Preliminary evidence suggests that, in carefully selected men, lifestyle measures and testosterone treatment may have additive effects. Conclusions While recent research has provided new insights into mechanistic and clinical aspects of diabesity‐associated late‐onset hypogonadism, more evidence from well‐designed large trials is needed to guide the optimal clinical approach to such men.

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MR spectroscopy of hepatic fat and adiponectin and leptin levels during testosterone therapy in type 2 diabetes: a randomized, double-blinded, placebo-controlled trial

Cited by 26 publications

References 58 publications

Sex differences in body fat distribution are related to sex differences in serum leptin and adiponectin

Sex differences in body fat distribution are related to sex differences in serum leptin and adiponectin

Male Obesity-related Secondary Hypogonadism – Pathophysiology, Clinical Implications and Management

Late‐onset hypogonadism: metabolic impact

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