Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy

Magnussen, Line Velling; Glintborg, Dorte; Hermann, Pernille; Hougaard, David M.; Højlund, Kurt; Andersen, Marianne

doi:10.1111/dom.12701

Cited by 55 publications

(85 citation statements)

References 45 publications

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“…As previously reported, TLBM increased ( b = 1.9 kg) whereas TFM decreased ( b = −1.3 kg) during testosterone therapy compared with placebo (Magnussen et al ., ). Lean leg mass also increased ( b = 0.48 kg) compared with placebo (Table and Fig.…”

Section: Resultsmentioning

confidence: 97%

“…Adverse events and serious adverse events were recorded throughout the study (Magnussen et al ., ). Three patients discontinued in the study due to unrelated illnesses or personal reasons, while one patient in the testosterone group was reduced to 5 g gel once every other day due to elevated hematocrit level.…”

Section: Resultsmentioning

confidence: 97%

“…As previously reported (Magnussen et al ., ), increases ( p < 0.05) were observed in TotalT ( b = 14.5 nmol/L), BioT ( b = 7.6 nmol/L), and FreeT ( b = 0.32 nmol/L) during testosterone replacement therapy (TRT) compared with placebo, along with a decrease ( p < 0.05) in SHBG ( n = −2 nmol/L) (Table ).…”

Section: Resultsmentioning

confidence: 99%

“…The design of the trial has been reported in detail elsewhere (Magnussen et al ., ). Briefly, Caucasian men aged 50–70 years, BioT levels <7.3 nmol/L (Nielsen et al ., ), a diagnosis of T2D and stable treatment with metformin (only anti‐diabetic drug permitted) at least three months prior to inclusion were eligible for inclusion.…”

Section: Methodsmentioning

confidence: 97%

“…Patients were told to stop gel therapy 24 h before blood sampling at week 3 and the second day of the final visit. The sample size of the original study (Magnussen et al ., ) was determined by the anticipated effect of TRT on TLBM (Isidori et al ., ), resulting in 20 patients in each group. In the present explorative study, the primary outcome was isometric muscle strength (MVC), and the secondary outcomes included additional measures of muscle mechanical function (explosive strength, dynamic strength, and power), physical function (gait speed), lean leg mass, TLBM, TFM, and leg fat mass.…”

Section: Methodsmentioning

confidence: 99%

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Testosterone therapy preserves muscle strength and power in aging men with type 2 diabetes—a randomized controlled trial

et al. 2017

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The purpose of the study was to evaluate whether testosterone replacement therapy improves muscle mechanical and physical function in addition to increasing lean leg mass and total lean body mass in aging men with type 2 diabetes and lowered bio-available testosterone (BioT) levels. Thirty-nine men aged 50-70 years with type 2 diabetes and BioT levels <7.3 nmol/L were included from an academic tertiary-care medical center. Patients were randomized to testosterone gel (testosterone replacement therapy, n = 20) or placebo (n = 19) for 24 weeks, applying a double-blinded design. Muscle mechanical function was assessed by Nottingham Leg Rig (leg extension power) and isokinetic dynamometry (knee extensor maximal isometric contraction, rate of force development (RFD100), maximal dynamic contraction (Dyn180)). Physical function was assessed by gait speed. Body composition was assessed by whole body dual-energy X-ray absorptiometry (total lean body mass, lean leg mass, total fat mass, leg fat mass). Levels of total testosterone (TotalT), BioT, free testosterone (FreeT), and sex hormone-binding globulin were measured from fasting blood samples. Coefficients (b) represent the placebo-controlled mean effect of intervention. Maximal isometric contraction (b = 18.4 Nm, p = 0.039), RFD100 (b = 195.0 Nm/s, p = 0.017) and Dyn180 (b = 10.2 Nm, p = 0.019) increased during testosterone replacement therapy compared with placebo. No changes were observed in leg power or gait speed. Total lean body mass (b = 1.9 kg, p = 0.001) and lean leg mass (b = 0.5 kg, p < 0.001) increased, while total fat mass (b = -1.3 kg, p = 0.009) and leg fat mass (b = -0.7 kg, p = 0.025) decreased during testosterone replacement therapy compared with placebo. Total T (b = 14.5 nmol/L, p = 0.056), BioT (b = 7.6 nmol/L, p = 0.046), and FreeT (b = 0.32 nmol/L, p = 0.046) increased during testosterone replacement therapy compared with placebo, while sex hormone-binding globulin (n = -2 nmol/L, p = 0.030) decreased. Knee extensor muscle mechanical function was preserved, and body composition improved substantially during testosterone replacement therapy for 24 weeks compared with placebo, whereas physical function (gait speed) was unchanged in aging men with type 2 diabetes and lowered BioT levels.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

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Testosterone therapy preserves muscle strength and power in aging men with type 2 diabetes—a randomized controlled trial

et al. 2017

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Testicular function

Dhindsa

2022

Pathy's Principles and Practice of Geriatric Medicine

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Androgens and the Regulation of Adiposity and Body Fat Distribution in Humans

Tchernof

Brochu

Maltais‐Payette

et al. 2018

Comprehensive Physiology

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The sexual dimorphism in human body fat distribution suggests a causal role for sex hormones. This is of particular importance when considering the role of excess visceral adipose tissue accumulation as a critical determinant of obesity-related cardiometabolic alterations. Scientific literature on the modulation of body fat distribution by androgens in humans is abundant, remarkably inconsistent and difficult to summarize. We reviewed relevant literature on this topic, with a particular emphasis on androgen replacement, androgen effects on selected parameters of adipose tissue function and adipose tissue steroid-converting enzymes. In men, low androgenic status mostly reflected by reduced total testosterone is a frequent feature of visceral obesity and the metabolic syndrome. Regarding testosterone therapy, however, studies must be appreciated in the context of current controversies on their cardiovascular effects. Analyses of available studies suggest that decreases in waist circumference in response to testosterone are more likely observed in men with low levels of testosterone and high BMI at study onset. In women with androgen excess, higher testosterone and free testosterone levels are fairly consistent predictors of increased abdominal and/or visceral adipose tissue accumulation, which is not the case in nonhyperandrogenic women. Regarding mechanisms, androgens decrease adipogenesis and markers of lipid storage in vitro in men and women. Evidence also suggest that local steroid transformations by adipose tissue steroid-converting enzymes expressed in a depot-specific fashion may play a role in androgen-mediated modulation of body fat distribution. Accumulating evidence shows that androgens are critical modulators of body fat distribution in both men and women. © 2018 American Physiological Society. Compr Physiol 8:1253-1290, 2018.

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Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy

Abstract: TRT in aging men with lowered BioT levels and T2D controlled on metformin monotherapy improved body composition; however, glycaemic control, peripheral insulin sensitivity, EGP and substrate metabolism were unchanged.

Cited by 55 publications

References 45 publications

Testosterone therapy preserves muscle strength and power in aging men with type 2 diabetes—a randomized controlled trial

Testosterone therapy preserves muscle strength and power in aging men with type 2 diabetes—a randomized controlled trial

Testicular function

Androgens and the Regulation of Adiposity and Body Fat Distribution in Humans

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