Testosterone and type 2 diabetes prevention: translational lessons from the T4DM study

Area of Science:

• Endocrinology
• Metabolic Health
• Gerontology

Background:

• Testosterone plays a crucial role in adipose tissue, bone, and skeletal muscle.
• Lower testosterone levels are linked to obesity, disordered glucose metabolism, and increased type 2 diabetes (T2D) risk in men.
• Testosterone influences erythrocytosis and vascular function, impacting cardiovascular health.

Purpose of the Study:

• To evaluate the efficacy of testosterone undecanoate in preventing T2D in at-risk older men.
• To assess the impact of testosterone therapy on glycaemia, body composition, and cardiovascular risk factors.

Main Methods:

• The Testosterone for the Prevention of Type 2 Diabetes (T4DM) study enrolled men aged 50+ with specific metabolic criteria and low serum testosterone.
• Participants received 1000 mg of testosterone undecanoate intramuscularly every 3 months for 2 years, alongside a lifestyle program, compared to placebo.
• Measurements included T2D diagnosis, fasting serum glucose, HbA1c, body composition, strength, bone density, and cardiovascular events.

Main Results:

• Testosterone treatment reduced the likelihood of T2D diagnosis by 40% compared to placebo.
• Significant improvements were observed in fasting serum glucose, body composition, hand grip strength, bone mineral density, and skeletal microarchitecture.
• No increase in cardiovascular adverse events was reported, but HbA1c did not improve.

Conclusions:

• Testosterone undecanoate therapy, combined with lifestyle changes, is effective in preventing T2D in at-risk older men.
• The benefits extend to improved glycaemia, body composition, and musculoskeletal health.
• Further research is needed to understand the long-term effects on the hypothalamo-pituitary-testicular axis and cardiovascular outcomes.