The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes

Objective: Serum testosterone levels are known to inversely correlate with insulin sensitivity and obesity in men. Furthermore, there is evidence to suggest that testosterone replacement therapy reduces insulin resistance and visceral adiposity in type 2 diabetic men. Adipocytokines are hormones secreted by adipose tissue and contribute to insulin resistance. We examined the effects of testosterone replacement treatment on various adipocytokines and C-reactive protein (CRP) in type 2 diabetic men. Design: Double-blinded placebo-controlled crossover study in 20 hypogonadal type 2 diabetic men. Patients were treated with testosterone (sustanon 200 mg) or placebo intramuscularly every 2 weeks for 3 months in random order followed by a washout period of 1 month before the alternate treatment phase. Methods: Leptin, adiponectin, resistin. tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and CRP levels were measured before and after each treatment phase. Body mass index (BMI) and waist circumference were also recorded. Results: At baseline. leptin levels significantly correlated with BMI and waist circumference. There was a significant inverse correlation between baseline IL-6 and total testosterone (r= -0.68: P=0.002) and bioavailable testosterone levels (r= -0.73: P=0.007). CRP levels also correlated significantly with total testosterone levels (r= -0.59; P=0.01). Testosterone treatment reduced leptin (- 7141.9 +/- 1461.8 pg/ml; P=0.0001) and adiponectin levels (-2075.8 +/- 852.3 ng/ml; P=0.02). There was a significant reduction in waist circumference. No significant effects of testosterone therapy on resistin, TNF-alpha, IL-6 or CRP levels were observed. Conclusion: Testosterone replacement treatment decreases leptin and adiponectin levels in type 2 diabetic men. Moreover, low levels of testosterone in men are associated with pro-inflammatory profile, though testosterone treatment over 3 months had no effect on inflammatory markers.