Undercarboxylated osteocalcin is positively associated with free testosterone in male patients with type 2 diabetes mellitus

Although a recent study showed that undercarboxylated osteocalcin (ucOC) is important for male fertility and testosterone production by testes, little is known about the relationship between ucOC and testosterone in humans. We found for the first time that ucOC is positively associated with free testosterone in men with type 2 diabetes. The ucOC has been shown to play a key role in energy metabolism as an endocrine hormone. Although a recent animal study demonstrated that ucOC is also important for male fertility and testosterone production by the testes, association between serum osteocalcin and testosterone levels has not been understood in humans. Sixty-nine male patients with type 2 diabetes were recruited and chemical bone markers [total osteocalcin (TOC), ucOC, bone-specific alkaline phosphatase (BAP), and urinary N-terminal cross-linked telopeptide of type I collagen (uNTX)], gonadotropic hormones [luteinizing hormone (LH) and follicle-stimulating hormone (FSH)], and free testosterone (FT) were measured. Multiple regression analysis showed that ucOC and ucOC/TOC ratio were associated positively with FT and negatively with LH (for ucOC, beta = 0.30, p = 0.042 and beta = -0.52, p = 0.048; for ucOC/TOC ratio, beta = 0.31, p = 0.031 and beta = -0.54, p = 0.036, respectively) independently of age, duration of diabetes, body mass index, and hemoglobin A1c. ucOC and ucOC/TOC ratio were significantly associated with FT even after adjusting for LH and FSH (beta = 0.24, p = 0.042 and beta = 0.25, p = 0.031, respectively). However, neither TOC, BAP, nor uNTX was associated with the gonadotropic hormones or FT levels. The present study indicates for the first time that ucOC is associated positively with FT and negatively with LH in type 2 diabetes. These findings support the recent evidence that ucOC is involved in testosterone production in male subjects.