The Association Between Osteocalcin and Chronic Inflammation in Patients with Type 2 Diabetes Mellitus

Osteocalcin acts as an endocrine hormone to regulate energy homeostasis. Although several in vivo and in vitro studies suggest that osteocalcin is involved in chronic inflammation, the association between osteocalcin and chronic inflammation in humans is unknown. In this cross-sectional study, 246 patients with type 2 diabetes mellitus (T2DM) were recruited to investigate the association of bone turnover markers with chronic inflammation parameters such as high-sensitive C-reactive protein (hsCRP), ferritin, and leukocyte subtype counts. Bone-specific alkaline phosphatase (BAP), total osteocalcin (OC), undercarboxylated OC (ucOC), and urinary N-terminal cross-linked telopeptide of type-I collagen (uNTX) were measured. Multiple regression analysis adjusted for age, duration of diabetes, body mass index, estimated glomerular filtration rate, and hemoglobin A1c showed that serum OC levels were significantly and negatively associated with hsCRP, ferritin, basophil count, and monocyte count (=-0.18, p=0.013; =-0.22, p=0.031; =-0.14, p=0.038; and =-0.17, p=0.012, respectively). Moreover, serum ucOC levels were significantly and negatively associated with hsCRP, ferritin, total leukocyte count, neutrophil count, and monocyte count (=-0.24, p=0.007; =-0.37, p=0.003; =-0.21, p=0.007; =-0.24, p=0.002; and =-0.20, p=0.011, respectively). The ratio of ucOC to OC was significantly and negatively associated with ferritin (=-0.31, p=0.014). However, neither BAP nor uNTX was associated with any chronic inflammation parameters. This is the first study to show that serum OC and ucOC levels were negatively associated with chronic inflammation parameters such as hsCRP, ferritin, and leukocyte subtypes in patients with T2DM. Therefore, OC could be a therapeutic target for protecting against chronic inflammation.