Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025060
Type 2 diabetes mellitus (T2DM) is an endocrine metabolic disorder characterized by insulin secretion dysfunction and/or insulin resistance. Osteocalcin (OC), or bone γ-carboxyglutamic acid protein (BGP), is a bone matrix protein predominantly produced by osteoblasts. Vitamin K-dependent carboxylation converts OC into gamma-carboxyglutamic acid (Gla)-rich carboxylated osteocalcin (cOC), which binds to hydroxyapatite and can be decarboxylated to undercarboxylated osteocalcin (ucOC) under acidic conditions. While cOC influences bone formation and mineralization, ucOC regulates energy metabolism. This study aimed to explore the associations between T2DM, serum OC levels (including cOC and ucOC), and OC gene polymorphisms in the Chinese Han population. T2DM patients and a healthy cohort, all of Han ethnicity, were categorized into a T2DM group (n = 456) and a control group (n = 224). Serum levels of cOC and ucOC were determined via ELISA. Insulin sensitivity was assessed via HOMA-IR, and pancreatic β-cell function via HOMA-β. Nine SNPs in the OC gene were genotyped via SNaPshot. Compared with controls, T2DM patients presented significantly lower levels of ucOC, cOC, and ucOC/cOC ratio. Additionally, T2DM subjects had elevated BMI, HbA1c, HOMA-IR, ALP, TG, HDL, and LDL levels, with decreased HOMA-β, ALT, AST, hsCRP, and FFA levels. In terms of bone metabolism, T2DM patients presented increased blood phosphorus, ICTP, P1NP, and 25(OH)D levels and decreased blood calcium, N-MID, PTH, and β-CTX levels. Associations between serum cOC and ucOC and various factors were analyzed. In the T2DM group, cOC was inversely correlated with HbA1c and P1NP, and positively correlated with ALP, LDL, and N-MID. ucOC was positively associated with N-MID. In controls, cOC was positively correlated with HDL, N-MID, and PINP, while ucOC correlated with PINP. The study also examined SNPs in the OC gene and their relationships with serum cOC and ucOC.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025060
Type 2 diabetes mellitus (T2DM) is an endocrine metabolic disorder characterized by insulin secretion dysfunction and/or insulin resistance. Osteocalcin (OC), or bone γ-carboxyglutamic acid protein (BGP), is a bone matrix protein predominantly produced by osteoblasts. Vitamin K-dependent carboxylation converts OC into gamma-carboxyglutamic acid (Gla)-rich carboxylated osteocalcin (cOC), which binds to hydroxyapatite and can be decarboxylated to undercarboxylated osteocalcin (ucOC) under acidic conditions. While cOC influences bone formation and mineralization, ucOC regulates energy metabolism. OC enhances adiponectin production and insulin sensitivity; however, its relationship with diabetes incidence and glucose levels remains controversial. This study aimed to explore the associations between T2DM, serum OC levels (including cOC and ucOC), and OC gene polymorphisms in the Chinese Han population. T2DM patients and a healthy cohort, all of Han ethnicity, were categorized into a T2DM group (n = 456) and a control group (n = 224). Serum levels of cOC and ucOC were determined via enzyme-linked immunosorbent assay. Insulin sensitivity was assessed via homeostatic model assessment of insulin resistance (HOMA-IR). Pancreatic β-cell function was evaluated with HOMA-β. Nine SNPs in the OC gene were selected from the International HapMap Project database: rs12563631, rs2241106, rs2277872, rs2758605, rs1543294, rs1800247, rs2842880, rs759330, and rs933489. Genotyping was conducted via the SNaPshot technique. Pearson correlation and multiple linear regression analyses were performed. Compared with controls, T2DM patients presented significantly lower levels of ucOC (0.82 ng/mL), cOC (12.19 ng/mL), and ucOC/cOC ratio (0.07) (1.17 ng/mL, 14.47 ng/mL, and 0.09, respectively). Additionally, T2DM subjects had elevated BMI (25.06 kg/m2), HbA1c (8.95%), HOMA-IR (0.61), ALP (79.00 U/L), and TG (1.50 mM). Notably, cOC levels exhibit a significant inverse correlation with HbA1c, whereas no such correlation was observed for ucOC. The CC genotype at rs933489 is associated with lower ucOC levels in Chinese Han T2DM patients. These findings provide novel perspectives on the role of OC in T2DM pathophysiology.