Key Takeaways & Executive Findings
- •• T2DM patients had significantly lower serum levels of cOC, ucOC, and ucOC/cOC ratio compared to healthy controls, suggesting altered osteocalcin metabolism in diabetes. • In T2DM, cOC levels inversely correlated with HbA1c and P1NP, while positively correlated with ALP, LDL, and N-MID, indicating potential links between bone turnover and glycemic control. • Nine SNPs in the osteocalcin gene were analyzed, providing preliminary evidence for genetic associations with osteocalcin levels and T2DM risk in the Chinese Han population. • The study highlights the interplay between bone-derived hormones and metabolic health, offering potential biomarkers for T2DM diagnosis and management.
Abstract
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.
1. Introduction
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), which was initially identified in chicken bone in 1975 [1], is a bone matrix protein predominantly produced by osteoblasts [2,3]. 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 and has garnered research interest [4]. OC enhances adiponectin production and insulin sensitivity; however, its relationship with diabetes incidence and glucose levels remains controversial [5]. 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.
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Luyue Qi, Hong Wu, Xiangqi Li, Yang Xu, Liangyong Liu (2026). Osteocalcin carboxylation/undercarboxylation levels and gene variants associated with type 2 diabetes mellitus in the Chinese Han population. Acta Biochimica et Biophysica Sinica. https://doi.org/10.3724/abbs.2025060
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Frequently Asked Questions
What is the role of osteocalcin in type 2 diabetes mellitus?
Osteocalcin, particularly its undercarboxylated form (ucOC), is believed to regulate energy metabolism by enhancing insulin sensitivity and adiponectin production. This study found that T2DM patients had lower serum levels of cOC and ucOC, suggesting a potential link between osteocalcin and diabetes pathophysiology.
How were osteocalcin levels measured in this study?
Serum levels of carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC) were determined using an enzyme-linked immunosorbent assay (ELISA) kit from TaKaRa, Dalian, China.
What were the key findings regarding osteocalcin gene variants?
The study analyzed nine SNPs in the osteocalcin gene and their associations with serum cOC and ucOC levels. While specific results are not detailed in the abstract, the study suggests that genetic variants may influence osteocalcin levels and T2DM susceptibility in the Chinese Han population.
What is the significance of the ucOC/cOC ratio in T2DM?
The ucOC/cOC ratio was significantly lower in T2DM patients compared to controls, indicating a shift in osteocalcin carboxylation status. This ratio may serve as a biomarker for metabolic disturbances in T2DM.
How does this study contribute to the understanding of bone-diabetes interactions?
This study provides evidence that bone-derived osteocalcin is associated with glycemic control and bone turnover markers in T2DM, supporting the concept of bone as an endocrine organ involved in glucose metabolism.
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