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Purpose <p>Bone-derived cytokines have been implicated in glucose metabolism, but their role in type 1 diabetes mellitus (T1DM) is unclear. We investigated alterations in bone turnover markers (BTMs) and their associations with β-cell function and autoimmunity in T1DM.</p> Methods <p>This cross-sectional study enrolled 369 T1DM individuals and 150 matched controls. Serum BTMs, fasting C-peptide (FCP), HbA1c, glucose, and islet-autoimmune profile were measured. Analyses included group comparisons, linear regression, and Locally Estimated Scatterplot Smoothing (LOESS) to visualize the relationships of FCP and osteocalcin (OC) with disease duration. A logistic-regression model incorporating OC was developed to assess β-cell failure in participants at early stage of established T1DM.</p> Results <p>Serum BTMs were significantly lower in T1DM versus controls, and lowest in the low-FCP subgroup. Only log<sub>e</sub>-transformed OC (ln[OC]) remained independently associated with log<sub>e</sub>-transformed FCP (ln[FCP]) after adjustment (β = 0.38, <i>P</i> = 0.036). LOESS modelling revealed biphasic FCP decline (rapid within 2 years, then slow), while OC rose initially, peaking at 2 years before declining. The positive ln[OC]-ln[FCP] association was significant only within 5 years post-diagnosis. In this early stage, OC also correlated with regulatory T cells frequency (<i>r</i> = 0.319, <i>P</i> = 0.009). A model combining OC, body mass index, duration, insulin dose, age, and glucose discriminated severe β-cell failure with an AUC of 0.83 (95% confidence interval: 0.77–0.89).</p> Conclusion <p>In early-established T1DM, OC independently associates with preserved β-cell function. Higher OC levels were accompanied by better β-cell function and an expanded regulatory T-cell pool, suggesting a potential role in the islet immune microenvironment.</p>

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Higher osteocalcin levels are associated with preserved β-cell function in early-established type 1 diabetes

  • 期刊论文

  • 发表日期：

    2026年4月11日

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  • Tingting Zhuang,
  • Qixiang Yang,
  • Donghui Yang,
  • Lei Qian,
  • Yan Bi,
  • Jing Lu

摘要

Purpose

Bone-derived cytokines have been implicated in glucose metabolism, but their role in type 1 diabetes mellitus (T1DM) is unclear. We investigated alterations in bone turnover markers (BTMs) and their associations with β-cell function and autoimmunity in T1DM.

Methods

This cross-sectional study enrolled 369 T1DM individuals and 150 matched controls. Serum BTMs, fasting C-peptide (FCP), HbA1c, glucose, and islet-autoimmune profile were measured. Analyses included group comparisons, linear regression, and Locally Estimated Scatterplot Smoothing (LOESS) to visualize the relationships of FCP and osteocalcin (OC) with disease duration. A logistic-regression model incorporating OC was developed to assess β-cell failure in participants at early stage of established T1DM.

Results

Serum BTMs were significantly lower in T1DM versus controls, and lowest in the low-FCP subgroup. Only loge-transformed OC (ln[OC]) remained independently associated with loge-transformed FCP (ln[FCP]) after adjustment (β = 0.38, P = 0.036). LOESS modelling revealed biphasic FCP decline (rapid within 2 years, then slow), while OC rose initially, peaking at 2 years before declining. The positive ln[OC]-ln[FCP] association was significant only within 5 years post-diagnosis. In this early stage, OC also correlated with regulatory T cells frequency (r = 0.319, P = 0.009). A model combining OC, body mass index, duration, insulin dose, age, and glucose discriminated severe β-cell failure with an AUC of 0.83 (95% confidence interval: 0.77–0.89).

Conclusion

In early-established T1DM, OC independently associates with preserved β-cell function. Higher OC levels were accompanied by better β-cell function and an expanded regulatory T-cell pool, suggesting a potential role in the islet immune microenvironment.