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

Area of Science:

• Endocrinology
• Metabolic Diseases
• Bone Biology

Background:

• Bone-derived cytokines influence glucose metabolism, but their role in type 1 diabetes mellitus (T1DM) remains unclear.
• Investigating bone turnover markers (BTMs) in T1DM is crucial for understanding disease pathophysiology and potential therapeutic targets.

Purpose of the Study:

• To investigate alterations in BTMs in T1DM patients compared to healthy controls.
• To examine the association between BTMs, specifically osteocalcin (OC), with beta-cell function (measured by fasting C-peptide, FCP) and autoimmunity in T1DM.
• To develop a predictive model for beta-cell failure in early T1DM using OC and other clinical parameters.

Main Methods:

• A cross-sectional study involving 369 T1DM individuals and 150 matched controls.
• Serum BTMs, FCP, HbA1c, glucose, and islet-autoimmune markers were measured.
• Statistical analyses included group comparisons, linear regression, and LOESS modeling to assess relationships between FCP, OC, and disease duration. A logistic-regression model was developed to predict beta-cell failure.

Main Results:

• T1DM patients exhibited significantly lower serum BTMs compared to controls, with the lowest levels in the low-FCP subgroup.
• Log-transformed osteocalcin (ln[OC]) was independently associated with log-transformed fasting C-peptide (ln[FCP]) (β = 0.38, P = 0.036).
• LOESS modeling showed a biphasic FCP decline and an initial rise in OC, peaking at 2 years post-diagnosis. The positive ln[OC]-ln[FCP] association was significant within 5 years post-diagnosis. Higher OC levels correlated with regulatory T cell frequency (r = 0.319, P = 0.009).
• A predictive model incorporating OC, BMI, duration, insulin dose, age, and glucose achieved an AUC of 0.83 for discriminating severe beta-cell failure.

Conclusions:

• Osteocalcin (OC) independently associates with preserved beta-cell function in early-established T1DM.
• Higher OC levels correlate with better beta-cell function and an increased regulatory T-cell pool.
• These findings suggest a potential role for OC in modulating the islet immune microenvironment in T1DM.