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Determinants of undercarboxylated and carboxylated osteocalcin concentrations in type 1 diabetes

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Abstract

Summary

To determine whether undercarboxylated osteocalcin (UC-OC) or gamma-carboxyglutamic-carboxylated-type osteocalcin (GLA-OC) concentrations deviate from normal in type 1 diabetes (T1D), serum levels were compared between 115 subjects with T1D and 55 age-matched healthy controls. UC-OC and GLA-OC concentrations were similar between groups; however, in T1D, UC-OC correlated positively with markers of insulin exposure, either endogenously produced or exogenously administered.

Introduction

A study was conducted to determine whether dysregulation of circulating concentrations of UC-OC or GLA-OC occurs in patients with type 1 diabetes, a condition of insulin deficiency without insulin resistance.

Methods

We measured serum concentrations of UC-OC and GLA-OC in 115 subjects with T1D, ages 14–40 years, and in 55 age-matched healthy control subjects. Relationships between UC-OC and GLA-OC concentrations and patient characteristics (gender and age), indices of glycemic control (hemoglobin A1c (HbA1c), fasting plasma glucose, C-peptide concentration, 3-day average glucose measured by a continuous glucose sensor, total daily insulin dose) and circulating indices of skeletal homeostasis (total calcium, 25-OH vitamin D, parathyroid hormone, insulin-like growth factor 1 (IGF-1), type 1 collagen degradation fragments (CTX), adiponectin, leptin) were examined. Between group differences in the concentrations of UC-OC and GLA-OC were the main outcome measures.

Results

Although adiponectin levels were higher in the T1D group, between-group comparisons did not reveal statistically significant differences in concentration of UC-OC, GLA-OC, CTX or leptin between the T1D and control populations. Instead, by multivariate regression modeling, UC-OC was correlated with younger age (p < 0.001), higher CTX (p < 0.001), lower HbA1c (p = 0.013), and higher IGF-1 (p = 0.086). Moreover, within the T1D subgroup, UC-OC was positively correlated with C-peptide/glucose ratio (reflecting endogenous insulin secretion), with IGF-1 (reflecting intra-portal insulin sufficiency), and with total daily insulin dose.

Conclusions

In T1D, UC-OC appears to correlate positively with markers of insulin exposure, either endogenously produced or exogenously administered.

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Acknowledgements

This work was supported by grants from the National Institutes of Health to KMT (R01-DK62999); to the UAMS General Clinical Research Center (M01 RR14288) and to the Arkansas Children’s Hospital Research Institute (C06RR16517). Additional funding was provided by the Minnie Merrill Sturgis Diabetes Research Fund and the Arkansas Biosciences Institute. The authors are also grateful to the study subjects and their families for participation in this research.

Conflicts of interest

None.

Funding sources

Grants from the National Institutes of Health to KMT (R01-DK62999), to the UAMS General Clinical Research Center (M01 RR14288) and to the Arkansas Children’s Hospital Research Institute (C06RR16517), as well as funds from the Minnie Merrill Sturgis Diabetes Research Fund and the Arkansas Biosciences Institute.

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Author notes

  1. C.-H. Jo

    Present address: Research and Education Division, Scott and White Memorial Hospital, Temple, TX, 76508, USA

Authors and Affiliations

  1. Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital Research Institute, Little Rock, AR, 72205, USA

    K. M. Thrailkill, C.-H. Jo, G. E. Cockrell, C. S. Moreau, C. K. Lumpkin Jr & J. L. Fowlkes

  2. Arkansas Children’s Hospital, 1 Children’s Way, Slot 512-6, Little Rock, AR, 72202, USA

    K. M. Thrailkill

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  1. K. M. Thrailkill
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  6. J. L. Fowlkes
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Correspondence to K. M. Thrailkill.

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Thrailkill, K.M., Jo, CH., Cockrell, G.E. et al. Determinants of undercarboxylated and carboxylated osteocalcin concentrations in type 1 diabetes. Osteoporos Int 23, 1799–1806 (2012). https://doi.org/10.1007/s00198-011-1807-7

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