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Clinical Trial
. 2013 Jul;98(7):E1173-80.
doi: 10.1210/jc.2013-1203. Epub 2013 Apr 24.

Associations of total and undercarboxylated osteocalcin with peripheral and hepatic insulin sensitivity and β-cell function in overweight adults

Barbara A Gower  1 , Norman K Pollock, Krista Casazza, Thomas L Clemens, Laura Lee Goree, Wesley M Granger
Affiliations
Clinical Trial

Associations of total and undercarboxylated osteocalcin with peripheral and hepatic insulin sensitivity and β-cell function in overweight adults

Barbara A Gower et al. J Clin Endocrinol Metab. 2013 Jul.

Erratum in

  • Corrigenda.
    [No authors listed] [No authors listed] J Clin Endocrinol Metab. 2016 May;101(5):2265. doi: 10.1210/jc.2016-1578. J Clin Endocrinol Metab. 2016. PMID: 27163465 Free PMC article. No abstract available.

Abstract

Context: Animal studies indicate that osteocalcin (OC), particularly the undercarboxylated isoform (unOC), affects insulin sensitivity and secretion, but definitive data from humans are lacking.

Objective: The objectives of the study were to determine whether total OC and unOC are independently associated with insulin sensitivity and β-cell response in overweight/obese adults; whether glucose tolerance status affects these associations; and whether the associations are independent of bone formation, as reflected in procollagen type 1 amino propeptide (P1NP).

Design, setting, and participants: This was a cross-sectional study conducted at a university research center involving 63 overweight/obese adults with normal (n = 39) or impaired fasting glucose (IFG; n = 24).

Main outcome measures: Serum concentrations of total/undercarboxylated OC and P1NP were assessed by RIA; insulin sensitivity was determined by iv glucose tolerance test (S(I)-IVGTT), liquid meal test (S(I) meal), and homeostasis model assessment of insulin resistance; β-cell response to glucose [basal β-cell response to glucose; dynamic β-cell response to glucose; static β-cell response to glucose; and total β-cell response to glucose] was derived using C-peptide modeling of meal test data; and intraabdominal adipose tissue was measured using computed tomography scanning.

Results: Multiple linear regression, adjusting for intraabdominal adipose tissue and P1NP, revealed that total OC was positively associated with S(I)-iv glucose tolerance test (P < .01) in the total sample. OC was not associated with S(I) meal or homeostasis model assessment of insulin resistance. In participants with IFG, unOC was positively associated with static β-cell response to glucose and total β-cell response to glucose (P < .05), independent of insulin sensitivity.

Conclusions: In overweight/obese individuals, total OC may be associated with skeletal muscle but not hepatic insulin sensitivity. unOC is uniquely associated with β-cell function only in individuals with IFG. Further research is needed to probe the causal inference of these relationships and to determine whether indirect nutrient sensing pathways underlie these associations.

Trial registration: ClinicalTrials.gov NCT00726908.

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Figures

Figure 1.
Figure 1.
Unadjusted associations between P1NP and SI-meal in all participants combined (NGT and IFG) (r = −0.40, P < .01) (A) and unOC and PhiTOT in participants with IFG (r = 0.49, P < .05) (B).
Figure 2.
Figure 2.
Partial correlation between total OC and SI-IVGTT in all participants combined (NGT and IFG); data are adjusted for IAAT and P1NP (r = 0.28, P < .01).
See this image and copyright information in PMC

References

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    1. Pollock NK, Bernard PJ, Gower BA, et al. Lower uncarboxylated osteocalcin concentrations in children with prediabetes is associated with β-cell function. J Clin Endocrinol Metab. 2011;96:E1092–E1099 - PMC - PubMed

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