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

Academic Article


  • 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.
  • Keywords

  • Adult, Biomarkers, Body Mass Index, C-Peptide, Cohort Studies, Cross-Sectional Studies, Female, Glucose Intolerance, Humans, Insulin, Insulin Resistance, Insulin Secretion, Insulin-Secreting Cells, Intra-Abdominal Fat, Liver, Male, Middle Aged, Models, Biological, Muscle, Skeletal, Osteocalcin, Overweight, Peptide Fragments, Procollagen, Protein Processing, Post-Translational, Young Adult
  • Digital Object Identifier (doi)

    Author List

  • Gower BA; Pollock NK; Casazza K; Clemens TL; Goree LL; Granger WM
  • Start Page

  • E1173
  • End Page

  • E1180
  • Volume

  • 98
  • Issue

  • 7