Associations of Total and Undercarboxylated Osteocalcin with Peripheral and Hepatic Insulin Sensitivity and β-Cell Function in Overweight Adults

Barbara A. Gower, Norman K. Pollock, Krista Casazza, Thomas L. Clemens, Laura Lee Goree, Wesley M. Granger

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
JournalJournal of Clinical Endocrinology and Metabolism
Volume98
Issue number7
DOIs
StatePublished - Jul 1 2013

Fingerprint

Osteocalcin
Insulin Resistance
Insulin
Glucose
Liver
Meals
Glucose Tolerance Test
Adipose Tissue
Homeostasis
C-Peptide
Tissue
Collagen Type I
Research
Osteogenesis
Linear Models
Fasting
Protein Isoforms
Skeletal Muscle
Linear regression
Cross-Sectional Studies

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Associations of Total and Undercarboxylated Osteocalcin with Peripheral and Hepatic Insulin Sensitivity and β-Cell Function in Overweight Adults. / Gower, Barbara A.; Pollock, Norman K.; Casazza, Krista; Clemens, Thomas L.; Goree, Laura Lee; Granger, Wesley M.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 7, 01.07.2013.

Research output: Contribution to journalArticle

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title = "Associations of Total and Undercarboxylated Osteocalcin with Peripheral and Hepatic Insulin Sensitivity and β-Cell Function in Overweight Adults",
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.",
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T1 - Associations of Total and Undercarboxylated Osteocalcin with Peripheral and Hepatic Insulin Sensitivity and β-Cell Function in Overweight Adults

AU - Gower, Barbara A.

AU - Pollock, Norman K.

AU - Casazza, Krista

AU - Clemens, Thomas L.

AU - Goree, Laura Lee

AU - Granger, Wesley M.

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N2 - 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.

AB - 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.

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