title: Serum osteocalcin is not associated with glucose but is inversely associated with leptin across generations of nondiabetic women.
abstract: BACKGROUND
  The skeleton is recognized as an important player in energy metabolism through its interactions with other tissues. Whether the association of osteocalcin with glucose metabolism is age dependent has not been fully addressed.
  
  
  OBJECTIVE
  The objective of the study was to examine the age-specific association between different forms of osteocalcin and glucose and adipokines.
  
  
  METHODS
  This was a family-based study across three generations.
  
  
  METHODS
  The study was conducted at a university laboratory.
  
  
  METHODS
  Sixty-four daughter-premenopausal mother-maternal grandmother trios participated in the study.
  
  
  METHODS
  Fasting plasma glucose and insulin concentrations, serum total (tOC), carboxylated (cOC), and uncarboxylated (ucOC = tOC - cOC) osteocalcin, leptin, and adiponectin levels, and fat masses were assessed. Generalized estimating equations (GEE) model was used to assess the associations of bone biomarkers with glucose metabolism variables and adipokines.
  
  
  RESULTS
  No significant difference in insulin was found between generations, whereas glucose and leptin increased with age. Levels of tOC, cOC, and ucOC were highest in girls and lowest in mothers (P < 0.01). Grandmothers had higher leptin and adiponectin than mothers and girls. Despite the differences in insulin and glucose between the low and high homeostasis model assessment insulin resistance index (HOMA-IR) groups within generations, no significant differences in tOC, cOC, and ucOC were found. Compared with their low HOMA-IR counterparts, the high HOMA-IR group had significantly higher leptin and lower adiponectin in mothers and grandmothers. The tOC, cOC, and ucOC levels did not correlate with HOMA-IR, leptin, or adiponectin when the three generations were evaluated together, but when separated by generation, leptin was inversely correlated with tOC (P = 0.003) and cOC (P = 0.047) in mothers and with ucOC in grandmothers (P = 0.042).
  
  
  CONCLUSIONS
  Osteocalcin, glucose, and adipokines change with age but in a noncommensurate manner. We infer that the association between osteocalcin and glucose metabolism is minor and age specific in nondiabetic women. Leptin, however, strongly correlated with insulin resistance independently of fat masses, suggesting that obesity, as a metabolic disorder risk factor, affects glucose metabolism, partly through the role of leptin.
authors.affiliation: Department of Health Sciences, University of Jyväskylä, FIN-40014 Jyväskylä, Finland.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Lu
authors.forename: Kaisa K
authors.initials: KK
authors.lastname: Ivaska
authors.forename: Markku
authors.initials: M
authors.lastname: Alen
authors.forename: Qingju
authors.initials: Q
authors.lastname: Wang
authors.forename: Timo
authors.initials: T
authors.lastname: Törmäkangas
authors.forename: Leiting
authors.initials: L
authors.lastname: Xu
authors.forename: Petri
authors.initials: P
authors.lastname: Wiklund
authors.forename: Tuija M
authors.initials: TM
authors.lastname: Mikkola
authors.forename: Satu
authors.initials: S
authors.lastname: Pekkala
authors.forename: Haoming
authors.initials: H
authors.lastname: Tian
authors.forename: H Kalervo
authors.initials: HK
authors.lastname: Väänänen
authors.forename: Sulin
authors.initials: S
authors.lastname: Cheng
mesh_terms: D052242:Adiponectin / Q000097:blood; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood*; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood*; D017697:Premenopause
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D015675:Osteocalcin