Total and Carboxylated Osteocalcin Associate with Insulin Levels in Young Adults Born with Normal or Very Low Birth Weight

Päivi M Paldánius,Kalervo Väänänen,Petteri Hovi,Outi Mäkitie,Eero Kajantie,Kaisa K Ivaska,Sture Andersson,Johan G Eriksson,Bridget Wagner

doi:10.1371/journal.pone.0063036

Abstract

ObjectiveOsteocalcin (OC), a bone-derived protein, has been implicated in the regulation of glucose and energy metabolism. Young adults born with very low birth weight (VLBW) have altered glucose regulation and lower bone mineral density (BMD) compared with those born at term. The aim of this study was to explore the association between bone and glucose metabolism in healthy young adults born prematurely or at term.MethodsThe cohort of this cross-sectional study comprised 332 non-diabetic young adults (age 18 to 27 years) born either preterm with VLBW (n = 163) or at term (n = 169). OC, carboxylated osteocalcin (cOC) and markers of glucose metabolism were measured at fasting and after a 75-g oral glucose tolerance test (OGTT).ResultsVLBW adults were shorter, had lower BMD (p<0.001) and higher fasting OC (p = 0.027) and cOC (p = 0.005) than term-born subjects. They also had higher 2-hour insulin (p = 0.001) and glucose (p = 0.037) concentrations. OGTT induced a significant reduction in OC (p<0.001), similar in both groups. OC reduction was not associated with OGTT-induced increases in insulin (p = 0.54). However, fasting total OC and cOC correlated negatively with fasting insulin after adjustment for age, gender, BMD and VLBW status (r = −0.182, p = 0.009 and r = −0.283, p<0.001, respectively).ConclusionAdults born with VLBW have higher OC and cOC than their peers born at term. This may in part reflect the mechanisms that underlie their lower BMD and decreased insulin sensitivity. Serum OC appears to be negatively associated with long-term glucose regulation whereas acute changes during OGTT may be mediated via other mechanisms.

Highlights

Glucose homeostasis depends on a complex signal network orchestrated by the pancreatic islet cells, liver, fat, muscle, kidney and brain
Young adults born preterm with very low birth weight (VLBW), while mostly normoglycemic, have lower insulin sensitivity when compared with those born at term [18,19]
The aim of this study was to explore the association between bone and glucose metabolism by evaluating OC, carboxylated osteocalcin and markers of glucose and insulin metabolism before and during a standard oral glucose tolerance test in apparently healthy young adults born either prematurely with VLBW or at term

Summary

Introduction

Glucose homeostasis depends on a complex signal network orchestrated by the pancreatic islet cells, liver, fat, muscle, kidney and brain. Preliminary data indicate that the cross-talk between bone and glucose-insulin metabolism could in part be mediated by OC [7]. Presence of such regulatory pathways in humans has not yet been confirmed [8], even if the body of knowledge is constantly increasing [9]. An inverse association between OC and markers of metabolic dysfunction has been reported in clinical studies evaluating markers of impaired glucose regulation [10,11,12,13,14]. While some of the reported associations are relatively strong, no direct causal relationship between changes in glucose regulation, insulin sensitivity and changes in OC has been confirmed in humans.

Methods

Results

Conclusion