TY - JOUR
T1 - The potential role of the osteopontin–osteocalcin–osteoprotegerin triad in the pathogenesis of prediabetes in humans
AU - Daniele, Giuseppe
AU - Winnier, Deidre A
AU - Mari, Andrea
AU - Bruder, Jan
AU - Fourcaudot, Marcel
AU - Pengou, Zuo
AU - Hansis-Diarte, Andrea
AU - Jenkinson, Christopher P
AU - Tripathy, Devjit
AU - Folli, Franco
N1 - Publisher Copyright:
© 2017, The Author(s).
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Aims: To examine the relationship between hormones involved in bone remodeling and glucose metabolism alterations in prediabetes. Methods: Individuals (n = 43) with NGT (BMI = 31.1 ± 1.1 kg/m2) and individuals (n = 79) with impaired glucose regulation (IGR) (BMI = 31.9 ± 1.2 kg/m2) including subjects with IFG, IGT, and IFG-IGT underwent OGTT and DXA. Osteopontin (OPN), osteocalcin (OCN), osteoprotegerin (OPG), and PTH levels were measured at fasting. Beta-cell function was calculated using C-peptide deconvolution. Dynamic indexes of insulin sensitivity were calculated from OGTT. A subgroup underwent to a euglycemic hyperinsulinemic clamp with 3-3H-glucose to estimate the endogenous glucose production (EGP) and insulin-mediated body glucose disposal (TGD/SSPI). Results: OPN was higher in IGR compared to NGT (5.3 ± 0.5 vs. 3.3 ± 0.2 μg/mL; p = 0.008) and in isolated IGT compared to IFG and IFG-IGT (6.3 ± 0.5 vs. 4.5 ± 0.3 and 5.4 ± 0.5 μg/mL; p = 0.02). OCN was similar in IFG and NGT but lower in IGT and IFG-IGT compared to NGT (7.2 ± 0.3 and 5.4 ± 0.2 vs. 8.3 ± 0.3 ng/mL; p < 0.01). OPN was positively correlated with HbA1c, fasting and 2 h plasma glucose and PTH. OCN was negatively correlated with body fat, 2 h plasma glucose, insulin and positively correlated with Stumvoll index. OPG correlated with TGD/SSPI (r = − 0.29; p < 0.05), EGP, and hepatic insulin resistance index in IGR (r = 0.51, r = 0.43; p < 0.01). There was no correlation between PTH and insulin sensitivity or Beta-cell function parameters. Conclusions: In prediabetes, hormones known to be involved in bone remodeling may affect glucose metabolism before overt T2DM occurs with tissue-specific mechanisms.
AB - Aims: To examine the relationship between hormones involved in bone remodeling and glucose metabolism alterations in prediabetes. Methods: Individuals (n = 43) with NGT (BMI = 31.1 ± 1.1 kg/m2) and individuals (n = 79) with impaired glucose regulation (IGR) (BMI = 31.9 ± 1.2 kg/m2) including subjects with IFG, IGT, and IFG-IGT underwent OGTT and DXA. Osteopontin (OPN), osteocalcin (OCN), osteoprotegerin (OPG), and PTH levels were measured at fasting. Beta-cell function was calculated using C-peptide deconvolution. Dynamic indexes of insulin sensitivity were calculated from OGTT. A subgroup underwent to a euglycemic hyperinsulinemic clamp with 3-3H-glucose to estimate the endogenous glucose production (EGP) and insulin-mediated body glucose disposal (TGD/SSPI). Results: OPN was higher in IGR compared to NGT (5.3 ± 0.5 vs. 3.3 ± 0.2 μg/mL; p = 0.008) and in isolated IGT compared to IFG and IFG-IGT (6.3 ± 0.5 vs. 4.5 ± 0.3 and 5.4 ± 0.5 μg/mL; p = 0.02). OCN was similar in IFG and NGT but lower in IGT and IFG-IGT compared to NGT (7.2 ± 0.3 and 5.4 ± 0.2 vs. 8.3 ± 0.3 ng/mL; p < 0.01). OPN was positively correlated with HbA1c, fasting and 2 h plasma glucose and PTH. OCN was negatively correlated with body fat, 2 h plasma glucose, insulin and positively correlated with Stumvoll index. OPG correlated with TGD/SSPI (r = − 0.29; p < 0.05), EGP, and hepatic insulin resistance index in IGR (r = 0.51, r = 0.43; p < 0.01). There was no correlation between PTH and insulin sensitivity or Beta-cell function parameters. Conclusions: In prediabetes, hormones known to be involved in bone remodeling may affect glucose metabolism before overt T2DM occurs with tissue-specific mechanisms.
KW - Adiponectin
KW - Beta-cell function
KW - Euglycemic hyperinsulinemic clamp
KW - Glucose metabolism
KW - Human
KW - Impaired fasting glucose
KW - Impaired glucose regulation
KW - Impaired glucose tolerance
KW - Leptin
KW - Osteocalcin
KW - Osteopontin
KW - Osteoprotegerin
KW - Prediabetes
KW - Type 2 diabetes mellitus
KW - Whole body insulin sensitivity
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U2 - 10.1007/s00592-017-1065-z
DO - 10.1007/s00592-017-1065-z
M3 - Article
C2 - 29151224
AN - SCOPUS:85034222863
SN - 0940-5429
VL - 55
SP - 139
EP - 148
JO - Acta Diabetologica
JF - Acta Diabetologica
IS - 2
ER -