The potential role of the osteopontin-osteocalcin-osteoprotegerin triad in the pathogenesis of prediabetes in humans

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.