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

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9200299 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-5233 (Electronic) Linking ISSN: 09405429 NLM ISO Abbreviation: Acta Diabetol Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin : Springer International, c1991-

Glucose Intolerance/*blood ; Osteocalcin/*blood ; Osteopontin/*blood ; Osteoprotegerin/*blood ; Prediabetic State/*blood; Adult ; Blood Glucose/metabolism ; C-Peptide/blood ; Case-Control Studies ; Fasting/blood ; Female ; Glucose Clamp Technique ; Glucose Tolerance Test ; Humans ; Insulin/metabolism ; Insulin Resistance/physiology ; Insulin-Secreting Cells/metabolism ; Male ; Middle Aged ; Osteocalcin/metabolism

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/m ² ) and individuals (n = 79) with impaired glucose regulation (IGR) (BMI = 31.9 ± 1.2 kg/m ² ) 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- ³ H-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.

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Keywords: Adiponectin; Beta-cell function; Euglycemic hyperinsulinemic clamp; Glucose metabolism; Human; Impaired fasting glucose; Impaired glucose regulation; Impaired glucose tolerance; Leptin; Osteocalcin; Osteopontin; Osteoprotegerin; Prediabetes; Type 2 diabetes mellitus; Whole body insulin sensitivity

0 (Blood Glucose)
0 (C-Peptide)
0 (Insulin)
0 (Osteoprotegerin)
0 (SPP1 protein, human)
0 (TNFRSF11B protein, human)
104982-03-8 (Osteocalcin)
106441-73-0 (Osteopontin)

Date Created: 20171120 Date Completed: 20180521 Latest Revision: 20181202

20221213

PMC5816090

10.1007/s00592-017-1065-z

29151224