Association between serum osteocalcin and insulin sensitivity in primary hyperparathyroidism
Laura Gianotti, Francesco Tassone, Micaela Pellegrino, Claudia Baffoni, Chiara Giulia Croce, Flora Cesario & Giorgio Borretta
A regulatory role of the skeleton on glucose metabolism has been supposed both in animals and in humans. Osteocalcin (OC) seems to be involved in this regulation and has been reported to be inversely associated with insulin resistance and measures of adiposity in different populations of adult subjects. Primary hyperparathyroidism (PHPT) is a condition mostly affecting elderly subjects and characterized by both marked increased bone turnover and increased insulin resistance. The aim of the study was to evaluate whether OC levels maintained the association with blood markers of insulin resistance and BMI in a large series of subjects with PHPT at the time of the diagnosis. In a consecutive series of 219 patients with PHPT (age, mean±S.E.M., 59.1±13.6 years; BMI: 25.5±5.2 kg/m2; PTH: 200.9±164.8 pg/ml; Ca: 11.1±1.1 mg/dl) we measured serum and urinary bone markers including serum OC, ALP, bone ALP and urinary cross-links as well as fasting insulin and glucose levels. In all patients insulin sensitivity was estimated by homeostatic model assessment (HOMA). In PHPT patients mean serum OC was clearly higher than normal range. After dividing PHPT patients according to glucose tolerance to OGTT, we found that OC was similar in NGT and IGT (52.3±54.7 and 51.2±50.7 ng/ml, respectively) and higher than DM (28.7±20.2 ng/ml, P<0.02 and <0.04 versus NGT and IGT, respectively). In all PHPT patients, OC was negatively associated with fasting glucose (R=−0.24, P<0.0002), while positively with index of insulin sensitivity Homa-2S (R=0.16, P<0.025). After multivariate analysis, among all bone markers, serum OC resulted independently associated with HOMA2S (β −0.031, P<0.02). Our findings show that in PHPT, a condition connoted by high bone turnover and increased OC, the relationship between OC and insulin sensitivity is maintained. These results provide support for a role of OC in regulating glucose tolerance and insulin sensitivity in humans. The protective effect of high OC levels on the PHPT-related diabetogenic risk is still to be established.