Associations between circulating bone-derived hormones osteocalcin, lipocalin 2, and glucose metabolism in patients with acromegaly / 中华内分泌代谢杂志

ABSTRACT

Objective:The aim of this study was to examine the change of serum bone-derived hormones osteocalcin and lipocalin 2 (LCN2) level in patients with active acromegaly, and to further investigate the potential role of osteocalcin and LCN2 in glucose metabolism.Methods:Fifty consecutive patients diagnosed as acromegaly in Nanjing Drum Tower Hospital from December 2016 to August 2018 were recruited. Of those, 41 patients after operations with complete follow-up data were also included. 30 sex, age, and body mass index matched healthy persons as normal controls. Serum osteocalcin and LCN2 levels were compared between controls and patients with acromegaly, as well as at pre- and post- operation periods. Univariate and multivariate linear regression analyses were used to investigate the correlation between bone-derived hormones and glucose metabolism indexes and to determine the independent associations between variables.Results:Compared with normal controls, serum osteocalcin increased [(55.45±34.02 vs 19.46±6.69)ng/ml, P<0.01] and LCN2 levels decreased [(34.15±9.95 vs 57.50±29.75)ng/ml, P<0.01] in patients with acromegaly. Homeostasis model assessment for insulin resistance (HOMA-IR) was also elevated ( P<0.01), but homeostasis model assessment for β cell function (HOMA-β) and area under curve of insulin during 0-120 min of the oral glucose tolerance test (AUC INS) changed non-significantly in acromegaly compared to normal controls ( P>0.05). After operation, with the decrease of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1), serum osteocalcin level decreased [24.79(18.39, 32.59) vs 43.51(26.73, 65.66)ng/ml, P<0.01] and LCN2 level increased [(45.15±15.33 vs 37.03±9.73)ng/ml, P<0.05] significantly compare to pre-operation levels. In a multivariate linear stepwise regression analysis, lean mass was shown to be the only positive predictor for LCN2 ( β=0.44, P=0.015) and elevated serum IGF-1 was a positive predictor for osteocalcin ( β=0.512, P<0.01). In the multivariate models, low LCN2 ( β=-0.398, P=0.017) and elevated serum osteocalcin ( β=0.553, P=0.001) were predictors for AUC INS, osteocalcin was a positive predictor of HOMA- β ( β=0.519, P=0.004). GH ( β=0.294, P=0.029) and IGF-1( β = 0.428, P=0.002) were all identified as positive predictors of HOMA-IR during multivariate testing in acromegaly patients. Conclusions:Acromegaly patients had increased osteocalcin and decreased LCN2 serum levels, and corresponding alteration was detected with the correction of biochemical abnormalities. Serum osteocalcin and LCN2 were predictors of β-cell function in acromegaly patients. This study adds new evidence for the role of bone in regulating glucose metabolism in acromegaly.