Associations between circulating bone-derived hormones lipocalin 2, osteocalcin, and glucose metabolism in acromegaly

J Endocrinol Invest. 2020 Sep;43(9):1309-1316. doi: 10.1007/s40618-020-01221-9. Epub 2020 Mar 20.

Abstract

Purpose: The aim was to examine changes in the bone-derived hormone lipocalin 2 (LCN2) levels in patients with active acromegaly and to investigate the potential roles of LCN2 and osteocalcin in glucose metabolism.

Methods: We recruited 50 consecutive acromegalic patients. Of those, 39 patients with complete postoperative follow-up data were included. Thirty sex-, age-, and BMI-matched healthy individuals were recruited as normal controls. The pre- and postoperative serum LCN2 and osteocalcin levels were compared. The homeostasis model assessment insulin resistance (HOMA-IR) index and secretion [β-cell function (HOMA-β)] were calculated.

Results: Compared with controls, acromegalic subjects had lower LCN2 levels (34.15 ± 9.95 vs 57.50 ± 29.75 ng/mL, P < 0.01) and higher osteocalcin levels (55.45 ± 34.02 vs 19.46 ± 6.69 ng/mL, P < 0.01). Acromegalic patients also had elevated HOMA-IR levels, and the HOMA-β and the area under the curve for insulin (AUC INS) levels were slightly but nonsignificantly increased. The serum levels of LCN2 significantly increased after surgery (37.03 ± 9.73 vs 45.15 ± 15.33 ng/mL, P < 0.05), and those of osteocalcin significantly decreased [43.51 (26.73-65.66) vs 24.79 (18.39-32.59) ng/mL, P < 0.01]. Total lean mass was the only positive predictor of LCN2, and elevated serum IGF-I was a positive predictor of osteocalcin. Low LCN2 and elevated serum osteocalcin levels were predictors of the AUC INS, and osteocalcin was a positive predictor of HOMA-β.

Conclusion: The bone-derived hormones, osteocalcin and LCN2 changed significantly in active acromegaly, were altered after treatment and served as predictors of β-cell function in acromegaly. This study shows that the bone could be involved in regulating glucose metabolism in acromegaly.

Keywords: Acromegaly; Glucose metabolism; LCN2; Osteocalcin.

MeSH terms

  • Acromegaly / blood*
  • Adult
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Bone and Bones / metabolism
  • Carbohydrate Metabolism
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • Glucose / metabolism*
  • Humans
  • Insulin Resistance / physiology
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / metabolism
  • Lipocalin-2 / blood*
  • Male
  • Middle Aged
  • Osteocalcin / blood*

Substances

  • BGLAP protein, human
  • Blood Glucose
  • LCN2 protein, human
  • Lipocalin-2
  • Osteocalcin
  • Insulin-Like Growth Factor I
  • Glucose