Abstract

Lipocalin-2 (LCN2) is a secreted glycoprotein, member of the lipocalin superfamily and mediator of several chronic inflammatory processes. Metabolic syndrome (METs) and total growth hormone deficiency (GHD) are known as chronic inflammatory conditions (1,2). While discrepant results have been found in literature on LCN2 plasmatic levels in metabolic syndrome, no studies have been performed in GHD. Partial growth hormone deficiency (pGHD) either is associated with cardiovascular risk (3). Therefore, the primary end-point of this observational cross-sectional study was to compare LCN2 in these clinical settings, trying to assess its possible role as a biomarker in these diseases, whether the secondary end-point was to evaluate the impact of BMI and indexes of insulin sensitivity/resistance on this protein plasmatic levels. 74 patients were included in the study. They were divided as follows: Group A, METs (18 patients, 13 females and 5 males, mean±SEM age 45.1±4.11 ys, BMI 31.22±1.73 kg/m2); Group B, GHD (18 patients, 8 F and 10 M, mean±SEM age 52.44±2.61 ys, BMI 30.49±1.87 kg/m2); Group C, Partial GHD (19 patients, 13 F and 6 M, mean±SEM age 48.63±2.19 ys, BMI 29.11±1.85 kg/m2); Group D, Controls (19 patients, 13 F and 6 M, mean±SEM age 40.26±2.87 ys, BMI 23.25±0.95 kg/m2). The diagnosis of metabolic syndrome was made according to NCEP ATPIII criteria (2005 revision). GHD was diagnosed with dynamic test using Growth Hormone-Releasing Hormone (GHRH 50 μg i.v. + arginine 0,5 g/Kg), with a peak GH response between 9 and 16 μg/L when BMI was < 30 kg/m2 or 4 and 9 μg/L when BMI was > 30 kg/m2. Partial GHD was defined with dynamic test using GHRH, with a peak GH response < 9 μg/L when BMI was < 30 kg/m2 or < 4 μg/L when BMI was > 30 kg/m2.They were evaluated for: serum glucose and insulin, HOMA-index, QUICKI-index, Total/LDL/HDL cholesterol, triglycerides, IGF-1 and LCN2 (measured using ELISA kit DuoSet LCN2/NGAL, R&D systems).LCN2 plasmatic levels were significantly increased in METs, while no difference with control group was found in total and partial GHD. LCN2 levels were not influenced by BMI and HOMA-index. A significant positive correlation between LCN2 and HOMA-index was found in controls, while a trend-like, yet not significant, positive correlation was evidenced in partial GHD. No correlations between these parameters were identified in METs and GHD groups. Our data support the hypothesis that LCN2 plasmatic levels increase in metabolic syndrome. As previously shown (4), different inflammatory patterns characterize the two pathological conditions. However, the correlation between HOMA index and LCN2 suggest a possible modulatory action of LCN2 on insulin resistance in normal subjects and partial GHD ones. (1): Esser et al, Diab Res Clin Prac, 105(2):141–50, 2014.(2): Caicedo et al, Int J Mol Sci, 19(1), 2018.(3): Colao et al, JCEM, 91(6):2191–200, 2006.(4): Mancini et al, Endocrine, 59(1):130–136, 2018.

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