Inflammatory adipokines contribute to insulin resistance in active acromegaly and respond differently to different treatment modalities

Abstract

Background: Active acromegaly is associated with insulin resistance, but it is uncertain whether inflammation in adipose tissue is a contributing factor. Aim: To test if GH/IGF1 promotes inflammation in adipocytes, and if this is relevant for systemic insulin resistance in acromegaly. Furthermore, to investigate the effect of treatment modalities (transsphenoidal surgery (TS), somatostatin analogs (SAs), and pegvisomant (PGV)) on glucose metabolism and inflammatory biomarkers in acromegaly. Methods: The in vitro effects of GH/IGF1 on gene expression of adipokines in human adipocytes were investigated. Body composition, glucose metabolism, and circulating adipokines (adiponectin (AD), high-molecular weight AD (HMWAD), leptin, vascular endothelial growth factor-A (VEGF-A), monocyte chemotactic protein 1 (MCP1), and thioredoxin (TRX)) were measured in 37 patients with active acromegaly before and after treatment. Results: In vitro GH, but not IGF1, increased VEGF and MCP1 in human adipocytes. In all treatment groups, body fat increased and IGF1 decreased to the same extent. Fasting glucose decreased in the TS (PZ0.016) and PGV (PZ0.042) groups, but tended to increase in the SA group (PZ0.078). Insulin and HOMA-IR decreased in both TS and SA groups, while the PGV group showed no changes. Serum VEGF and MCP1 decreased significantly in the TS group only (PZ0.010, PZ0.002), while HMWAD increased with PGV treatment only (PZ0.018). A multivariate analysis model identified the changes in GH and VEGF as predictors of improvement in HOMA-IR after treatment (R

Adiponectin and Cardiac Hypertrophy in Acromegaly

“…The effect of GH-reducing therapy on serum adiponectin levels has also been studied [21,22]. Olarescu et al measured adipokines in 37 patients with active acromegaly before and after treatment.…”

“…In the transsphenoidal surgery (TS) group, adiponectin, vascular endothelial growth factor-A (VEGF-1), monocyte chemotactic protein 1 (MCP1), and thioredoxin (TRX) decreased significantly. In the somatostatin analogs (SA), group leptin increased, while in the pegvisomant (PGV) group HMWAD increased significantly [21]. Silha et al found increased, rather than decreased, adiponectin levels in a study involving 18 patients with acromegaly compared to BMI-and sex-matched controls.…”

“…Indeed, adiponectin levels in acromegalic patients have been reported variably as higher than [18] or similar to [19,20] those in normal controls. The effect of GH-reducing therapy on serum adiponectin levels has also been studied [21,22]. The relationship between adiponectin levels and cardiac parameters has not been studied.…”

The Metabolic Risk in Patients Newly Diagnosed with Acromegaly Is Related to Fat Distribution and Circulating Adipokines and Improves after Treatment

“…Successful surgical and pharmacological treatments for acromegaly improve insulin resistance and the unfavorable lipid profile but increase fat mass [9,14,15,16,17,18]. In the general population, there is an association between the quantity of VAT and metabolic risk, but it is currently unknown whether a decreased fat mass, especially in visceral locations, has an influence on the metabolic risk profile in patients with acromegaly.…”

Serum visfatin levels in acromegaly: Correlation with disease activity and metabolic alterations

“…The white visceral adipose tissue produces different mediators, the adipokines, and a strong association between metabolic risk and fat distribution or adipokine levels has recently been documented [6]. The adipose dysfunction, resulting in higher lipolytic activity, changes the production and secretion of adipokines known to play a role in the pathogenesis of low-grade systemic inflammation and insulin resistance [7], leading to a cardiovascular disease and systemic metabolic complications [8,9]. In this view, the relation between GH and adipokine levels could explain the metabolic risk associated with acromegaly, although to date the data on adipokine levels in acromegaly are discordant.…”