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

Abstract

Background/Aims: Adipose tissue (AT) distribution is closely related to metabolic disease risk. Growth hormone (GH) reduces visceral and total body fat mass and induces whole-body insulin resistance. Our aim was to assess the effects of total and visceral AT (VAT) distribution and derived adipokines on systemic insulin resistance and lipid metabolism in acromegaly. Methods: Seventy adult patients with active acromegaly (43 males, age 49 ± 14 years) were evaluated before treatment, and a subset (n = 30, 20 males) was evaluated after treatment for acromegaly. Body composition and VAT, glucose metabolism parameters, lipids, C-reactive protein, and selected adipokines (vaspin, omentin, adiponectin, and leptin) were measured. Results: At baseline, VAT was positively associated with glucose metabolism parameters and with lipids. GH, but not IGF-I, was negatively associated with all AT depots (visceral, trunk, limbs, and total; 0.41 ≤ r ≤ 0.61, p < 0.001 for all) and positively associated with vaspin (r = 0.31, p = 0.013). The fat deposition after treatment was predominantly located on trunk and visceral depots. The lipid profile partially improved, with increases in HDL and apolipoprotein A-I and a decrease in lipoprotein(a). Vaspin decreased and omentin increased. Adiponectin and leptin did not change significantly. The improvement in homeostasis model assessment for insulin resistance (HOMA-IR) was best predicted by the decreases in IGF-I and vaspin and the lack of an increase in trunk fat (R² = 0.59, p = 0.001). Conclusions: (1) VAT is a metabolic risk factor for patients with active acromegaly; (2) vaspin and omentin levels are influenced by the disease activity but are not associated with VAT mass; (3) fat deposition after treatment occurs predominantly on the trunk and in visceral depots, and (4) insulin resistance decreases and the lipid profile partially improves with treatment.

Changes in the management and comorbidities of acromegaly over three decades: the French Acromegaly Registry

“…Elevated IGF-I levels were associated with T2DM, independently of age and BMI. A number of metabolic parameters, such as fasting glucose, HbA1C and serum triglycerides, improved significantly during follow-up, confirming previous publications (41). Of note, mean BMI and body weight were higher at the last visit than at diagnosis, as reported elsewhere (42).…”

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

“…For example, as TBS is computed from DXA images, any image "noise" can influence the TBS evaluation and excessive soft tissue in the abdomen, overlying the region of interest, may reduce the TBS estimate. It is known that with treatment of acromegaly, although BMI remains unchanged, the patients do accumulate fat, predominantly in the central depots (20,41), and this can interfere with TBS estimates and lead to a measurement of a false decrease in TBS.…”

“…Some technical limitations of TBS analyses should however be noted. Additional studies, both technical and clinical, should be performed to assess the advantages and limitations of the TBS in order to ensure that it is used appropriately, also in acromegaly, where the disease by itself, but also treatment will have major impact not only on bone tissue but also on surrounding tissue (20). In order to mitigate this problem in vivo, the TBS calculation is adjusted for BMI.…”

A Functional Interplay between IGF-1 and Adiponectin

“…A hallmark of active acromegaly is an alteration of the distribution of the adipose tissue, mainly characterized by a decrease in fat mass, an increase in lean mass, and an ectopic extra-adipose tissue deposition [ 76 , 77 , 78 ]; such a condition determines an impaired insulin action in both hepatic and extra-hepatic tissues [ 79 ]. In this regard, Olarescu et al reported an elevated metabolic activity for adipose tissue in acromegaly, able to affect the production and the secretion of adipokines [ 76 , 77 , 78 ]. As for adiponectin, data are controversial in active acromegaly, as quoted above, but recently White et al proved the negative regulator effect of STAT5A transcription factor on the adiponectin expression in murine 3T3-L1 preadipocytes after GH treatment [ 80 ].…”