Lower visceral and subcutaneous but higher intermuscular adipose tissue depots in patients with growth hormone and insulin-like growth factor I excess due to acromegaly

Abstract

Context: GH and IGF-I are important regulators of metabolism and body composition. In acromegaly, a state of GH and IGF-I excess, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) distribution.

Objectives: Our objective was to test the hypothesis that in acromegaly whole-body AT mass is less and to examine for the first time the relationship between GH/IGF-I excess and intermuscular AT (IMAT), an AT depot associated with insulin resistance in other populations.

Design, setting, and patients: We conducted a cross-sectional study in 24 adults with active acromegaly compared with predicted models developed in 315 healthy non-acromegaly subjects.

Outcome measures: Mass of AT in the visceral AT (VAT), sc AT (SAT), and IMAT compartments from whole-body magnetic resonance imaging and serum levels of GH, IGF-I, insulin, and glucose were measured.

Results: VAT and SAT were less in active acromegaly (P < 0.0001); these were 68.2 +/- 27% and 79.5 +/- 15% of predicted values, respectively. By contrast, IMAT was greater (P = 0.0052) by 185.6 +/- 84% of predicted. VAT/trunk AT ratios were inversely related to IGF-I levels (r = 0.544; P = 0.0054). Acromegaly subjects were insulin resistant.

Conclusions: VAT and SAT, most markedly VAT, are less in acromegaly. The proportion of trunk AT that is VAT is less with greater disease activity. IMAT is greater in acromegaly, a novel finding, which suggests that increased AT in muscle could be associated with GH-induced insulin resistance. These findings have implications for understanding the role of GH in body composition and metabolic risk in acromegaly and other clinical settings of GH use.

Figure 1

Mean VAT in subjects with active acromegaly (patterned bar) and their VAT predicted by the model (solid bar) shown separately for females, males, and the total group of subjects with moderate/severe acromegaly (n = 22). VAT was significantly below predicted VAT in the females alone (*, P = 0.04), males alone (**, P = 0.002), and the total group of subjects with active acromegaly (***, P < 0.001).

Figure 2

Mean SAT in subjects with active acromegaly (patterned bar) vs. their SAT predicted by the model (solid bar) shown separately for females, males, and the total group of subjects with moderate/severe acromegaly (n = 22). SAT was significantly below predicted in the females alone (*, P = 0.006), the males alone (**, P = 0.0018), and in the total group of subjects with active acromegaly (***, P < 0.001).

Figure 3

Mean IMAT in subject with active acromegaly (patterned bar) shown in relation to their IMAT predicted by the model (solid bar) shown separately for females, males and the total group of subjects with acromegaly (n = 20 non-Hispanic subjects). Females alone showed a trend for IMAT to be above predicted (*, P = 0.067). IMAT was significantly elevated above predicted in the males alone (**, P = 0.002) and in the total group (***, P = 0.003).

Figure 4

Ratio of VAT to trunk AT vs. serum IGF-I levels in subjects with active acromegaly. Rising serum IGF-I levels are inversely related to the proportion of trunk AT that is VAT (r = 0.544; P = 0.006).