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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

Departments of Medicine (P.U.F., C.M.R.-V.) and Neurosurgery (J.N.B.), Columbia University College of Physicians and Surgeons, New York, New York 10032; Obesity Research Center St. Luke’s-Roosevelt Hospital (W.S., S.B.H., D.G.), Columbia University, New York, New York 10025; Department of Medicine (E.B.G.), Mt. Sinai Medical Center, New York, New York 10029; and Merck Research Laboratories (S.B.H.), Rahway, New Jersey 07065

Address all correspondence and requests for reprints to: Pamela U. Freda M.D., Department of Medicine, Columbia University, College of Physicians and Surgeons, 650 West 168th Street, 9-905, New York, New York 10032. E-mail: puf1{at}columbia.edu.

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.