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These authors sought
to explore the observation that insulin-like growth factor (IGF)-I
levels remain normal in obesity despite reduced growth hormone (GH)
levels. Ninety-one healthy adults (mean age about 50; range 21-82
years) were subdivided by body mass index (BMI) and gender; there
were 19 normal weight men, 23 normal weight women, 15 obese men and
34 obese women (obesity defined as BMI > 30). Fat mass and percent
body fat were measured by bioimpedance. GH sensitivity was assessed
by an IGF-I generation test, with IGF-I levels measured before and 24
hours after a single, standard 7mg dose (21IU) of GH. The increment
in IGF-I was greater in obese than normal-weight equivalents,
negatively correlated with baseline IGF-I concentration, positively
correlated with GH binding protein (GHBP) level, and seen in both men
and women (pre- and post-menopausal). GHBP concentrations were higher
in obesity, and also correlated with BMI, fat mass and percent body
fat. The authors concluded that their study provides evidence of
increased GH sensitivity in obesity. The fact they used a single,
standard GH dose makes the result cleaner than earlier studies that
employed a weight-based GH dosing scheme; IGF-I levels were higher in
obese subjects, but in those studies, the obese subjects also
received a greater GH dose. Because GHBP is the extracellular domain
of the GH receptor (GHR), it is sometimes used as an indirect measure
of GHR number. The finding of a positive association between GHBP
level, markers of obesity and IGF-I increment led the authors to
hypothesize that the enhanced GH sensitivity of obesity may be due to
increased GHR density, itself resulting from the lower GH levels.
Because the data are all associative, further studies are needed to
test this hypothesis.
Gleeson
HK, Lissett CA, Shalet SM. IGF-I response to a single bolus of growth
hormone is increased in obesity. J Clin Endocrinol Metab
2005;90:1061-7.
Editor’s
Comment: This paper clearly showed increased hepatic sensitivity
to GH in obesity, at least in terms of IGF-I generation, which helps
to explain the discordance between the low GH but normal IGF-I levels
seen in obesity. The pediatric correlate of this adult study is the
enhanced growth frequently experienced by obese children who continue
growing despite GH deficiency (classically, craniopharyngioma
patients who develop hypothalamic obesity and GH deficiency); the
growth without GH phenomenon is reviewed in Reference 1. Proposed
mechanisms include hyperinsulinism-stimulated growth, decreased
IGFBP-1 levels resulting in increased bioavailable (free) IGF-I, and
increased growth plate stimulation by sex steroids (increased
aromatization by the greater adipose mass). An interesting finding
came from studies of a model of endochondral ossification, the
chondrocyte population of the skeletal growth centers in the mouse
mandibular condyle. The growth center chondrocytes expressed leptin
receptors and when stimulated by leptin, increased expression of
IGF-I receptor, increased both proliferation and differentiation
processes, and had larger growth plate growth.2
Furthermore, when mice were calorie-restricted by 40%, circulating
IGF-I levels dropped by 70% and tibial growth decreased by 5%; leptin
treatment corrected the growth deficit despite further reductions in
circulating IGF-I levels.3 Thus, the growth-promoting
consequences of obesity are multi-factorial, and it will be
interesting to see if enhanced hepatic GH sensitivity, perhaps due to
increased GHR density, also plays a role in the growth of obese
children.
Adda Grimberg, MD
References - (linked to  )
- Phillip M, Moran O, Lazar L. J Pediatr Endocrinol Metab 2002;15 Suppl 5:1267-72.
- Maor G, Rochwerger M, Segev Y, Phillip M. J Bone Miner Res 2002;17:1034-43.
- Gat-Yablonski G, Ben-Ari T, Shtaif B, et al. Endocrinology 2004;145:343-50.
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Current GGH - Vol. 24 No. 1
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