Decreased GH secretion and increased GH clearance contribute to low GH levels found in obesity; in spite of which IGF-1 levels are reported as normal. To explain the discordancy between GH and IGF-1 status in obese subjects, an increase in peripheral (hepatic) sensitivity to GH activity has been hypothesized. Previously peripheral responsiveness to GH in obesity has been investigated and reported to be increased, however the use of weight-based GH doses made interpretation difficult. Therefore we have pursued this question further by challenging a large cohort of healthy normal weight and obese subjects with a non-weight-based dose of GH.
91(34 male) healthy subjects were divided into age matched groups, men and women with a BMI <30 (normal weight men (NM)(BMI 25.7(21.6-29.4)kg/m2)(n=19) and women (NW)(24(18.8-28.9)kg/m2)(n=23) and with a BMI >30 (obese men (OM)(41(30.3-71.7)kg/m2)(n=15) and women (OW)(43.1 (30.1-67.6)(n=34)). Fat mass (FM) and percentage fat (F%) were measured using a bioelectrical impedance analyser. An IGF-1 generation test, which involves a sc injection of 21IU(7mg) of GH, was performed. At baseline serum samples were assayed for GHBP. Serum IGF-1 levels were measured at baseline and 24 hours after GH administration.
GHBP levels were significantly higher in the obese groups than in the equivalent normal weight groups. GHBP levels correlated highly with BMI, F% and FM(R>0.6, p<0.0001). Neither baseline nor peak IGF-1 level was affected by body composition. There was a higher increment IGF-1 in obese subjects compared with the equivalent normal weight subjects (NMvsOM:245(33-342)vs 291(192-427)ng/ml(p<0.05); NWvsOW:220(103-435)vs 315(144-450)ng/ml(p<0.0005)). Peak IGF-1 was positively correlated with baseline IGF-1(F=110.8) with an additional positive effect of GHBP(F=18.2)(R2=0.61). Increment of IGF-1 was negatively correlated with baseline IGF-1(F=12.1) and positively correlated with GHBP(F=18.2)(R2=0.29).
In conclusion in obese individuals there is a larger increment of IGF-1 to an acute bolus of GH. Increment and peak IGF-1 are associated positively with GHBP level which in turn is associated with markers of increasing obesity. GH responsiveness is increased in obesity.
22 - 24 Mar 2004
British Endocrine Societies