Reduced GH levels are found in obesity; in spite of which IGF-1 levels are reported as low normal or normal. Previously peripheral responsiveness to GH has been investigated and reported to be increased in obese men and premenopausal women, however the use of weight-based GH doses in these studies made data interpretation difficult. Growth hormone binding protein (GHBP) measurement constitutes an indirect estimate of GH receptor number. GHBP has been reported to be elevated in obesity, however, results from a recent study implied that this was only in men and premenopausal, but not postmenopausal women. Therefore we have pursued this question further by challenging a cohort of healthy normal weight and obese subjects with a non-weight-based dose of GH and examined the relationship of GHBP with the IGF-1 response in the context of their body composition.

98 (40 male) healthy subjects with a wide range of ages and BMI were studied. 91 (34 male) of these subjects were divided into groups of similar age, men and women with a BMI<30 (normal weight men (NM) (BMI 26 (22-29) kg/m2) (n = 19) and women (NW) (24 (19-29) kg/m2) (n = 23) and with a BMI>30 (obese men (OM) (41 (30-72) kg/m2) (n = 15) and women (OW) (43 (30-68) kg/m2) (n = 34)). Fat mass (FM) and percentage fat (F%) were measured by a bioelectrical impedance analyser. An IGF-1 generation test, which involved a sc injection of 21IU (7 mg) of GH, was performed. At baseline serum samples were assayed for GHBP; serum IGF-1 and IGFBP3 levels were measured both at baseline and 24 h after GH administration.

There was a higher increment IGF-1 in obese men and women compared with the equivalent normal weight subjects (NM vs. OM: 245 (33-342) vs. 291 (192-427) ng/ml (P < 0.05); NW vs. OW: 220 (103-435) vs. 315 (144-450) ng/ml (P < 0.0005)). Increment IGF-1 was negatively correlated with baseline IGF-1 (F=12.1) and positively correlated with GHBP (F=18.2) (R2 = 0.29). GHBP levels were significantly higher in the obese men and women (pre- and postmenopausal) than in the equivalent normal weight groups (NM vs. OM: 2175 (995-4190) vs3030 (1540-5470) pmol/L (P < 0.05); NW vs. OW: 2131 (1010-5040) vs. 3585 (1540-5740) pmol/L (P < 0.0005)). GHBP levels correlated highly with BMI, F% and FM (R>0.6, P < 0.0001). Baseline IGF-1 was not affected by body composition.

In conclusion in obese compared with normal weight healthy subjects there is a larger increment IGF-1 to a single bolus of GH in men, and irrespective of menopausal status, women. Increment IGF-1 is associated positively with GHBP level which in turn is associated with markers of increasing obesity in men and women. GH responsiveness is increased in obesity.