SERUM LEPTIN IS INCREASED IN GROWTH HORMONE-DEFICIENT ADULTS - RELATIONSHIP TO BODY-COMPOSITION AND EFFECTS OF PLACEBO-CONTROLLED GROWTH-HORMONE THERAPY FOR 1 YEAR

The gene product from the ob gene, leptin, has recently been character ized in humans, The circulating level of leptin is related to body mas s index (BMI) and more closely to estimates of total body fat, whereas visceral fat has been reported to be of minor importance, However, it is unknown if leptin is directly regulated by hormones that influence substrate metabolism and body composition. We studied leptin in adult growth hormone (GH)-deficient (GHD) patients substituted with GH trea tment for 12 months in a parallel double-blind, placebo-controlled stu dy. Twenty-seven GHD adults aged 44.9 +/- 1.9 years underwent anthropo metric measurements for determination of regional and total body fat ( BMI, waist to hip ratio [WHR], computed tomographic [CT] scan, dual-en ergy x-ray absorptiometry [DEXA] scan, and bioimpedance analysis [BIA] ) before and after 12 months of placebo-controlled GH substitution (2 IU/m(2)) in a parallel design, The same measurements were performed in 42 healthy adults aged 39.1 +/- 1.7 years. The logarithm of serum lep tin levels correlated positively with abdominal subcutaneous fat and t otal body fat (BIA and DEXA) in untreated GHD patients and healthy sub jects. Fasting insulin did not correlate with leptin levels in either of the groups, After 12 months of GH administration, the body composit ion of GHD patients was significantly changed with respect to a marked decrease in body fat, The relations of leptin to the estimates of bod y fat were maintained, and leptin was furthermore related to BMI and f asting insulin. In multiple linear regression analyses, additional est imates of visceral adiposity (intraabdominal fat and maximal anterior- posterior diameter determined by CT scan) were significant determinant s of leptin in the healthy subjects, The increase in fasting insulin l evels during GH substitution correlated negatively with the reduction in leptin levels (r = -.823, P = ,003), At baseline, leptin levels wer e increased in the patients compared with controls in both sexes (wome n, 21.8 +/- 3.3 v 11,3 +/- 1.4 ng/mL, P = .002; men, 8.1 +/- 1,2 v 4.7 +/- 0.7 ng/mL, P =.008). Leptin levels were similar in GHD patients t reated for 12 months compared with healthy controls for both women and men (women, 15.9 +/- 2.3 and 11.3 +/- 1.4 ng/mL, P =.163; men, 7.1 +/ - 2.8 and 4.7 +/- 0.7 ng/mL P = .759), In healthy adults and in GHD pa tients, leptin levels were significantly higher in women than in men ( 11.3 +/- 1.4 v 4.7 r 0.7 ng/mL, P <.001;21.8 +/- 3,3 v 8.1 +/- 1.2 ng/ mL, P <.001). Gender remained a significant determinant of leptin leve ls in several models of multiple linear regression analysis also inclu ding age, estradiol levels, insulin, and estimates of body fat, We con clude that leptin is increased but not differently regulated in GHD pa tients compared with normal subjects, and that leptin levels are close ly related to estimates of body fat. This relationship is maintained d uring a decrease in body fat due to GH substitution, Copyright (C) 199 7 by W.B. Saunders Company.