Longitudinal changes in insulin sensitivity and body composition of small-for-gestational-age adolescents after cessation of growth hormone treatment.
BACKGROUND
GH treatment reduces insulin sensitivity (Si). For small-for-gestational-age (SGA) subjects, who might have an increased risk to develop cardiovascular disease and type 2 diabetes, it is still uncertain how Si, beta-cell function, and body composition change over time after stopping GH treatment.


OBJECTIVE
Our objective was to investigate longitudinal changes in Si, beta-cell function, and body composition after cessation of long-term GH treatment.


METHODS
We conducted a longitudinal study that included 48 SGA adolescents studied at adult height, while still on GH, and 6 months after GH stop and compared them with 38 appropriate-for-gestational-age (AGA) controls at both time points.


METHODS
We took paired measurements of Si and beta-cell function, assessed by frequently sampled iv glucose tolerance tests with tolbutamide, and body composition, measured by dual-energy x-ray absorptiometry.


RESULTS
After stopping GH, Si (P = 0.006), glucose effectiveness (Sg; P = 0.009) and beta-cell function (disposition index; P = 0.024) increased, whereas insulin secretion (acute insulin response; not significant) decreased. Fat percentage increased (P < 0.0005), and lean body mass decreased (P < 0.0005), but fat distribution remained unaltered, and body composition remained within the normal range. Compared with AGA controls, Si was lower during GH and became similar after GH stop, acute insulin response was higher at both time points, and glucose effectiveness and disposition index became higher.


CONCLUSIONS
The GH-induced lower Si in SGA adolescents increases after stopping long-term GH treatment and becomes similar to that of AGA controls. Discontinuation of GH treatment is, however, also associated with an increase in percent body fat and with a decrease in lean body mass, without changes in fat distribution.
Willemsen
Ruben H
RH
Department of Pediatrics, Division of Endocrinology, Erasmus Medical Center Sophia, GJ Rotterdam, The Netherlands. r.h.willemsen@erasmusmc.nl
Willemsen
Sten P
SP
Hokken-Koelega
Anita C S
AC
D000293:Adolescent; D001823:Body Composition / Q000187:drug effects*; D001827:Body Height / Q000187:drug effects / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006130:Growth Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development*; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology; D008137:Longitudinal Studies; D008297:Male; D028761:Withholding Treatment
D019382:Human Growth Hormone