Context: Growth hormone (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, ß-cell function and body composition change over time after stop of GH treatment.

Objective: To investigate longitudinal changes in Si, ß-cell function and body composition after stop of long-term GH treatment.

Design: Longitudinal study.

Patients: 48 SGA adolescents were studied at adult height, while still on GH, and 6 months after GH stop, and compared with 38 AGA controls at both time points.

Outcome measure: Paired measurements of Si and ß-cell function, assessed by frequently sampled intravenous glucose tolerance tests (FSIGT) with Tolbutamide, and body composition, measured by dual energy x-ray absorptiometry (DXA).

Results: After stop of GH, Si (p=0.006), glucose effectiveness (Sg; p=0.009) and ß-cell function (disposition index = DI; p=0.024) increased, whereas insulin secretion (AIR; NS) decreased. Fat percentage increased (p<0.0005), and lean body mass (LBM) 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, AIR was higher at both time points, and Sg and DI became higher.

Conclusions: The GH-induced lower insulin sensitivity in SGA adolescents increases after stop of 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 LBM, without changes in fat distribution.