Background/Aim: In children with Prader-Labhart-Willi syndrome (PWS), the insulin secretion is reduced, despite obesity, being ascribed to the growth hormone (GH) deficiency of hypothalamic origin. Besides, an increased prevalence of diabetes mellitus was described in this syndrome. Hence, we addressed the questions of how body composition and insulin secretion are interrelated and what impact GH therapy has on the carbohydrate metabolism in PWS. Methods: We measured weight, lean and fat mass (by dual-energy X-ray absorptiometry), triglycerides, HbA<sub>1c</sub>, and fasting insulin and glucose levels in 17 children (age range 1.5–14.6 years) with PWS to examine whether the carbohydrate metabolism is altered during 36 months of therapy with 8 mg GH/m<sup>2</sup> body surface/week. In a subgroup of 8 children, the insulin secretion was longitudinally assayed during oral glucose tolerance at 0 and 12 months of therapy. Results: Before therapy, the insulin secretion was lower and markedly delayed as compared with reference data and did not rise during therapy. The glucose tolerance was impaired in 2 of 12 children examined by oral glucose tolerance test before therapy and normalized during therapy. Fasting insulin and insulin resistance being normal at the beginning, significantly increased at 12 months and returned to initial levels at 36 months of GH therapy. Fasting glucose as well as HbA<sub>1c</sub> and triglyceride levels were always normal. The fat mass before GH therapy was increased (39.5%) and dropped into the upper normal range (28.3%) during 3 years of therapy, being correlated with fasting insulin concentration and indices of insulin sensitivity before and after 1 year of therapy. Conclusions: Children with PWS are characterized by an intact insulin sensitivity with a decrease and a delay of insulin secretion, regardless of moderate obesity or GH treatment. In the present setting, the carbohydrate metabolism is not impaired by GH therapy, but by the excessively increased fat mass.