Extended Abstract Low birth weight has been associated with impaired insulin sensitivity,
type 2 diabetes mellitus, hypertension and cardiovascular disease in later life. GH
therapy is known to increase fasting and postprandial insulin levels. For this reason
concern has been expressed regarding the possible detrimental effects of GH therapy
in children born small for gestational age (SGA). To assess the effects of GH therapy
on body composition, carbohydrate metabolism and final height in short SGA children,
165 prepubertal short children born SGA were enrolled in either a multicentre, double-blind,
randomized, dose-response GH trial (n = 75) or in a GH controlled trial (n = 90).
The inclusion criteria were: (1) birth length standard deviation score (SDS) below
–2; (2) age 3–8 years; (3) height SDS below –2. The children’s mean (SD) age was 7.3
(2.1) years (GH dose-response trial) and 6.0 (1.5) years (GH controlled trial), birth
length SDS was –3.6 and height SDS was –3.0 (0.7). In the GH dose-response trial,
children were randomly assigned to either 1 mg GH/m<sup>2</sup> per day (group A,
n = 41) or 2 mg GH/m<sup>2</sup> per day (group B, n = 38) (≈0.033 or 0.067 mg/kg
per day, respectively). In the GH controlled trial, children were randomly assigned
to 1 mg GH/m<sup>2</sup> per day (n = 60) or served as controls (n = 30). Subjects
underwent standard oral glucose tolerance tests and measurement of body mass index,
systolic and diastolic blood pressure and serum lipids at baseline and after 1 and
6 years of GH therapy and again 6 months after discontinuation of GH. Body composition
was measured by dual energy x-ray absorptiometry at baseline and again after 3 years
in the GH controlled trial. Mean (SD) final height SDS was not significantly different
between the two GH dosage groups: –1.2 (0.7) in group A and –0.8 (0.7) in group B.
At the start of GH therapy, 8% of children had impaired glucose tolerance (IGT). Systolic
blood pressure was significantly higher in comparison with healthy peers. GH therapy
induced considerably higher fasting and glucose-stimulated insulin levels after 1
and 6 years, regardless of GH dosage. After 6 years, 4% of children had IGT. Six months
after discontinuation of GH, glucose levels remained normal, whereas fasting and glucose-stimulated
insulin returned to levels comparable to those of healthy peers. None of the children
developed diabetes. During 6 years of GH therapy both systolic and diastolic blood
pressure decreased significantly and remained so after discontinuation of GH therapy.
At baseline all children had reduced bone mineral content and lean body mass. Fat
mass was not significantly lower than normal. Treatment with 1 mg GH/m<sup>2</sup>
per day resulted in a significant increase in (and normalization of) bone mineral
content and lean body mass in comparison with untreated short SGA controls. Fat mass
decreased during the first year of GH but returned to values comparable to those at
baseline in the following 2 years of GH therapy. We found that long-term, continuous
GH therapy in short children born SGA leads to a normalization of height during childhood
and to a normal final height in most children, regardless of GH dosage. Only very
short or relatively older children may need a dosage of 2 mg GH/m<sup>2</sup> per
day. Long-term GH therapy had no adverse effects on glucose levels and serum lipids
and had a positive effect on blood pressure, even with GH dosages of up to 2 mg/m<sup>2</sup>
per day. However, as has been reported in other patient groups, GH induced higher
fasting and glucose-stimulated insulin levels, indicating insulin resistance. After
discontinuation of GH serum insulin levels returned to normal age-reference levels.
Short SGA children have a reduction in bone mineral content and lean body mass when
compared with healthy controls, which significantly improved (normalized) with GH
therapy at a dose of 1 mg/m<sup>2</sup> per day.