Effect of discontinuation of growth hormone treatment on risk factors for cardiovascular disease in adolescents born small for gestational age

Hyperlipidemia, diabetes mellitus type 2, and coronary heart disease have been associated with being born small for gestational age (SGA). It has been reported that GH treatment induced higher insulin levels, which has led to concern regarding the long-term effect of GH treatment in predisposed individuals such as children born SGA. In this study, we assessed the effect of discontinuation of long-term GH treatment in 47 adolescents born SGA on oral glucose tolerance tests, blood pressure (BP), and serum lipid levels for two GH dosage groups (3 vs. 6 IU/m2 x d). At 6 months after discontinuation of GH treatment mean (SD) age was 16.0 (2.1) yr. Mean duration of GH treatment had been 6.9 (1.5) yr. Fasting glucose levels and 120-min area under the curve for glucose 6 months after discontinuation of GH treatment showed no difference from pretreatment levels for both GH dosage groups. After discontinuation of GH treatment, fasting insulin levels returned to pretreatment levels (8.4 mU/liter), whereas the 120-min area under the curve for insulin decreased, compared with 6-yr levels (P < 0.01), regardless of GH dosage group. No significant difference was found when levels were compared with a control group. In addition, for both GH dosage groups, no significant changes in systolic and diastolic BP SD score, total cholesterol, and atherogenic index (total cholesterol/high-density lipoprotein cholesterol) were seen from 6 yr of GH until 6 months after discontinuation of GH treatment. In conclusion, in children born SGA, the GH-induced insulin insensitivity disappeared after discontinuation of GH, even after long-term GH treatment. Furthermore, the beneficial effect of GH on BP was not changed after discontinuation of GH, and most children had normal lipid levels

Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial

The GH dose-response effect of long-term continuous GH treatment on adult height (AH) was evaluated in 54 short children born small for gestational age (SGA) who were participating in a randomized, double-blind, dose-response trial. Patients were randomly and blindly assigned to treatment with either 3 IU (group A) or 6 IU (group B) GH/m(2).d ( approximately 0.033 or 0.067 mg/kg.d, respectively). The mean (+/-SD) birth length was -3.6 (1.4), the age at the start of the study was 8.1 (1.9) yr, and the height SD score (SDS) at the start of the study -3.0 (0.7). Seventeen of the 54 children were partially GH deficient (stimulated GH peak, 10-20 mU/liter). Fifteen non-GH-treated, non-GH-deficient, short children born SGA, with similar inclusion criteria, served as controls [mean (+/-SD) birth length, -3.3 (1.2); age at start, 7.8 (1.7) yr; height SDS at start, -2.6 (0.5)]. GH treatment resulted in an AH above -2 SDS in 85% of the children after a mean (+/-SD) GH treatment period of 7.8 (1.7) yr. The mean (SD) AH SDS was -1.1 (0.7) for group A and -0.9 (0.8) for group B, resulting from a mean (+/-SD) gain in height SDS of 1.8 (0.7) for group A and 2.1 (0.8) for group B. No significant differences between groups A and B were found for AH SDS (mean difference, 0.3 SDS; 95% confidence interval, -0.2, 0.6; P > 0.2) and gain in height SDS (mean difference, 0.3 SDS; 95% confidence interval, -0.1, 0.7; P > 0.1). When corrected for target height, the mean corrected AH SDS was -0.2 (0.8) for group A and -0.4 (0.9) for group B. The mean (+/-SD) AH SDS of the control group [-2.3 (0.7)] was significantly lower than that of the GH-treated group (P < 0.001). Multiple regression analysis indicated the following predictive variables for AH SDS: target height SDS, height SDS, and chronological age minus bone age (years) at the start of the study. GH dose had no significant effect. In conclusion, long-term continuous GH treatment in short children born SGA without signs of persistent catch-up growth leads to a normalization of AH, even with a GH dose of 3 IU/m(2).d ( approximately 0.033 mg/kg.d)

Environmental aspects of tensile membrane enclosed spaces

Buildings enclosed by fabric membranes are very sensitive to changes in environmental conditions as a result of their low mass and low thermal insulation values. Development in material technology and the understanding of the structural behaviour of tensile membrane structures along with the vast progress in computer formfinding software, has made it possible for structural design of tensile membrane structures to be approached with almost total confidence. On the contrary, understanding of the environmental behaviour in the spaces enclosed by fabric membrane and their thermal performance is still in its infancy, which to some extent has hindered their wide acceptance by the building industry. The environmental behaviour of tensile membrane structures is outlined and the possible use of the fabric’s topology and geometry particularly to enhance ventilation rates and airflow velocities within the enclosed space is discussed. A need for further research in this area is identified in order to fully realise the potential benefits offered by these structures

Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial

The growth-promoting effect of continuous GH treatment was evaluated over 5 yr in 79 children with short stature (height SD score, less than -1.88) born small for gestational age (SGA; birth length SD score, less than -1.88). Patients were randomly and blindly assigned to 1 of 2 GH dosage groups (3 vs. 6 IU/m2 body surface-day). GH deficiency was not an exclusion criterium. After 5 yr of GH treatment almost every child had reached a height well within the normal range for healthy Dutch children and in the range of their target height SD score. Only in children who remained prepubertal during the study period was the 5-yr increase in height SD score (HSDS) for chronological age significantly higher in the study group receiving 6 compared to 3 IU GH/m2 x day. Remarkably, the 5-yr increment in HSDS for chronological age was not related to spontaneous GH secretion, maximum GH levels after provocation, or baseline insulin-like growth factor I levels. GH treatment was associated with an acceleration of bone maturation regardless of the GH dose given. The HSDS for bone age and predicted adult height increased significantly. GH treatment was well tolerated. In conclusion, our 5-yr data show that long term continuous GH treatment at a dose of 3 or 6 IU/m2 x day in short children born SGA results in a normalization of height during childhood followed by growth along the target height percentile

Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens

Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age. Girls were randomly assigned to group A (4 IU/m(2).d; approximately 0.045 mg/kg/d), group B (first year, 4 IU/m(2).d; thereafter 6 IU/m(2).d), or group C (first year, 4 IU/m(2).d; second year, 6 IU/m(2).d; thereafter, 8 IU/m(2).d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 +/- 0.7 yr, low dose micronized 17beta-estradiol was given orally. After a mean duration of GH treatment of 8.6 +/- 1.9 yr, FH was reached at a mean age of 15.8 +/- 0.9 yr. FH, expressed in centimeters or SD score, was 157.6 +/- 6.5 or -1.6 +/- 1.0 in group A, 162.9 +/- 6.1 or -0.7 +/- 1.0 in group B, and 163.6 +/- 6.0 or -0.6 +/- 1.0 in group C. The difference in FH in centimeters, corrected for height SD score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, -1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH SD score, more than -2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH SD score: GH dose, height SD score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated. In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year HV

Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial

textabstractThe growth-promoting effect of continuous GH treatment was evaluated over 5 yr in 79 children with short stature (height SD score, less than -1.88) born small for gestational age (SGA; birth length SD score, less than -1.88). Patients were randomly and blindly assigned to 1 of 2 GH dosage groups (3 vs. 6 IU/m2 body surface-day). GH deficiency was not an exclusion criterium. After 5 yr of GH treatment almost every child had reached a height well within the normal range for healthy Dutch children and in the range of their target height SD score. Only in children who remained prepubertal during the study period was the 5-yr increase in height SD score (HSDS) for chronological age significantly higher in the study group receiving 6 compared to 3 IU GH/m2 x day. Remarkably, the 5-yr increment in HSDS for chronological age was not related to spontaneous GH secretion, maximum GH levels after provocation, or baseline insulin-like growth factor I levels. GH treatment was associated with an acceleration of bone maturation regardless of the GH dose given. The HSDS for bone age and predicted adult height increased significantly. GH treatment was well tolerated. In conclusion, our 5-yr data show that long term continuous GH treatment at a dose of 3 or 6 IU/m2 x day in short children born SGA results in a normalization of height during childhood followed by growth along the target height percentile

Seasonality of diagnosis of type 1 diabetes mellitus in the Netherlands (Young Dudes-2)

Background: The aim of this study was to investigate seasonality in the initial presentation of type 1 diabetes mellitus (T1DM) among Dutch children. Methods: Observational, nationwide study in the Netherlands. Using the national registry for both healthcare reimbursement and pharmaceutical care, data of all Dutch children (aged 0-14 years) with a diagnosis of T1DM in the period 2009-2011 were obtained. Results: During the study period (2009-2011) an average annual number of 2.909.537 children aged 0-14 lived in the Netherlands and 676 children were diagnosed with T1DM per year, translating into an annual incidence rate (IR) of T1DM of 23.2 per hundred thousand children (ptc). The annual IR differed significantly (p = 0.03) between seasons: 6.4 ptc in winter, 4.9 ptc in spring, 5.4 ptc in summer and 6.6 ptc in autumn. This pattern was present within both boys and girls Conclusions: Among Dutch children aged 0-14 years, there is seasonality in the of T1DM with a peak incidence in autumn and winter

Long-term effects of growth hormone (GH) treatment on body composition and bone mineral density in short children born small-for-gestational-age:six-year follow-up of a randomized controlled GH trial

Context Alterations in the GH-IGF-I axis in short small-for-gestational-age (SGA) children might be associated with abnormalities in bone mineral density (BMD) and body composition. In addition, birth weight has been inversely associated with diabetes and cardiovascular disease in adult life. Data on detailed body composition in short SGA children and long-term effects of GH treatment are very scarce. Objective To investigate effects of long-term GH treatment on body composition and BMD by dual energy X-ray absorptiometry (DXA) in short SGA children. Design Longitudinal 6-year GH study with a randomized controlled part for 3 years. Results At baseline, fat percentage standard deviation score (SDS) and lumbar spine BMD SDS corrected for height (BMAD(LS) SDS) were significantly lower than zero. Lean body mass (LBM) SDS adjusted for age was also reduced, but LBM adjusted for height (LBM SDSheight) was not decreased. GH treatment induced a decrease in fat percentage SDS and an increase in BMAD(LS) SDS. LBM SDSheight remained similar in GH-treated children, but deteriorated in untreated controls. When these untreated controls subsequently started GH treatment, their LBM SDSheight rapidly normalized to values comparable with zero. Conclusion During long-term GH treatment in short SGA children, fat percentage SDS decreased and BMAD(LS) SDS increased. These effects of GH treatment were most prominent in children who started treatment at a younger age and in those with greater height gain during GH treatment. LBM SDSheight remained around 0 SDS in GH-treated children, but declined to low normal values in untreated controls