Care delivery and outcomes among Belgian children and adolescents with type 1 diabetes.

UNLABELLED: We aimed to investigate care processes and outcomes among children and adolescents with type 1 diabetes treated in hospital-based multidisciplinary paediatric diabetes centres. Our retrospective cross-sectional study among 12 Belgian centres included data from 974 patients with type 1 diabetes, aged 0-18 years. Questionnaires were used to collect data on demographic and clinical characteristics, as well as process of care completion and outcomes of care in 2008. Most patients lived with both biological or adoption parents (77 %) and had at least one parent of Belgian origin (78 %). Nearly all patients (≥95 %) underwent determination of HbA(1c) and BMI. Screening for retinopathy (55 %) and microalbuminuria (73 %) was less frequent, but rates increased with age and diabetes duration. Median HbA(1c) was 61 mmol/mol (7.7 %) [interquartile range 54-68 mmol/mol (7.1-8.4 %)] and increased with age and insulin dose. HbA(1c) was higher among patients on insulin pump therapy. Median HbA(1c) significantly differed between centres [from 56 mmol/mol (7.3 %) to 66 mmol/mol (8.2 %)]. Incidence of severe hypoglycaemia was 30 per 100 patient-years. Admissions for ketoacidosis had a rate of 3.2 per 100 patient-years. Patients not living with both biological or adoption parents had higher HbA(1c) and more admissions for ketoacidosis. Parents' country of origin was not associated with processes and outcomes of care. CONCLUSION: Outcomes of care ranked well compared to other European countries, while complication screening rates were intermediate. The observed centre variation in HbA(1c) remained unexplained. Outcomes were associated with family structure, highlighting the continuing need for strategies to cope with this emerging challenge.

Final height in children with idiopathic growth hormone deficiency treated with recombinant human growth hormone: the Belgian experience.

BACKGROUND: The growth response to recombinant hGH (rhGH) treatment and final height of 61 Belgian children (32 boys) with idiopathic growth hormone deficiency (GHD) were studied. PATIENTS/METHODS: Two patient groups were compared: Group 1 with spontaneous puberty (n = 49), Group 2 with induced puberty (n = 12). The patients were treated with daily subcutaneous injections of rhGH in a dose of 0.5-0.7 IU/kg/week (0.17-0.23 mg/kg/week) from the mean +/- SD age of 11.9 +/- 3.1 years during 5.1 +/- 2.1 years. RESULTS: rhGH treatment induced a doubling of the height velocity during the first year and resulted in a normalisation of height in 53 (87%) patients. Final height was -0.7 +/- 1.1 SDS, being 170.4 +/- 7.2 cm in boys and 158.0 +/- 6.4 cm in girls. Corrected for mid-parental height, final height was 0.0 +/- 1.1 SDS. Ninety-two percent of the patients attained an adult height within the genetically determined target height range. Although height gain during puberty was smaller in the patients with induced puberty (boys: 17.1 +/- 7.0 cm vs. 27.5 +/- 6.6 cm (p < 0.005); girls: 9.6 +/- 7.4 cm vs. 22.2 +/- 6.1 cm (p < 0.005)), no differences in final height after adjustment for mid-parental height were found between patients with spontaneous or induced puberty. CONCLUSIONS: We conclude that patients with idiopathic GHD treated with rhGH administered as daily subcutaneous injections in a dose of 0.5-0.7 IU/kg/week reach their genetic growth potential, resulting in a normalisation of height in the majority of them, irrespective of spontaneous or induced puberty.

Longitudinal study of behavioral and affective patterns in girls with central precocious puberty during long-acting triptorelin therapy.

The aim of the present study was to evaluate the behavioral and affective characteristics and the changes in psychosocial functioning resulting from precocious puberty in 15 girls with central precocious puberty treated for 2 y using the GnRH agonist long-acting triptorelin, and in 5 untreated girls. After diagnosis of precocious puberty at 6.6-10.4 y of age, height, weight and pubertal development were evaluated at 3-month intervals over 2 y. Semi-structured interviews were carried out with the patient, the parents and the pediatric endocrinologists at 1, 8, 16 and 24 months after diagnosis. Standardized questionnaires (Child Behavior Checklist, Self-esteem Inventory) were administered at 1 and 24 months or 16 and 24 months, respectively. There was a mean 1.5-y delay between the observation of signs of puberty as reported by the parents and the diagnosis of precocious puberty at the first consultation of a pediatric endocrinologist. Before follow-up, all 20 girls were very concerned about physical differences from peers, particularly breast development. During therapy, breast regression to minimal or absent development occurred in 5/15 treated patients, who then no longer felt embarrassed about pubertal development in contrast to the other patients. Fear of sexuality remained obvious throughout the study in most patients. Feelings of loneliness and exemplary behavior were observed and tended to decrease in the treated patients and to increase in the untreated patients. Elevated scores of withdrawal, anxiety/depression and somatic complaints at Child Behavior Checklist were still observed after 2 y. These changes in behavioral and affective characteristics appeared to be related neither to height and weight, nor to development of pubic hair, which progressed in most patients. After 2 y, the physical differences remained a concern for 13 girls and the risk of short adult stature for 6. In summary, some behavioral and affective characteristics and particularities in psychosocial functioning are observed in girls with precocious puberty. During treatment with long acting triptorelin, problematic behavior and functioning decrease slightly, particularly in the few girls showing breast regression to minimal or absent development.

Paucity of intrahepatic bile ducts, solitary kidney and atrophic pancreas with diabetes mellitus: atypical Alagille syndrome?

UNLABELLED: A child with the tentative diagnosis of Alagille syndrome is reported. Additional renal abnormalities are unilateral kidney agenesis and a kidney with subcortical cysts with decreased function. At the age of 5 years, insulin-dependent diabetes mellitus developed, with the pancreas being atrophic and negative pancreatic islet cell antibodies. CONCLUSION: This observation extends the picture of Alagille syndrome and suggests an overlap with renal-hepatic-pancreatic dysplasia (Ivemark syndrome).

Influence of age, sex, and insulin on osteoblast function: osteoblast dysfunction in diabetes mellitus.

The osteoblast function was evaluated in normal and diabetic children and adults by measurements of the serum concentration of the carboxy-terminal extension peptide of procollagen (PICP), total and skeletal alkaline phosphatase (ALP), and osteocalcin. Moreover, the osteoblast-stimulating growth factor, insulin-like growth factor I (IGF-I), was measured in the same samples. In normal children (n = 420; age, 5-20 yr), a marked pubertal increase of serum IGF-I (peak values at age 14-16 yr in both sexes), osteocalcin, and total and skeletal ALP (peak values earlier in girls than in boys) and a small increase in PICP were observed. All osteoblast markers and IGF-I were markedly lower in normal adults (n = 229; age, 21-69 yr) than in children. All osteoblast parameters showed a high degree of correlation (P < 0.001) with each other. In adolescents (n = 104) treated for insulin-dependent diabetes mellitus (IDDM), serum IGF-I (-19%), osteocalcin (-28%), and skeletal ALP (-28%) were markedly decreased, whereas total ALP was significantly increased (29%), and serum PICP remained normal. In adult IDDM (n = 125), both serum IGF-I (-41%) and osteocalcin (-24%) were decreased, but skeletal ALP and PICP remained normal. A similar abnormality in serum IGF-I and osteocalcin was observed in white (n = 61) and Pima Indian (n = 16) non-IDDM patients. The concentration of skeletal ALP was highly significantly correlated (r > or = 0.9) with total ALP in both normal and diabetic subjects, but the slope of the regression was significantly different, indicating the presence of other, probably intestinal, ALP in all types of diabetes. In conclusion, the osteoblast function is significantly decreased in diabetic patients, which can best be characterized as a maturation defect, since the early osteoblast marker, PICP, remained normal in all types of diabetes, whereas a later marker, skeletal ALP, is frankly abnormal only in diabetic children. The most mature osteoblast marker, osteocalcin, is decreased in all types of diabetes irrespective of age.

Association of particular HLA class II alleles, haplotypes and genotypes with susceptibility to IDDM in the Belgian population.

Using a highly discriminatory DNA typing technique, based on the polymerase chain reaction and reverse dot blot hybridization, more refined results were obtained on the association of particular HLA class II alleles, haplotypes and genotypes with insulin-dependent diabetes mellitus in the Belgian population. The previously reported predisposing effect for the DRB1*0301 encoded DR3 serologic specificity was confirmed and could be assigned to the DRB3*0200 encoded DR52b serologic specificity. A second high risk haplotype, DRB1*0401-DQB1*0302 encoding the DR4-DQ8 serologic specificity, accounted for increased susceptibility both in the total insulin-dependent diabetic population and among DR4-positive patients. Moreover, we found that these DR4 associated DRB1 and DQB1 alleles act as independent risk factors. A possible role for the DPB1 locus can be rejected since the observed predisposing effect for DPB1*0202 probably occurred due to linkage disequilibrium of this allele with DRB1*0301. Particular extended haplotypes accounted for the decreased relative risk observed for the DR2, DR11 and DR13 serologic specificities. The highest relative risk was observed for those DQA1/DQB1 genotypes, allowing for the formation of 4SS (DQ alpha Arg52+/DQ beta Asp57-) heterodimers.

Serum levels of growth hormone-binding protein and insulin-like growth factor I in children and adolescents with type 1 (insulin-dependent) diabetes mellitus.

Serum levels of insulin-like growth factor I are reduced in patients with Type 1 (insulin-dependent) diabetes mellitus. To evaluate the role of the hepatic growth hormone receptor in the decreased serum concentrations of insulin-like growth factor I, serum levels of the high affinity growth hormone-binding protein, which is qualitatively and quantitatively related to the hepatic growth hormone receptor, and of insulin-like growth factor I were measured in 70 children and adolescents with Type 1 diabetes and 105 healthy control children. Analysis of variance revealed a significant negative effect of Type 1 diabetes on serum levels of the growth hormone-binding protein and of insulin-like growth factor I. In the diabetic patients, serum levels of the growth hormone-binding protein were positively related to body mass index and to insulin dose per kg body weight, and were not influenced by pubertal stage, gender, or plasma levels of haemoglobin A1c. Serum levels of insulin-like growth factor I increased during early puberty reaching peak levels at mid-puberty and decreasing thereafter. No relationship was found between serum levels of growth hormone-binding protein and of insulin-like growth factor I. Our data suggest that decreased liver somatogenic receptor levels, as reflected by the concentrations of circulating growth hormone-binding protein, play a minor role in the suppressed concentrations of circulating insulin-like growth factor I. Post-growth hormone receptor defects or changes in the insulin-like growth factor binding proteins probably contribute more to the lower serum levels of insulin-like growth factor I.

Hyperthyroidism accelerates growth in Turner's syndrome.

Graves' disease in a girl with Turner's syndrome (karyotype 46,Xdel(Xp)) is described. Hyperthyroidism led to a pronounced acceleration of height velocity. During treatment with methimazole and L-thyroxine, height velocity normalized. The patient also developed spontaneous puberty with a clear-cut pubertal growth spurt. Final height, however, did not appear to be influenced either by Graves' disease or by spontaneous puberty.

Growth hormone deficiency in a girl with the Cohen syndrome.

A girl with the Cohen syndrome and isolated growth hormone deficiency is described. Treatment with biosynthetic human growth hormone resulted in marked catch up growth to normal stature. It is concluded that growth hormone deficiency should be ruled out in patients with the Cohen syndrome and small stature.

Growth hormone deficiency: a hidden obstetrical trauma?

Fetal presentation, mode of delivery and onset of labour were reviewed in 177 patients with documented growth hormone deficiency. Non-cephalic presentations were about ten times more frequent in this group of patients than in a control population. All children with breech position were delivered vaginally and spontaneously, suggesting a pituitary insult during vaginal delivery. 'True idiopathic' isolated growth hormone deficiency was frequently found in association with induction of labour. The data indicate that even a mild birth trauma may result in growth hormone deficiency.

Sensorineural hearing loss in sporadic congenital hypothyroidism.

Hearing acuity was assessed in 45 children with sporadic congenital hypothyroidism during adequate long-term treatment. Otoscopy was performed in each and additional tympanometry in some of them. Secretory otitis media was found in 6 and was treated medically or by inserting grommets in the eardrum. In these children, hearing acuity was assessed after the otitis had been cured. Hearing acuity was measured either by conventional monoaural pure-tone audiometry (125-8000 Hz) or by binaural free field testing depending on the child's age (above and below 4 years respectively). Hearing was normal in 36 (80%) children. In the remaining 9, sensorineural hearing loss to some degree was detected affecting the higher frequencies in particular. Perceptive deafness required the use of a hearing aid in 4 children. No relationship could be found between hearing acuity and chronological age or bone age at diagnosis of congenital hypothyroidism or type of hypothyroidism. Sensorineural hearing loss is common in children with congenital hypothyroidism and should be searched for carefully and systematically to avoid difficulties related to speech and language development.