Bone turnover in neonates: changes of urinary excretion rate of collagen type I cross-linked peptides during the first days of life and influence of gestational age.

New markers have been used to monitor the changes of bone turnover occurring during growth. Data on bone turnover rate during the perinatal period are, however, very scarce. In the present study we evaluated bone turnover rate, assessed by the measurement of urinary N-terminal telopeptide of type I collagen (NTx) concentrations, at different gestational ages, and we documented the trend of bone turnover rate occurring in the first days after birth. Urine samples were obtained from 83 healthy full term newborn infants, 16 preterm, and 17 infants of diabetic mothers (IDMs). The first miction after birth was collected. Urine samples were also collected 24 and 48 h after birth. NTx was measured by an enzyme-linked immunosorbent assay (Osteomark, Ostex International, Inc. Seattle, WA). The relationship between NTx at birth and all the other variables has been evaluated using multiple regression analysis. The changes of NTx excretion over time and the effect of the groups were studied by multivariate analysis of variance (MANOVA) for repeated measures. We found a remarkable association between gestational age and NTx concentrations at birth (R = 0.56; p < 0.00001). NTx concentrations showed a progressive decrement, reaching a nadir between the 38th and the 42nd week of gestation. The NTx concentrations changed significantly during the first 48 h of life in the three groups. Moreover, preterm infants had NTx excretion values at birth significantly higher than full term infants (p < 0.001), whereas NTx excretion rates of IDMs were not different from those of the other two groups of subjects. In conclusion, gestational age seems to be the major determinant of bone turnover in neonates; NTx excretion rate is higher before term, it slows in proximity of delivery, and it increases significantly during the first 48 h of life. Preterm infants have higher bone turnover rate than full term infants. NTx excretion rate of IDMs was comparable with those of the control subjects.

Bone modeling indexes at onset and during the first year of follow-Up in insulin-dependent diabetic children.

Osteopenia has been described as a complication of insulin-dependent diabetes mellitus (IDDM). We measured bone modeling indexes during the first year of IDDM. At each time point the values obtained from diabetic children have been compared with those of control subjects. We selected 27 prepubertal children with IDDM (6.35 +/- 2.16 years). We also enrolled 30 healthy prepubertal children of comparable age (5.85 +/- 3.05 years). Height, height standard deviation scores, glycated haemoglobin (HbA1C), basal c-peptide concentrations, insulin dose, serum concentrations of procollagen type I C-terminal propeptide (PICP), and collagen type I C-terminal telopeptide (ICTP) were measured at onset of IDDM and at 3, 6 and 12 months. ICTP was in the normal range at onset of IDDM and decreased during the follow-up to reach a significant difference compared to controls after 3, 6 and 12 months of insulin treatment (P < 0.04). PICP concentrations increased significantly at 3 months (P = 0.05) compared to onset. At 3 and 12 months PICP values were significantly higher than those of control children (P = 0.04). Correlations were found between PICP concentrations and HbA1C and c-peptide at onset of diabetes (r = -0.45 and r = 0.47, respectively). Bone formation at onset of IDDM is not impaired; the introduction of insulin therapy, together with the achievement of a good metabolic control, determines an increase of bone matrix formation coupled with a decrease of bone resorption, that determines a positive balance of bone modeling.

[Metabolic control in insulin dependent diabetic adolescent during a trial by computerized graphic meter for the assessment of glycemia]. / Controllo metabolico in giovani diabetici durante l'utilizzo di un videoreflettometro computerizzato per la determinazione della glicemia.

Insulin-dependent diabetes mellitus is associated to important micro and macro vascular complications. A good metabolic control can reduce the risk of complications. Aim of the study was to evaluate the metabolic control in adolescent diabetic patients using an educational system with graphic visualisation of capillary glycaemia. 40 (22 males, 18 females) insulin-dependent diabetic patients (age: 16.9 +/- 3.5 yrs; duration of diabetes: 6.7 +/- 4.6 yrs) were divided in two groups matched for age, sex, duration of diabetes and metabolic control. Patients of group 1 used One Touch II Video for three months. One Touch II Video is an educational program for diabetes mellitus linked to a meter for glycaemia assessment. Patients of group 2 were used as control group. All data were expressed as a mean +/- SD and were analysed by parametric t-Student test. In group 1 HbA1c at the end of the study was significantly reduced compared to the initial value: 8.58 +/- 1.65% vs 7.9 +/- 1.0% (p < 0.05). In group 2 HbA1c at end of the study was no different from the initial value. At short term One Touch II Video could be a useful instrument to improve metabolic control in insulin-dependent diabetic adolescents.

Human growth hormone treatment in prepubertal children with achondroplasia.

We studied the effects of recombinant human growth hormone (GH) treatment in 6 prepubertal children with achondroplasia. The patients' age ranged from 2 11/12 to 8 5/12 years and the GH dose was of 0.1 IU/kg/day subcutaneously. Auxological assessments and bone age determinations were performed 6 months before, at the beginning, and after 6 and 12 months of therapy. The growth velocity increase during the whole year of treatment ranged from 1.1 to 2.6 cm/year in 3 patients while in the others no variation was detected. No side effects were observed during the trial apart from a slight advancement of bone age in two patients. MRI at the cervicomedullary junction and CT scan of the base of the skull did not show any variation of the dimensions of the foramen magnum at the end of the trial compared to baseline. Our study shows that r-hGH can safely increase short-term growth velocity in some but not all prepubertal children with achondroplasia. Our data confirm the individual variability in the response to the GH treatment.

Urinary growth hormone excretion in children and adolescents with insulin-dependent diabetes mellitus.

Urinary growth hormone (uGH) excretion was evaluated in 96 type-1 insulin-dependent diabetic patients and 37 age-matched healthy subjects. The growth hormone concentration was measured by a solid-phase immunoradiometric assay on 3 consecutive overnight urine collections. uGH excretion was comparable between diabetic patients and healthy subjects: 10.9 (0.1-34.8) vs. 9.1 (2.6-34.5) pg/min. In both groups uGH excretion was lower in prepubertal than in pubescent or pubertal individuals (diabetic patients, H = 29.7, p = 0.001; healthy subjects, H = 10.4, p = 0.006). In diabetic patients uGH excretion was related to beta 2-microglobulin excretion (r = 0.308; p = 0.005) and to urinary albumin excretion (r = 0.230; p = 0.02) but it was independent of HbA1c and overnight glycemic values. The coefficient of variation of uGH excretion was higher in diabetic patients with respect to healthy subjects: 50 (3-141) vs. 28(3-100)% (p = 0.002). Among diabetic patients it was greater in prepubertal than in pubescent or pubertal patients (H = 13.7; p = 0.002); in contrast, it was independent of pubertal stage in healthy individuals (H = 2.4; NS). The coefficient of variation of uGH was not related to HbA1c, the duration of diabetes, the coefficient of variation of urinary albumin excretion and the coefficient of variation of beta 2-microglobulin excretion. In conclusion uGH excretion is comparable among diabetic patients and healthy subjects, but its day-to-day fluctuation is greater in the former than in the latter group. Renal function but not metabolic control can influence uGH excretion. The day-to-day fluctuation in uGH excretion is independent of metabolic control and renal function.

Prednisone treatment in newly diagnosed type I diabetic children: 1-yr follow-up.

Thirty-one children suffering from type I diabetes mellitus were arranged at onset of the disease in two different groups. Group 1 was treated with oral prednisone (60 mg X m-2 X day-1 for 14 days, 30 and 15 mg X m-2 X day-1 for 7 days). Group 2 matched the control group. All patients were treated with continuous subcutaneous insulin infusion for the first 15 days of treatment, and then with two daily injections of a mixture of intermediate- and fast-acting insulin. All subjects were followed for 1 yr. Group 1 required more insulin than group 2 after 30 days (1.5 +/- 0.3 vs. 0.6 $ 0.2 U X kg-1 X day-1, P less than .001) and after 60 days (0.8 +/- 0.1 vs. 0.5 +/- 0.06 U X kg-1 X day-1, P less than .001). After 3 mo, both groups reached the lowest mean stable HbA1 level (8.4 +/- 0.4 and 8.3 +/- 0.4% group 1 and 2 respectively). Between the 2nd and 9th mo of follow-up, mean postbreakfast C-peptide concentration increased in both groups. The highest levels of fasting C-peptide were reached by group 1 after 90 days (0.77 +/- 0.32 nM) and group 2 after 60 days (0.34 +/- 0.09 nM). The largest partial remission (C-peptide 0.3 nM, insulin requirement less than 0.5 U X kg-1 X day-1 and no glycosuria) was observed in group 1 after 180 days (5 of 16 patients) and in group 2 after 60 days (5 of 15 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

C-peptide response to arginine stimulation in diabetic children.

The extent and the clinical significance of residual beta cell function has been evaluated by radioimmunoassay of C-peptide in 41 diabetic children in different stages of evolution, using an arginine tolerance test. In control subjects a significant rise of C-peptide levels occurred after the infusion with arginine. In patients at the onset of the disease and in patients not in the remission stage, C-peptide levels showed no increment and basal values were significantly lower than in healthy control children. Children during the remission phase showed basal and peak values not significantly different from controls. A positive correlation was found between highest CPR levels compared to basal CPR values and to the age at onset of diabetes; a negative correlation was found between the duration of the disease and insulin requirement.