RESUMEN
In children and adolescents, markers of bone and collagen metabolism reflect the dynamics of skeletal growth and development. Treatment with recombinant human growth hormone [rhGH] has a marked effect on bone formation and resorption. This bone remodeling is well reflected on specific markers that can be measured in blood and urine. The aim of this study was to assess the potential role of bone remodeling markers in the assessment of the response to rhGH in GHD children. The study included 35 children and adolescents, 20 of which had GHD [14 boys and 6 girls], with a mean age of 14.46 +/- 2.47 years and 15 controls [8 boys and 7 girls], 11.3 +/- 2.01 years old, Anthropometric measurements were performed, and blood and morning urine samples were collected for estimation of total serum calcium, inorganic phosphorus, total ALP, OC and urinary DPD. DPD values were corrected to urinary creatinine concentrations and expressed as deoxypyridinoline/creatinine [DPD/cr] ratio. Patients started rhGH therapy, laboratory assays were repeated after 3 months, and anthropometric measurements were repeated at 3-monthly intervals for one full year. Bone turnover markers [calcium, phosphate, ALP, OC, and urinary DPD] were measured before and after 3 months of onset of rhGH. The results showed that in all patients, rhGH evoked continuous improvements in height standard deviation scores [SDS], with no significant effect on weight SDS. Height velocity SDS [HVSDS] was high during the first 3 months of rhGH, decreased thereafter, supporting the waning of rhGH, Pre-treatment Level of the ALP and OC were lower in patients than controls. Differences in serum OC levels between patients and controls were high enough to discriminate between the two groups [p<0.0001]. Both increased substantially after rhGH, Basal and after 3 months value of ALP, OC and DPDlcr ratio was 106.95 +/- 32.76 and 144.75 +/- 38.20 IUIL; 6.80 +/- /- 3.74 and 31.78 +/- 26.12 nglml; 23.69 +/- 22.49 and 37.75 +/- 29.28; with p=0.008, p=0.0001 and p>0.05, respectively. There was a significant positive correlation between the both serum ALP basal and after 3 months and overall 1st year HVSDS [r=0.69, p=0.019, p=0.86, p=0.001, respectively]. There was a significant positive correlation between serum levels of OC and urinary DPDlcr ratio in both, patients before rhGH [r=0.538, p=0.014] and controls [r=0.654, p=0.008]. Basal values of DPD/cr were positively correlated with HVSDS after 3 months [r=0.48, p0.034] and after 3 months of rhGH DPD/cr were positively correlated with height SDS [r=0.46, p=0.04]
Conclusion: bone formation markers, namely ALP and OC and bone resorption markers, namely DPD increase during growth hormone [GH] therapy. At least, one full year of observation is mandatory to detect the impact of rhGH on height measurements, while bone-remodeling markers may be used as early predictors of the long-term response to the expensive rhGH in a child with GHD. OC measurement may be used as an adjuvant assay, together with height measurements and GH stimulation tests, in the initial diagnosis of GHD as it could differentiate between patients and controls
RESUMEN
The objective of this study is to compare glycemic control and safety of fast-acting insulin as the mealtime insulin instead of regular human insulin. This was a 9 months study that enrolled 16 pediatric patients [8 males and 8 females], age 9.1 +/- 6.5 years, with type 1 diabetes of a mean duration of 20.6 +/- 10.4 months. Patients were switched from regular insulin to a fast-acting insulin analog as the mealtime insulin. Intermediate-acting insulin remained unchanged and was taken as a morning and an evening dose. A 7-point blood glucose profile, HbA1c, frequency of hypoglycemic attacks and total daily insulin requirements were registered and analyzed in all 16 patients. All data were evaluated for the 3 months before the change, 3 and 6 months afterwards. The results showed that glycated hemoglobin, mean blood glucose and mean postprandial blood glucose were significantly lower 6 months after treatment with fast-acting insulin analog when compared to values before the start of the study [mean HbA1c 7.5 +/- 0. 7% versus 8.7 +/- 0.9, mean blood glucose 129.3 +/- 12.5mg/dl versus 168.1 +/- 17.7 and mean postprandial blood glucose 159.9 +/- 20.4mg/dl versus 200.3 mg/dl +/- 17.3] [p<0.0001]. Prelunch and predinner blood glucose were significantly lower after 6m of treatment with fast-acting insulin analog [119.1 +/- 21.1mg/dl versus 139.2 +/- 26.6, 122.3 +/- 20.4mg/dl versus 156.6 +/- 31. 7] [p=0.01]. However, dawn and pre-breakfast blood glucose did not differ significantly from the values on regular insulin [127.1 +/- 27 versus 113.7 +/- 16.3, 152.9 +/- 30.9 versus 127.9 +/- 26.6 mg/dl, respectively] [p>0.05]. Body mass index [BMI], total insulin dose and mealtime insulin to basal ratio showed no statistically different change after 6 months of fast-acting insulin analog. The overall rate of hypoglycemic events, whether major or minor was significantly lowered [28.5 +/- 22.4 versus 18.8 +/- 5.02] [p= 0.0001] after 6 months of fast-acting insulin analog
Conclusion: Insulin aspart provides better glycemic control and stability with no increase in BMI after 6 months of treatment, when compared with regular insulin. This improvement was accompanied by a decrease in the frequency of hypoglycemic episodes
RESUMEN
The objective of this study is to evaluate the role of IGF-I and IGFBP-3 in fetal macrosomia in diabetic and non-diabetic pregnancies. This study is a cross-sectional estimation of IGF-I and IGFBP3 in infants of diabetic mothers [IDM], macrosomic and average weight infants of non-diabetic mothers. Cord blood of 23 IDM delivered by caesarian section [CS] and 20 control infants of healthy non-diabetic mothers was collected and levels of IGF-I and IGFBP-3 estimated. Patients and controls were subdivided into 2 groups according to the birth weight [AGA and LGA]. The level of serum IGF-i and IGFBP-3 was correlated in each group to fetal weight, length, head circumference [HC], mid-arm circumference [MAC], ponderal index [PI] and placental weight. The results proved that the level of IGF-I was significantly higher in IDM [mean 218.5 ng/mL +/- 32.5] than in the controls [mean 153.1 ng/mL +/- 52.6] [p=0.0001]. IGF-I was significantly positively correlated to weight SDS [r=0. 665, p<0. 001], length SDS [r=0.54, p=0. 008], HC SDS [r=0.49, p=0.017], MAC [r=0.67, p=0.0001], ponderal index [PI] [r=0.636, p=0. 001] and placental weight [r=0.605, p=0.02] in IDM as well as in the control [r=0.67, p=0.001; r=0.725, p=0.0001; r=0.606, p=0.005; r=0.63, p=0.003; r=0.6, p=0.003; r=0.88, p<0.001, respectively]. The level of IGFBP-3 was significantly higher in IDM [mean 5.1 ng/mL +/- 1.5] than in the controls [mean 2.8 ng/mL +/- 1.1] [p=0.0001]. There was a significant correlation of IGF-I to IGFBP-3 level present in controls [r=0.527, p<0.001] unlike in IDM where no significant correlation could be detected. IGFBP-3 was significantly correlated to weight SDS [r=0.545, p=0.013] and length SDS [r=0.616, p=0.004], MAC [r=0.52, p=0.018] and placental weight [t=0.658, p= 0.002] in controls, while it was not correlated to anthropometric parameters except for a mild correlation to length SDS [r=0.43, p=0.036] in IDM. Also it was not correlated to placental weight in IDMs. The significant correlation of IGF-I level to IGFBP-3 present in controls [r=0.527, p<0.001], could not be found in IDM [r=0.38, p>0.05]
Conclusion: IGFs and their binding proteins are major regulators of fetal growth. Macrosomia of diabetic pregnancies is associated with a high level of IGF-I and IGFBP-3 in fetal blood. Placental weight parallels fetal size proving that there are IGF-I receptors in the placenta. IGF-I and IGFBP-3 appears to be an in utero growth promoter in the development of fetal macrosomia also in infants of non-diabetic women. The dissociation of the IGF-I from the IGFBP-3 suggests that other factors influence the regulation IGFs and fetal growth in diabetes mellitus