William V. Tamborlane

Prospective clinical trial of human growth hormone in short children without growth hormone deficiency

Ten unselected, apparently healthy short children who were capable of normal growth hormone secretion were given human growth hormone (0.1 U/kg 1M thrice weekly) for 6 months to determine whether such treatment might lead to an increase in growth velocity. During treatment, all patients increased their growth rate (from 4.3 +/- 0.3 cm/yr to 7.4 +/- 0.5 cm/yr P less than 0.001). No adverse effects were detected. During the four-day IGF generation test, IGF I and IGF II levels rose significantly from 0.32 +/- 0.04 U/ml to 0.62 +/- 0.13 U/ml and from 279 +/- 36 ng/ml to 434 +/- 49 ng/ml, respectively. However, the growth response was not predicted by either the acute rise in IGF I or that in IGF II. Human growth hormone in standard doses may be capable of inducing accelerated growth in some short children without growth hormone deficiency. Measurements of IGF I and II cannot be used to predict which children will respond.

Longitudinal Assessment of Neuroanatomical and Cognitive Differences in Young Children with Type 1 Diabetes: Association with Hyperglycemia

Significant regional differences in gray and white matter volume and subtle cognitive differences between young diabetic and nondiabetic children have been observed. Here, we assessed whether these differences change over time and the relation with dysglycemia. Children ages 4 to <10 years with (n = 144) and without (n = 72) type 1 diabetes (T1D) had high-resolution structural MRI and comprehensive neurocognitive tests at baseline and 18 months and continuous glucose monitoring and HbA1c performed quarterly for 18 months. There were no differences in cognitive and executive function scores between groups at 18 months. However, children with diabetes had slower total gray and white matter growth than control subjects. Gray matter regions (left precuneus, right temporal, frontal, and parietal lobes and right medial-frontal cortex) showed lesser growth in diabetes, as did white matter areas (splenium of the corpus callosum, bilateral superior-parietal lobe, bilateral anterior forceps, and inferior-frontal fasciculus). These changes were associated with higher cumulative hyperglycemia and glucose variability but not with hypoglycemia. Young children with T1D have significant differences in total and regional gray and white matter growth in brain regions involved in complex sensorimotor processing and cognition compared with age-matched control subjects over 18 months, suggesting that chronic hyperglycemia may be detrimental to the developing brain.

Comparison of Glycemic Variability Associated With Insulin Glargine and Intermediate-Acting Insulin When Used as the Basal Component of Multiple Daily Injections for Adolescents With Type 1 Diabetes

OBJECTIVE—To compare the glucose variability associated with insulin glargine and NPH/Lente insulin used as the basal insulin component of a multiple daily injection (MDI) regimen in pediatric patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—Continuous glucose monitoring data were collected from a subset of patients (n = 90) who agreed to use a continuous glucose monitoring system during an active-controlled, randomized, open-label study evaluating the safety and efficacy of insulin glargine and NPH/Lente insulin used with insulin lispro as part of an MDI regimen. RESULTS—Treatment with insulin glargine resulted in significant reductions in glucose variability as measured by the SD of glucose values (adjusted mean change from baseline to week 24: −13.4 mg/dl [−0.74 mmol/l]; P ≤ 0.05), mean amplitude of glycemic excursion (−34.4 mg/dl [−1.91 mmol/l]; P ≤ 0.0001), and M value (−9.6 mg/dl [−0.53 mmol/l]; P ≤ 0.03). The corresponding reductions in glucose variability for NPH/Lente were not significant. CONCLUSIONS—Insulin glargine is associated with greater reductions in glucose variability than NPH/Lente insulin in pediatric patients with type 1 diabetes.