Exercise training improves physical fitness and vascular function in children with type 1 diabetes.

Children with type 1 diabetes mellitus (DM1) show endothelial dysfunction and mild artery wall thickening compared to their age-matched healthy peers. In this study, we examined the effect of 18-week exercise training on physical fitness and vascular function and structure in children with DM1. We examined physical fitness, brachial artery endothelial function [flow-mediated dilation (FMD)], common carotid artery diameter, wall thickness and wall-to-lumen ratio before and after 18-week exercise training in children with DM1 (n = 7). Physical fitness, measured as maximal oxygen consumption, improved after training (p = 0.039). Brachial artery FMD improved from 7.5 ± 4.2 to 12.4 ± 5.2 (p = 0.038). Carotid artery diameter, wall thickness and wall-to-lumen ratio did not change significantly (p = 0.26, 0.53 and 0.27, respectively). We showed that exercise training in children with DM1 effectively reverses endothelial dysfunction and improves physical fitness. These data emphasize the important role for physical activity in the management of DM1.

Sulphonylurea therapy improves cognition in a patient with the V59M KCNJ11 mutation.

BACKGROUND: KCNJ11 mutations are a common cause of diabetes diagnosed in the first 6 months of life, and approximately 25% of patients have neurological features. Sulphonylureas have been shown to improve glycaemic control and also motor function, but the impact on cognitive function has not been extensively addressed previously. METHODS: The patient had a low birth weight and was found to have diabetes at the age of 2 days. The patient was treated with insulin from diagnosis. The child also had marked developmental delay so that his average functional age was 2.5 years when he was 12 years old. A V59M mutation in KCNJ11 was found on sequencing, resulting in a diagnosis of intermediate developmental delay, epilepsy, neonatal diabetes (DEND) syndrome. Identification of a Kir6.2 mutation allowed insulin injections to be replaced by glibenclamide tablets. RESULTS: This resulted not only in improved glycaemic control (HbA(1c) fell from 8.1 to 6.5%), but also an impressive improvement in many aspects of cognitive function, with the functional age increasing to 4 years within 6 months of treatment change. CONCLUSIONS: This is the first clear report of cognitive function improving in a patient with the neurological features associated with a K(ATP) channel mutation following transfer to sulphonylureas. The finding of cognitive improvement suggests that glibenclamide is likely to be acting directly on the brain and not just on nerve and muscle, improving muscle strength.

High prevalence of testicular adrenal rest tumors, impaired spermatogenesis, and Leydig cell failure in adolescent and adult males with congenital adrenal hyperplasia.

In male patients with congenital adrenal hyperplasia, testicular tumors, or so-called adrenal rest tumors, have been described, but their presence in well controlled patients is thought to be rare. In this study, the prevalence of testicular tumors in 17 adolescent and adult male patients with congenital adrenal hyperplasia (age, 16-40 yr) was investigated. In 16 of 17 patients, one or more testicular tumors, ranging in maximal length from 0.2-4.0 cm, were found on ultrasonography. In 6 patients, the testicular tumors were palpable. Undertreatment, defined as the presence of a salivary androstenedione level (mean of 6 saliva samples collected over 24 h with intervals of 4 h) above the upper reference morning level, was found in 5 of 17 patients at the time of investigation. The other 12 patients were treated adequately or even over treated at the time of investigation. Nevertheless, 11 of these 12 patients showed testicular tumors on ultrasonography. Neither the presence of undertreatment at the time of investigation nor characteristics of the therapeutic regimen (daily dose of hydrocortisone equivalents per body surface, the use of glucocorticoid medication either two or three times a day, or the time of taking the highest glucocorticoid dose either in the morning or the evening) could predict tumor size (maximal diameter of largest tumor). In patients who were heterozygous or homozygous for the deletion or conversion of the CYP21 gene, tumor size was significantly larger than in patients who did not have this genotype. Impairment of Leydig cell function as manifested by decreased plasma levels of T was found in 6 of 17 patients. Semen analysis in 11 patients revealed azoospermia in 3 patients and poor semen quality in 4 patients. We conclude that, when carefully sought for, testicular adrenal rest tumors are frequently present in adolescent and adult males with congenital adrenal hyperplasia and are often accompanied by impaired spermatogenesis and Leydig cell failure.

Newborn screening for congenital adrenal hyperplasia in the Netherlands.

OBJECTIVE: To evaluate whether congenital adrenal hyperplasia (CAH) patients can be detected by newborn screening before the occurrence of life-threatening salt wasting and whether the prevalence, specificity, and sensitivity are adequate enough for a routine screening procedure. DESIGN: From 1998, a 2-year regional pilot screening for CAH was performed. In 1998, cutoff levels for 17OHP were primarily based on birth weight, and in 1999 on gestational age. In addition, nationwide, all newly diagnosed patients with CAH were reported to the Dutch Pediatric Surveillance Unit to compare screened CAH patients with CAH patients in the area without screening. RESULTS: In 2 years, 176 684 newborns were screened and 15 CAH patients (7 males/8 females) were detected. Therapy was started at the median age of 7 days. In the area without screening, 223 307 infants were born and 19 CAH patients (10 males/9 females) were reported to the Dutch Pediatric Surveillance Unit. Therapy was started at the median age of 14 days. The mean (standard deviation) serum sodium concentration was 134.5 (3.4) mmol/L in the area of screening versus 124.5 (10.8) mmol/L in the area without screening. The overall prevalence was 1:11 764. In 1998 and 1999, the specificity was 99.76% and 99.97%, respectively. The positive predictive value was 4.5% and 16%, respectively. To date, no false-negative cases have been detected. CONCLUSION: Severe salt wasting can be prevented by neonatal screening. The prevalence, specificity, and sensitivity allowed addition of screening for CAH to the routinely performed national neonatal screening program.