Hypoglycemia does not change the threshold for arousal from sleep in adolescents with type 1 diabetes.

BACKGROUND: Nocturnal hypoglycemia is a significant problem for children and adolescents with type 1 diabetes. The counterregulatory hormone response to hypoglycemia is blunted in both patients with type 1 diabetes and healthy subjects during sleep. It is not known whether the threshold for arousal from sleep is also modified by hypoglycemia. To address this question we compared the acoustic arousal threshold from sleep during hypoglycemia and euglycemia in adolescents with type 1 diabetes. METHODS: Adolescents with type 1 diabetes were studied on two occasions: under hypoglycemic and euglycemic conditions. During the hypoglycemia night, subjects underwent a hyperinsulinemic hypoglycemic clamp with nadir glucose level of 2.8 mmol/L. Hypoglycemia was initiated during stage 2 sleep and maintained during slow-wave sleep. During the euglycemia night, blood glucose was maintained at 5.5 mmol/L using the same clamp technique. The acoustic arousal threshold was determined during the first cycle of slow-wave sleep. RESULTS: Seven subjects (mean±SE, 14.2±0.8 years old, mean glycosylated hemoglobin 8.1±0.3%, duration of diagnosis 2.5±0.5 years) completed both study nights. Arousal was only noted during acoustic testing and did not occur during hypoglycemia alone. The acoustic arousal threshold during slow-wave sleep was similar under both conditions: 79±8 dB during euglycemia and 71±6 dB (P=0.353) during hypoglycemia. CONCLUSION: In adolescents with type 1 diabetes, hypoglycemia does not impair arousal from slow-wave sleep induced by an external auditory stimulus.

Structural chromosome disruption of the NR3C2 gene causing pseudohypoaldosteronism type 1 presenting in infancy.

Type I pseudohypoaldosteronism (PHA1) is a rare form of mineralocorticoid resistance presenting in infancy with renal salt wasting and failure to thrive. Here, we present the case of a 6-week-old baby girl who presented with mild hyponatraemia and dehydration with a background of severe failure to thrive. At presentation, urinary sodium was not measurably increased, but plasma aldosterone and renin were increased, and continued to rise during the subsequent week. Despite high calorie feeds the infant weight gain and hyponatraemia did not improve until salt supplements were commenced. Subsequently, the karyotype was reported as 46,XX,inv (4)(q31.2q35). A search of the OMIM database for related genes at or near the inversion breakpoints, showed that the mineralocorticoid receptor gene (NR3C2) at 4q31.23 was a likely candidate. Further FISH analysis showed findings consistent with disruption of the NR3C2 gene by the proximal breakpoint (4q31.23) of the inversion. There was no evidence of deletion or duplication at or near the breakpoint. This is the first report of a structural chromosome disruption of the NR3C2 gene giving rise to the classical clinical manifestations of pseudohypoaldosteronism type 1 in an infant.