Performance of an Artificial Pancreas System for Young Children with Type 1 Diabetes.

BACKGROUND: Young children 5-8 years old with type 1 diabetes (T1D) exhibit clear needs for improved glycemic control but may be limited in their ability to safely interact with an artificial pancreas system. Our goal was to evaluate the safety and performance of an artificial pancreas (AP) system among young children with T1D. RESEARCH DESIGN AND METHODS: In a randomized, crossover trial, children with T1D age 5-8 years were enrolled to receive on separate study periods (in random order) either the UVa AP using the DiAs Control Platform software with child-resistant lock-out screens (followed as an out-patient admission) or their usual insulin pump+continuous glucose monitor (CGM) care at home. Hypoglycemic events and CGM tracings were compared between the two 68-h study periods. All analyses were adjusted for level of physical activity as tracked using Fitbit devices. RESULTS: Twelve participants (median age 7 years, n = 6 males) completed the trial. Compared to home care, the AP admission resulted in increased time with blood glucose (BG) 70-180 mg/dL (73% vs. 47%) and lower mean BG (152 mg/dL vs. 190 mg/dL), both P < 0.001 after adjustment for activity. Occurrence of hypoglycemia was similar between sessions without differences in time <70 mg/dL (AP 1.1% ± 1.1%; home 1.6% ± 1.2%). There were no adverse events during the AP or home study periods. CONCLUSIONS: Use of an AP in young children was safe and resulted in improved mean BG without increased hypoglycemia. This suggests that AP use in young children is safe and improves overall diabetes control. ClinicalTrials.gov registration number: NCT02750267.

TASK-3 channel deletion in mice recapitulates low-renin essential hypertension.

Idiopathic primary hyperaldosteronism (IHA) and low-renin essential hypertension (LREH) are common forms of hypertension, characterized by an elevated aldosterone-renin ratio and hypersensitivity to angiotensin II. They are suggested to be 2 states within a disease spectrum that progresses from LREH to IHA as the control of aldosterone production by the renin-angiotensin system is weakened. The mechanism(s) that drives this progression remains unknown. Deletion of Twik-related acid-sensitive K(+) channels (TASK) subunits, TASK-1 and TASK-3, in mice (T1T3KO) produces a model of human IHA. Here, we determine the effect of deleting only TASK-3 (T3KO) on the control of aldosterone production and blood pressure. We find that T3KO mice recapitulate key characteristics of human LREH, salt-sensitive hypertension, mild overproduction of aldosterone, decreased plasma-renin concentration with elevated aldosterone:renin ratio, hypersensitivity to endogenous and exogenous angiotensin II, and failure to suppress aldosterone production with dietary sodium loading. The relative differences in levels of aldosterone output and aldosterone:renin ratio and in autonomy of aldosterone production between T1T3KO and T3KO mice are reminiscent of differences in human hypertensive patients with LREH and IHA. Our studies establish a model of LREH and suggest that loss of TASK channel activity may be one mechanism that advances the syndrome of low renin hypertension.