Randomized Trial of the Insulin-Only iLet Bionic Pancreas for the Treatment of Cystic Fibrosis- Related Diabetes.

OBJECTIVE: Cystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis and adds significant morbidity and treatment burden. We evaluated the safety and efficacy of automated insulin delivery with the iLet bionic pancreas (BP) in adults with CFRD in a single-center, open-label, random-order, crossover trial. RESEARCH DESIGN AND METHODS: Twenty participants with CFRD were assigned in random order to 14 days each on the BP or their usual care (UC). No restrictions were placed on diet or activity. The primary outcome was the percent time sensor-measured glucose was in target range 70-180 mg/dL (time in range [TIR]) on days 3-14 of each arm, and key secondary outcomes included mean continuous glucose monitoring (CGM) glucose and the percent time sensor-measured glucose was in hypoglycemic range <54 mg/dL. RESULTS: TIR was significantly higher in the BP arm than the UC arm (75 ± 11% vs. 62 ± 22%, P = 0.001). Mean CGM glucose was lower in the BP arm than in the UC arm (150 ± 19 vs. 171 ± 45 mg/dL, P = 0.007). There was no significant difference in percent time with sensor-measured glucose <54 mg/dL (0.27% vs. 0.36%, P = 1.0), although self-reported symptomatic hypoglycemia episodes were higher during the BP arm than the UC arm (0.7 vs. 0.4 median episodes per day, P = 0.01). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either arm. CONCLUSIONS: Adults with CFRD had improved glucose control without an increase in CGM-measured hypoglycemia with the BP compared with their UC, suggesting that this may be an important therapeutic option for this patient population.

Functions of potassium channels blocked by low micromolar 4-aminopyridine in the crayfish nervous system.

4-aminopyridine (4-AP) is a potassium channel blocker that has been used to treat patients with multiple sclerosis and Lambert-Eaton disease. The concentration of this drug in the blood of patients was estimated to be in low or submicromolar range. Animal studies have shown that 4-AP at such low concentration selectively blocks a subset of channels in Kv1 or Kv3 families. The crayfish opener neuromuscular junction and ventral superficial flexor (VSF) preparations were used to examine functions of K+ channels blocked by low concentrations of 4-AP. At opener motor axons, intracellular recordings show that 4-AP could increase action potential (AP) amplitude, duration, and after-depolarization (ADP) at 10 µM. As 4-AP concentration was increased, in twofold steps, AP amplitude did not increase further up to 5 mM. AP duration and ADP increased significantly mainly in two concentration ranges, 10-50 µM and 1-5 mM. The effects of 50 µM 4-AP on the VSF were less consistent than that observed at the opener motor axons. 4-AP did not change AP amplitude of motor axons recorded with an extracellular electrode and change in AP repolarizing potential was observed in ∼25% of the axons. EPSP recorded simultaneously with AP showed an increase in amplitude with 4-AP treatment only in 30% of the axon-EPSP pairs. 4-AP also increased firing frequencies of ∼50% of axons. In four animals, 4-AP "awakened" the firing of APs from an axon that was silent before the drug. The mixture of positive and negative 4-AP effects summarized above was observed in the same VSF preparations in all cases (n = 8). We propose that there is a significant diversity in the density 4-AP-sensitive potassium channels among motor axons of the VSF. Functional significance in the differences of 4-AP sensitivity of the two motor systems is discussed.