Understanding the Benefits of Glucagon in the Artificial Pancreas: Randomized Crossover Trial

Abstract

We conducted a randomized crossover comparison between dual-hormone (insulin and glucagon) artificial pancreas (DAP), single-hormone (insulin) artificial pancreas (SAP) and pump therapy (CSII) in 24 patients with type 1 diabetes (adults/pediatrics 18/6, A1c 7.6±0.7%). Patients were studied 3 times in a research facility for 24 hours and ingested meals at 8 AM, 12 PM and 5 PM, conducted activities at 9 AM and 1 PM, exercised at 7:30 PM for 60 min, ingested a snack at 9 PM and stayed in the facility overnight. Over the 24 hours, both SAP and DAP increased the percentage of time spent in target range compared to CSII in a similar fashion (SAP 62%, DAP 64%, CSII 48%; P=NS for DAP vs. SAP; P<0.01 otherwise). SAP decreased the time spent below 4 mmol/L compared to CSII by 5-fold from 16.2% to 3.1% (P<0.001) while DAP reduced it by 20-fold to 0.8% (P<0.001 vs. CSII; P=0.02 vs. SAP). Overnight (11 PM to 8 AM), both SAP and DAP achieved hypoglycemia-free control compared to CSII (time below 4 mmol/L; DAP 0%, SAP 0%, CSII 5%; P=NS for DAP vs. SAP; P<0.05 otherwise). Eight participants (34%) had at least 1 nocturnal hypoglycemic event (<3.0 mmol/L) during CSII visits compared to 0 (0%) on SAP and DAP (P<0.05). We conclude that 1) SAP and DAP are both superior to CSII; 2) DAP provides additional reduction in hypoglycemia compared to SAP and 3) SAP might be sufficient for hypoglycemia-free overnight control. Tabled 1Comparisons between DAP, SAP and CSII (median [IQR] for hypoglycemia endpoints; mean ± SD otherwise) Time plasma glucose is (%) CSII P valueCSII vs. SAP SAP P valueSAP vs. DAP DAP P valueDAP vs. CSII in target‡ 48±17 0.002 62±20 0.9 64±18 0.009 overnight target‡ 42±32 0.004 68±27 0.6 69±31 0.016 <4.0 mmol/L 16 (3.5–21) <0.001 3.1 (0.4–8.0) 0.02 0.8 (0.0–3.0) <0.001 overnight <4.0 mmol/L 4.7 (0–22) 0.014 0.0 (0.0–2.5) 0.27 0.0 (0.0–0.0) 0.005 above target‡ 41±25 0.7 37±21 0.5 40±18 0.8 Above target overnight‡ 44±41 0.14 28±28 0.36 30±30 0.2 ‡Target range 4–10 mmol/L for 2 hours post-prandially and 4–8 mmol/L otherwise Endpoints calculated using plasma glucose Open table in a new tab ‡Target range 4–10 mmol/L for 2 hours post-prandially and 4–8 mmol/L otherwise Endpoints calculated using plasma glucose