D Elleri, M Biagioni, J M Allen, K Kumareswaran, L Leelarathna, K Caldwell, M Nodale, M E Wilinska, A Haidar, P Calhoun, C Kollman, N C Jackson, A M Umpleby, C L Acerini, D B Dunger, R Hovorka

We evaluate safety, efficacy and glucose turnover during closed-loop with meal announcement using reduced prandial insulin boluses in adolescents with type 1 diabetes(T1D). Randomized cross-over study comparing closed-loop with standard prandial insulin boluses versus closed-loop with prandial boluses reduced by 25%. Eight adolescents with T1D [M3; age 15.9(1.5)yrs; A1C 8.9(1.6)%; mean(SD); total daily dose 0.9(0.7, 1.1)IU/kg/d; median(IQR)] studied on two 36-hour-long visits. In random order, subjects received closed-loop with either standard or reduced insulin boluses administered with main meals [(50-80 g carbohydrates(CHO)] but not with snacks (15-30gCHO). Stable-label tracer dilution methodology measured total glucose appearance (Ra_total) and glucose disposal (Rd). Time in target (70-180 mg/dl) was comparable [74(66,84)% vs 80(65,96)%, p = 0.87] and so was time above 180 mg/dl [21.8(16.3,33.5)% vs 18.0(4.1,34.2)%, p = 0.87] and below 70 mg/dl [0(0,1.5)% vs 0(0,1.8)%, p = 0.88]. Mean plasma glucose was identical during the two interventions [152(16) vs 152(17)mg/dl, reduced vs standard bolus, p = 0.98]. Hypoglycemia occurred once 1.5 h post-meal during closed-loop with standard bolus. Overall insulin delivery was lower with reduced prandial boluses [61.9(55.2,75.0) vs 72.5(63.6,80.3)IU, p = 0.01] and resulted in lower mean plasma insulin concentration [186(171,260) vs 252(198,336)pmol/l, p = 0.002]. Lower plasma insulin was also documented overnight [160(136,192) vs 191(133,252)pmol/l,p = 0.01, pooled nights]. Ra_total was similar [26.3(21.9,28.0) vs 25.4(21.0,29.2)µmol/kg/min, p = 0.19] as well as Rd [25.8(21.0,26.9) vs 25.2(21.2,28.8)µmol/kg/min, p = 0.46]. Twenty five percent reduction of prandial boluses during closed-loop maintains comparable glucose control in adolescents with T1D whilst lowering overall plasma insulin levels. It remains unclear whether closed-loop therapy with 25% reduction of prandial boluses will prevent postprandial hypoglycemia. ClinicalTrials.gov Identifier NCT01629251.