Feasibility of Closed-Loop Insulin Delivery in Type 2 Diabetes: A Randomized Controlled Study

Abstract

OBJECTIVEClosed-loop insulin delivery offers a promising treatment option, but to date, it has only been evaluated in type 1 diabetes. Our aim was to evaluate the feasibility of fully closed-loop subcutaneous insulin delivery in insulin-naïve patients with type 2 diabetes. RESEARCH DESIGN AND METHODSTwelve subjects (seven males, age 57.2 years, BMI 30.5 kg/m 2 ) with noninsulintreated type 2 diabetes (HbA 1c 8.4% [68 mmol/mol], diabetes duration 7.6 years) underwent two 24-h visits (closed-loop and control) in a randomized crossover design. During closed-loop visits, the subjects' routine diabetes therapy was replaced with model predictive control algorithm-driven subcutaneous insulin pump delivery based on real-time continuous glucose monitoring. Meals were unannounced, and no additional insulin was administered for carbohydrates consumed. During control visits, the usual diabetes regimen was continued (metformin 92%, sulfonylureas 58%, dipeptidyl peptidase-4 inhibitors 33%). On both visits, subjects consumed matched 50-to 80-g carbohydrate meals and optional 15-g carbohydrate snacks and remained largely sedentary. Plasma glucose measurements evaluated closed-loop performance. RESULTSCompared with conventional therapy, 24 h of closed-loop insulin delivery increased overall the median time in target plasma glucose (3.9-8.0 mmol/L) from 24 to 40% (P = 0.016), despite sensor under-reading by a median of 1.2 mmol/L. The benefit of the closed-loop system was more prominent overnight, with greater time in target glucose (median 78 vs. 35%; P = 0.041) and less time in hyperglycemia (22 vs. 65%; P = 0.041). There was no hypoglycemia during either intervention. CONCLUSIONSA closed-loop system without meal announcement and using subcutaneous insulin delivery in insulin-naïve patients with type 2 diabetes appears feasible and safe. Improvement in postprandial glucose control may require further optimization of system performance.

Closed-Loop System in the Management of Diabetes: Past, Present, and Future

“…The semiautomated CL also had been investigated in pregnant patients with T1DM and patients with T2DM with promising results. 70,71 Dassau et al 72 carried out a fully automated CL study in subjects with T1DM and found that fully automated CL is feasible and able to keep near-normal blood glucose levels for an average of 70% of the time.…”

Pharmacokinetics of insulin lispro in type 2 diabetes during closed-loop insulin delivery

“…Insulin-naïve subjects with T2D underwent investigations of closed-loop insulin delivery at the Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital, Cambridge [16]. The study was approved by the Cambridge Research Ethics Committee and subjects signed informed consent prior to the commencement of the study.…”

“…The study was approved by the Cambridge Research Ethics Committee and subjects signed informed consent prior to the commencement of the study. We analyzed data collected during a 24-h study visit when subjects' usual diabetes treatment (non-insulin glucose-lowering medication) was withheld and was replaced by exogenous insulin [16]. A subcutaneous cannula was inserted in the abdomen for the delivery of insulin lispro (Humalog, Eli Lilly, Indiana) by a study pump (Animas 2020 Johnson&Johnson, NJ) in the morning of the study.…”

“…Clinical trials have demonstrated the safety and efficacy of closed-loop delivery in adults [3], adolescents [4] and pregnant women [5] with type 1 diabetes (T1D). A recent study evaluated closed-loop system in 12 subjects with type 2 diabetes (T2D) [6] in preparation for testing in non-critically ill inpatients with insulin treated T2D [7].…”

“…In the present work, we used compartmental modelling to describe absorption of insulin lispro in subjects with T2D who underwent investigations of closed-loop insulin delivery over 24 h [16]. Model parameters were estimated using Bayesian inference [17] by fitting the statistical model to the plasma insulin concentration.…”