Efficacy of single-hormone and dual-hormone artificial pancreas during continuous and interval exercise in adult patients with type 1 diabetes: randomised controlled crossover trial

Abstract

Aims/hypothesis The aim of this study was to assess whether the dual-hormone (insulin and glucagon) artificial pancreas reduces hypoglycaemia compared with the single-hormone (insulin alone) artificial pancreas during two types of exercise. Methods An open-label randomised crossover study comparing both systems in 17 adults with type 1 diabetes (age, 37.2 ± 13.6 years; HbA 1c, 8.0 ± 1.0% [63.9 ± 10.2 mmol/mol]) during two exercise types on an ergocycle and matched for energy expenditure: continuous (60% V : O 2peak for 60 min) and interval (2 min alternating periods at 85% and 50% V : O 2peak for 40 min, with two 10 min periods at 45% V : O 2peak at the start and end of the session). Blocked randomisation (size of four) with a 1:1:1:1 allocation ratio was computer generated. The artificial pancreas was applied from 15:30 hours until 19:30 hours; exercise was started at 18:00 hours and announced 20 min earlier to the systems. The study was conducted at the Institut de recherches cliniques de Montréal. Results During single-hormone control compared with dualhormone control, exercise-induced hypoglycaemia (plasma glucose <3.3 mmol/l with symptoms or <3.0 mmol/l regardless of symptoms) was observed in four (23.5%) vs two (11.8%) interventions (p = 0.5) for continuous exercise and in six (40%) vs one (6.25%) intervention (p = 0.07) for interval exercise. For the pooled analysis (single vs dual hormone), the median (interquartile range) percentage time spent at glucose levels below 4.0 mmol/l was 11% (0.0-46.7%) vs 0% (0-0%; p = 0.0001) and at glucose levels between 4.0 and 10.0 mmol/l was 71.4% (53.2-100%) vs 100% (100-100%; p = 0.003). Higher doses of glucagon were needed during continuous (0.126 ± 0.057 mg) than during interval exercise (0.093 ± 0.068 mg) (p = 0.03), with no reported side-effects in all interventions.A. Haidar and R. Rabasa-Lhoret are joint senior authors.Electronic supplementary material The online version of this article (doi:10.1007/s00125-016-4107-0) contains peer-reviewed but unedited supplementary material, which is available to authorised users.* Rémi Rabasa-Lhoret

Dual‐hormone artificial pancreas: benefits and limitations compared with single‐hormone systems

“…Overall, less hypoglycaemia during daytime hours and exercise was observed with the dual‐hormone artificial pancreas than with a single‐hormone system ; however, results for hypoglycaemia in the overnight period were inconsistent , and the benefits of a dual‐hormone system in reducing mean glucose, for glycaemic control during the prandial period, and for preventing severe hypoglycaemia are unclear.…”

“…An early study of the addition of glucagon to closed‐loop insulin delivery also showed that fewer participants required carbohydrate for treatment of hypoglycaemia in the glucagon group (mean of 1.1 compared with 3.9 treatments per day for dual‐ vs single‐hormone) , and in a three‐way comparison of free‐living adults with Type 1 diabetes performed over 60 h more carbohydrate ingestion for treatment or prevention of hypoglycaemia was observed with both a sensor‐augmented pump (mean of 164 g) and a single‐hormone system (mean of 101 g) than with a dual‐hormone artificial pancreas (mean of 56 g) . Furthermore, in a randomized trial comparing a single‐ and a dual‐hormone system in exercising adults less carbohydrate consumption was observed with the dual‐hormone artificial pancreas . Long‐term studies are needed to evaluate if mini‐boluses of glucagon administered to prevent hypoglycaemia in the dual‐hormone artificial pancreas effectively reduce carbohydrate ingestion and thereby affect body weight.…”

“…Both single-hormone (insulin-only) and dual-hormone (insulin and glucagon) artificial pancreas systems have been developed, and each has shown superiority to CSII for maintaining glycaemic control. Although many studies of dual-hormone systems have been performed by various groups [6,[9][10][11][12][13][14][15][16][17][18][19][20][21][22], in the present review, we focus on studies with direct comparison of single-and dual-hormone artificial pancreas systems in order to isolate the effect of additional glucagon as opposed to the benefit of a closed-loop system. The aim of the review was to compare single-and dualhormone systems, with an emphasis on the efficacy and utility of glucagon in the dual-hormone artificial pancreas.…”

Future of Automated Insulin Delivery Systems

“…Automated glucagon delivery combined with exercise announcement has been shown to reduce hypoglycemia. 57 Ideally, a system would be able to automatically detect exercise. Much work has been done to detect exercise through the use of heart rate alone 58,59 or in combination with accelerometry.…”

Low doses of dasiglucagon consistently increase plasma glucose levels from hypoglycaemia and euglycaemia in people with type 1 diabetes mellitus

“…One option for further improvement might be dual‐hormone artificial pancreas (DHAP) systems which, in addition to insulin, use glucagon to counteract the effect of excessive insulin . The administration of mini‐doses of glucagon in a DHAP system has been shown to be more effective in preventing hypoglycaemia than the suspension of insulin delivery alone, particularly in situations of rapidly decreasing glucose levels, such as late postprandial hypoglycaemia or physical activity . As currently available glucagon formulations show limited stability, daily glucagon renewal is required, making the use of DHAP systems cumbersome .…”