For patients with type 1 diabetes, closed-loop delivery systems (CLS) combining an insulin pump, a glucose sensor and a dosing algorithm allowing a dynamic hormonal infusion have been shown to improve glucose control when compared with conventional therapy. Yet, reducing glucose excursion and simplification of prandial insulin doses remain a challenge. The objective of this literature review is to examine current meal-time strategies in the context of automated delivery systems in adults and children with type 1 diabetes. Current challenges and considerations for post-meal glucose control will also be discussed. Despite promising results with meal detection, the fully automated CLS has yet failed to provide comparable glucose control to CLS with carbohydrate-matched bolus in the post-meal period. The latter strategy has been efficient in controlling post-meal glucose using different algorithms and in various settings, but at the cost of a meal carbohydrate counting burden for patients. Further improvements in meal detection algorithms or simplified meal-priming boluses may represent interesting avenues. The greatest challenges remain in regards to the pharmacokinetic and dynamic profiles of available rapid insulins as well as sensor accuracy and lag-time. New and upcoming faster acting insulins could provide important benefits. Multi-hormone CLS (eg, dual-hormone combining insulin with glucagon or pramlintide) and adjunctive therapy (eg, GLP-1 and SGLT2 inhibitors) also represent promising options. Meal glucose control with the artificial pancreas remains an important challenge for which the optimal strategy is still to be determined.
The aim of this randomized four-way cross-over study was to examine the effect of added protein and/or fat in standard meals with a fixed carbohydrate content on postprandial glucose control with closed-loop insulin delivery in adults with type 1 diabetes. Participants (n = 15) consumed breakfast meals with a fixed carbohydrate content (75 ± 1 g) and added protein and/or fat (35 ± 2 g): (1) carbohydrate-only (standard), (2) high protein (HP), (3) high fat (HF) and (4) high fat + protein (HFHP). The closed-loop insulin delivery algorithm generated insulin bolus and infusion rates. The addition of fat, protein or both did not impact 5-hour post-meal sensor glucose area under the curve (AUC) (main outcome), mean sensor glucose or glycaemic peak as compared with a standard meal (P > 0.05). However, time to glycaemic peak was delayed by 40 minutes (P = 0.03) and 5-hour post-meal basal insulin requirements were 39% higher (P = 0.04) with an HFHP meal compared with a standard meal. In conclusion, in the context of closed-loop insulin delivery, protein and/or fat meal content affects the timing of postprandial glycaemic peak, insulin requirements and late glycaemic excursion, without impacting overall 5-hour AUC.
The role of glucagon in the pathophysiology of diabetes has long been recognized, although its approved clinical use has so far been limited to the emergency treatment of severe hypoglycaemia. A novel use of glucagon as intermittent mini-boluses is proposed in the dual-hormone version (insulin and glucagon) of the external artificial pancreas. Short-term studies suggest that the incorporation of glucagon into artificial pancreas systems has the potential to further decrease hypoglycaemic risk and improve overall glucose control; however, the potential long-term safety and benefits also need to be investigated given the recognized systemic effects of glucagon. In the present report, we review the available animal and human data on the physiological functions of glucagon, as well as its pharmacological use, according to dosing and duration (acute and chronic). Along with its main role in hepatic glucose metabolism, glucagon affects the cardiovascular, renal, pulmonary and gastrointestinal systems. It has a potential role in weight reduction through its central satiety function and its role in increasing energy expenditure. Most of the pharmacological studies investigating the effects of glucagon have used doses exceeding 1 mg, in contrast to the mini-boluses used in the artificial pancreas. The available data are reassuring but comprehensive human studies using small but chronic glucagon doses that are close to the physiological ranges are lacking. We propose a list of variables that could be monitored during long-term trials of the artificial pancreas. Such trials should address the questions about the risk-benefit ratio of chronic glucagon use.
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