The proposed research focuses on the changes in glucose/insulin dynamics in type 1 diabetes mellitus (T1DM) patients during and after exercise and their quantification via metabolic modeling. Once identified and quantified these dynamics can be used to adapt insulin delivery in response to physical activity and therefore avoid under or over estimation of insulin needs. Exercise can be either announced, or detected via heart rate monitoring. Addition of heart rate monitoring would allow to minimize the hypo- and hyperglycemic episodes frequently following over or under compensation for exercise. Such an optimization would be applicable to standard insulin treatment (basal and meal boluses), open loop glycemic control (adaptive basal and bolus patterns), and will be critical in any closed loop applications. Recent advancements in diabetes technology include two rapidly evolving parallel areas: insulin delivery devices (subcutaneous or implanted insulin pumps) and continuous glucose monitors (CGM) recording frequent glucose determinations. Preliminary studies have now demonstrated that these two types of devices can be linked successfully in a closed-loop glucose control system but it remains to be shown how these systems will react to metabolic disturbances not triggered by meals, such as exercise. Physical activity has been widely recognized as an essential element of the treatment of patients with T1DM patients. However, certain risks and adverse events are associated with exercise, including hypoglycemia. Recent studies in both adult and pediatric populations have demonstrated that patients suffered immediate and late onset hypoglycemic events both if insulin delivery was kept normal, was reduced, and when it was completely stopped during exercise. Moreover, currently tested closed loop glucose control systems solely rely on continuous glucose monitors (CGM) and pump injection feedback and their performance deteriorates when challenged with physical activity. The addition of heart rate as an input signal will allow such systems to detect and react to physical activity;therefore avoiding hypoglycemia both during and most importantly in the hours after a bout of physical activity. The proposed study is organized in two consecutive phases, system engineering and a clinical trial. Consequently we designed this exploratory study with three principal goals;(i) introduce heart rate as a new metabolic signal in T1DM insulin treatment;(ii) investigate the performances of an artificial pancreas system during and after exercise in T1DM patients;(iii) augment our currently tested artificial pancreas system using heart rate as an exercise marker, targeting avoidance of hypoglycemia post physical activity. We hypothesize that the use of heart rate monitoring will restore the protection against hypoglycemia and postprandial excursion observed during the control condition. Specifically it will result in (i) reduced occurrence of hypoglycemia;(ii) deviation from a euglycemic glucose target;(iii) increased glucose system stability.

Public Health Relevance

Our study is significant because it focuses on the main impediment to tight glycemic control in type 1 diabetes patients: physical activity. The overall goals of this work is to understand the consequences of moderate exercise on the action of insulin and developing a new generation of glucose control systems that use heart rate as an indicator of physical activity and quantitatively inform the insulin regimen of a patient.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZDK1-GRB-2 (O2))
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Arreaza-Rubin, Guillermo
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University of Virginia
Schools of Medicine
United States
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Breton, Marc D; Brown, Sue A; Karvetski, Colleen Hughes et al. (2014) Adding heart rate signal to a control-to-range artificial pancreas system improves the protection against hypoglycemia during exercise in type 1 diabetes. Diabetes Technol Ther 16:506-11
Lv, Dayu; Breton, Marc D; Farhy, Leon S (2013) Pharmacokinetics modeling of exogenous glucagon in type 1 diabetes mellitus patients. Diabetes Technol Ther 15:935-41
Breton, Marc; Farret, Anne; Bruttomesso, Daniela et al. (2012) Fully integrated artificial pancreas in type 1 diabetes: modular closed-loop glucose control maintains near normoglycemia. Diabetes 61:2230-7