Reduced hypoglycemia and increased time in target using closed-loop insulin delivery during nights with or without antecedent afternoon exercise in type 1 diabetes

Jennifer L Sherr, Eda Cengiz, Cesar C Palerm, Bud Clark, Natalie Kurtz, Anirban Roy, Lori Carria, Martin Cantwell, William V Tamborlane, Stuart A Weinzimer, Jennifer L Sherr, Eda Cengiz, Cesar C Palerm, Bud Clark, Natalie Kurtz, Anirban Roy, Lori Carria, Martin Cantwell, William V Tamborlane, Stuart A Weinzimer

Abstract

Objective: Afternoon exercise increases the risk of nocturnal hypoglycemia (NH) in subjects with type 1 diabetes. We hypothesized that automated feedback-controlled closed-loop (CL) insulin delivery would be superior to open-loop (OL) control in preventing NH and maintaining a higher proportion of blood glucose levels within the target blood glucose range on nights with and without antecedent afternoon exercise.

Research design and methods: Subjects completed two 48-h inpatient study periods in random order: usual OL control and CL control using a proportional-integrative-derivative plus insulin feedback algorithm. Each admission included a sedentary day and an exercise day, with a standardized protocol of 60 min of brisk treadmill walking to 65-70% maximum heart rate at 3:00 p.m.

Results: Among 12 subjects (age 12-26 years, A1C 7.4±0.6%), antecedent exercise increased the frequency of NH (reference blood glucose<60 mg/dL) during OL control from six to eight events. In contrast, there was only one NH event each on nights with and without antecedent exercise during CL control (P=0.04 vs. OL nights). Overnight, the percentage of glucose values in target range was increased with CL control (P<0.0001). Insulin delivery was lower between 10:00 p.m. and 2:00 a.m. on nights after exercise on CL versus OL, P=0.008.

Conclusions: CL insulin delivery provides an effective means to reduce the risk of NH while increasing the percentage of time spent in target range, regardless of activity level in the mid-afternoon. These data suggest that CL control could be of benefit to patients with type 1 diabetes even if it is limited to the overnight period.

Trial registration: ClinicalTrials.gov NCT00831389.

Figures

Figure 1
Figure 1
Diagrammatic representation of clinical study procedures. BG, blood glucose.
Figure 2
Figure 2
Episodes of overnight treatable hypoglycemia (reference blood glucose

Figure 3

A : Overnight insulin delivery…

Figure 3

A : Overnight insulin delivery in units/h 7–11 h postexercise (10:00 p.m. to…
Figure 3
A: Overnight insulin delivery in units/h 7–11 h postexercise (10:00 p.m. to 2:00 a.m.), with CL associated with lower insulin delivery (P = 0.008). B: Plasma insulin levels between 10:00 p.m. and 2:00 a.m., with trend toward significance for lower plasma insulin levels on CL nights vs. OL nights (P = 0.06). CL-E, CL exercise (solid line); OL-E, OL exercise (dashed line).
Figure 3
Figure 3
A: Overnight insulin delivery in units/h 7–11 h postexercise (10:00 p.m. to 2:00 a.m.), with CL associated with lower insulin delivery (P = 0.008). B: Plasma insulin levels between 10:00 p.m. and 2:00 a.m., with trend toward significance for lower plasma insulin levels on CL nights vs. OL nights (P = 0.06). CL-E, CL exercise (solid line); OL-E, OL exercise (dashed line).

References

    1. Tsalikian E, Mauras N, Beck RW, et al. Diabetes Research In Children Network Direcnet Study Group Impact of exercise on overnight glycemic control in children with type 1 diabetes mellitus. J Pediatr 2005;147:528–534
    1. Jones TW, Porter P, Sherwin RS, et al. Decreased epinephrine responses to hypoglycemia during sleep. N Engl J Med 1998;338:1657–1662
    1. Banarer S, Cryer PE. Sleep-related hypoglycemia-associated autonomic failure in type 1 diabetes: reduced awakening from sleep during hypoglycemia. Diabetes 2003;52:1195–1203
    1. McMahon SK, Ferreira LD, Ratnam N, et al. Glucose requirements to maintain euglycemia after moderate-intensity afternoon exercise in adolescents with type 1 diabetes are increased in a biphasic manner. J Clin Endocrinol Metab 2007;92:963–968
    1. Tamborlane WV. Triple jeopardy: nocturnal hypoglycemia after exercise in the young with diabetes. J Clin Endocrinol Metab 2007;92:815–816
    1. Tamborlane WV, Beck RW, Bode BW, et al. Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med 2008;359:1464–1476
    1. Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group Prolonged nocturnal hypoglycemia is common during 12 months of continuous glucose monitoring in children and adults with type 1 diabetes. Diabetes Care 2010;33:1004–1008
    1. Battelino T, Conget I, Olsen B, et al. SWITCH Study Group The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial. Diabetologia 2012;55:3155–3162
    1. Beck RW, Tamborlane WV, Bergenstal RM, Miller KM, DuBose SN, Hall CA, T1D Exchange Clinic Network The T1D Exchange clinic registry. J Clin Endocrinol Metab 2012;97:4383–4389
    1. Steil GM, Rebrin K, Darwin C, Hariri F, Saad MF. Feasibility of automating insulin delivery for the treatment of type 1 diabetes. Diabetes 2006;55:3344–3350
    1. Weinzimer SA, Steil GM, Swan KL, Dziura J, Kurtz N, Tamborlane WV. Fully automated closed-loop insulin delivery versus semiautomated hybrid control in pediatric patients with type 1 diabetes using an artificial pancreas. Diabetes Care 2008;31:934–939
    1. Renard E, Place J, Cantwell M, Chevassus H, Palerm CC. Closed-loop insulin delivery using a subcutaneous glucose sensor and intraperitoneal insulin delivery: feasibility study testing a new model for the artificial pancreas. Diabetes Care 2010;33:121–127
    1. Castle JR, Engle JM, El Youssef J, et al. Novel use of glucagon in a closed-loop system for prevention of hypoglycemia in type 1 diabetes. Diabetes Care 2010;33:1282–1287
    1. El-Khatib FH, Russell SJ, Nathan DM, Sutherlin RG, Damiano ER. A bihormonal closed-loop artificial pancreas for type 1 diabetes. Sci Transl Med 2010;2:27ra27.
    1. Kovatchev B, Cobelli C, Renard E, et al. Multinational study of subcutaneous model-predictive closed-loop control in type 1 diabetes mellitus: summary of the results. J Diabetes Sci Tech 2010;4:1374–1381
    1. Hovorka R, Kumareswaran K, Harris J, et al. Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies. BMJ. 2011;342:d1855
    1. Hovorka R, Allen JM, Elleri D, et al. Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet 2010;375:743–751
    1. Palerm CC. Physiologic insulin delivery with insulin feedback: a control systems perspective. Comput Methods Programs Biomed 2011;102:130–137
    1. Steil GM, Palerm CC, Kurtz N, et al. The effect of insulin feedback on closed loop glucose control. J Clin Endocrinol Metab 2011;96:1402–1408
    1. Ruiz JL, Sherr JL, Cengiz E, et al. Effect of insulin feedback on closed-loop glucose control: a crossover study. J Diabetes Sci Tech 2012;6:1123–1130
    1. Weinzimer SA, Sherr JL, Cengiz E, et al. Effect of pramlintide on prandial glycemic excursions during closed-loop control in adolescents and young adults with type 1 diabetes. Diabetes Care 2012;35:1994–1999
    1. Tsalikian E, Kollman C, Tamborlane WB, et al. Diabetes Research in Children Network (DirecNet) Study Group Prevention of hypoglycemia during exercise in children with type 1 diabetes by suspending basal insulin. Diabetes Care 2006;29:2200–2204
    1. Taplin CE, Cobry E, Messer L, McFann K, Chase HP, Fiallo-Scharer R. Preventing post-exercise nocturnal hypoglycemia in children with type 1 diabetes. J Pediatr 2010;157:784.e1–788.e1
    1. Phillip M, Battelino T, Atlas E, et al. Nocturnal glucose control with an artificial pancreas at a diabetes camp. N Engl J Med 2013;368:824–833
    1. Nimri R, Atlas E, Ajzensztejn M, Miller S, Oron T, Phillip M. Feasibility study of automated overnight closed-loop glucose control under MD-logic artificial pancreas in patients with type 1 diabetes: the DREAM Project. Diabetes Technol Ther 2012;14:728–735
    1. Russell SJ, El-Khatib FH, Nathan DM, Magyar KL, Jiang J, Damiano ER. Blood glucose control in type 1 diabetes with a bihormonal bionic endocrine pancreas. Diabetes Care 2012;35:2148–2155

Source: PubMed

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