PracticeUpdate: Endocrinology

FEATURE ARTICLE

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Improved glycaemic control with closed-loop insulin in pregnant diabetic women By Jennifer Sherr, MD, PhD

Upcoming Endocrinology conferences 2016 OCTOBER 13–15 October | Seoul, South Korea International Conference on Diabetes and Metabolism 2016 icdm2016.diabetes.or.kr

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31 October–4 November | New Orleans, USA The Obesity Society: Annual Scientific Meeting www.obesity.org/meetings/obesity-week NOVEMBER 7–9 November | Brighton, UK Society for Endocrinology BES 2016 www.endocrinology.org/ meetings/2016/sfebes2016

Just as closed-loop insulin delivery studies have progressed from being performed solely in supervised, inpatient research centres to home environments with no remote monitoring, the population being studied has expanded. Recently, these systems have been assessed in those with type 1 diabetes deemed as vulnerable populations – including young children 1,2 and pregnant women. 3,4

E xtending on their previous work, the study “Closed-loop insulin delivery during pregnancy in women with type 1 diabetes” by Stewart and colleagues was an open-label, randomised crossover assess- ment examining overnight glucose control following 4 weeks of closed-loop therapy compared with 4 weeks of sensor-augmented pump therapy (SAP). 5 The system used was the Florence D2W closed-loop system. The system is comprised of a FreeStyle Naviga- tor II that was linked via a cable to a Dell Latitude 10 tablet, which housed the model predictive control algorithm that commu- nicated via Bluetooth with the DANA Diabecare R insulin pump to deliver insulin based on algorithm calculations every 12 minutes. The treat-to-target algorithm was set with glucose targets between 97 and 124 mg/dL (5.38 and 6.88 mmol/L). The system was initialised using preprogramed basal rates, total daily insulin doses, and the participants’ weights. In all, 16 women completed all study- related procedures (mean age, 34 ± 4 years; A1c, 6.8 ± 0.6%; duration of diabetes, 23.6 ± 7 years; week of gestation at randomisa- tion, 14 ± 3.3 weeks). The primary outcome was the percentage of time that overnight glucose levels were within the target range (63–140 mg/dL [3.50–7.77 mmol/L]). Use of closed-loop insulin delivery increased the time in target by 15% (closed-loop 74.7% vs SAP 59.5%; P = 0.002). Average glucose was lower with closed-loop control both overnight and over a 24-hour period (overnight, P = 0.009; 24-hour period, P < 0.001). There was no difference in the time

In pregnancy, when insulin requirements frequently change and there is substantial day-to-day glycaemic variability, the closed-loop system can help expectant mothers achieve more targeted glycaemic control. Importantly, this was achieved without any changes in the programming to the system.

11–12 November | Vienna, Austria Prevention Models of Obesity and Cardiovascular Diseases International Symposium 2016 www.poc-vienna-2016.eu DECEMBER 1–3 December | Universal City, California, USA 14th Annual World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease 2016 wcir.org

spent in the hypoglycaemic range between the two study conditions (P = 0.28). Continued use of the closed-loop system was offered to participants at the end of the randomised trial, with 14 participants (~90%) choosing this option. The median time in the continuation phase was ~11.6 weeks, and mean glucose achieved during this period was 126 mg/dL (6.99 mmol/L), with 68.7% of time in target. This continu- ation phase encompassed use of the system both during labour and after delivery. Time in target was 86.8% in the 24 hours prior to delivery and 73.7% in the 48 hours post- delivery. The system adeptly adjusted insulin delivery, reducing it 53% from pre-delivery doses in the post-delivery period. As maternal hyperglycaemia impacts fetal growth, the achievement of more targeted control through closed-loop use has the potential to minimise excessive weight gain. The vast majority of infants in the present study were categorised as large for gestational age. With no change in rates of hypoglycaemia and no episodes of severe hypoglycaemia in either study condition, it may be feasible to make the algorithm more aggressive in future studies. Stewart and colleagues have demon- strated that, in pregnancy, when insulin requirements frequently change and there is

substantial day-to-day glycaemic variability, the closed-loop system can help expectant mothers achieve more targeted glycaemic control. Importantly, this was achieved without any changes in the programming to the system. With the clear-cut benefits of closed-loop therapy in this population, the next steps should be application of such technologies prior to conception with use extending for the duration of the pregnancy to further determine how it can impact both maternal and neonatal outcomes. References 1. Ruan Y, Elleri D, Allen JM, et al. Diabetologia 2015;58:687-690. 2. Dauber A, Corcia L, Safer J, et al. Diabetes Care 2013;36:222-227. 3. Murphy HR, Elleri D, Allen JM, et al. Diabetes Care 2011;34:406-411. 4. Murphy HR, Kumareswaran K, Elleri D, et al. Dia- betes Care 2011;34:2527-2529. 5. Stewart ZA, Wilinska ME, Hartnell S, et al. N Engl J Med 2016;375:644-654. Dr Sherr is Instructor, Pediatrics (Endocrinology), Yale University School of Medicine, New Haven, Connecticut. Her research has focused on artificial pancreas technologies and the use

2–4 December | Atlanta, USA 9th World Congress on Prevention of Diabetes

and its Complications 2016 www.wcpd9.com/home.php

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of adjunctive therapy to mitigate postprandial hyperglycaemia.

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VOL. 1 • No. 3 • 2016