Sensor Augmented Pump Therapy Use in Type 1 Diabetes Mellitus
E Carolan, NP Murphy
Department of Diabetes & Endocrinology, Children’s University Hospital, Temple St, Dublin 1.
Tight metabolic control in Type 1 Diabetes Mellitus (T1DM) reduces incidence and delays progression of micro-vascular complications. Severe hypoglycaemia remains a significant barrier to achieving optimal diabetes control. Continuous subcutaneous insulin infusion (CSII) systems refine insulin delivery with programmable basal rates and mealtime bolusing. Continuous glucose monitoring (CGM), using interstitial glucose sensors, aims to provide a more composite understanding of minute-to-minute glucose variability. Merging of both devices has resulted in sensor-augmented insulin pump (SAP) therapy. Artificial beta cell or closed loop insulin delivery systems expand on this concept by using a control algorithm to autonomously continually alter delivered insulin on the basis of real time sensor glucose levels. Recently the first randomized control trial (RCT) outside a research facility compared the closed loop system to existing SAP, and reported an advantage with the closed loop system in hypoglycaemic risk and blood glucose control1. Closed loop systems are not yet available commercially.
Standard CSII, first developed over 30 years ago, has become increasingly popular since the Diabetes Control and Complications Trial described a beneficial effect of intensive diabetes management on complication prevention2. CSII has proved successful in improving metabolic control in T1DM3. Current pump devices are reliable, have built-in dosage calculators and device malfunction alarms. CGM systems utilize glucose oxidase-based, electrochemical sensors that are inserted through the skin by a needle introducer. Interstitial glucose oxidation by the sensor generates an electrical current. Interstitial fluid (IF) glucose rather than capillary blood glucose measurements poses some difficulties4. Many factors alter the way that glucose is transferred to the IF space, and as a result a lag time of 15 minutes in detecting blood glucose ensues. Glucose sensors must be calibrated against a blood glucose meter when glucose levels are stable to ensure accuracy of sensor data5. Real-time CGM systems continuously display current interstitial glucose concentration.
Near continuous use of CGM (used 6 of 7 days/week) improves HbA1c significantly6. Studies in T1DM youths show significantly less sustained CGM use than adults and therefore reduced glycaemic control advantage. Although CGM provides unparalleled data, there are a number of barriers that may prohibit individuals from wearing the device. CGM use may add to the burden of daily diabetes management7. A study examining satisfaction levels of CGM use in youth, their parents, and adults described pain associated with sensor insertion, nuisance alarms, sensor placement frustration, sensor-adhesive skin reactions and receiver carriage on the body as the most common barriers to device use8. Two integrated systems comprising continuous glucose monitor and insulin pump in a single device exist; the Medtronic MiniMed ÒVeoTMand Animas Ò VibeTM insulin pump/CGM system. They allow individuals to wear a glucose sensor for 7 days that will transmit glucose levels to the insulin pump. Updated glucose levels are transmitted to the pump every 5 minutes and glucose display graphs are visible for variable intervals. The Medtronic MiniMed ÒVeoTM also has the added feature of low-glucose suspend.
O’Connell et al investigated the use of real time CGM with CSII in a RCT comparison to standard insulin pump regimen in 62 T1DM participants aged between 13-40 years over a 12-week period9. HbA1c levels significantly improved (-0.43%, p=0.009) in the CGM/CSII group compared to the control group. Additional lowering of HbA1c levels was observed with CGM device use for more than 70% of the 3-month study duration. Compliance with frequent SAP device was suboptimal with one third of patients not completing the study due to alarm burden, skin irritation or transmitter issues. In the STAR3 (Study of Sensor-Augmented Pump Therapy for A1C Reduction), T1DM patients were randomized to 1-year of SAP therapy or MDI10. In this multi-center RCT, baseline mean HbA1c of 8.3% decreased to 7.5% in the sensor-augmented pump group and to 8.1% in the MDI group, a significant difference of 0.8% (p<0.001). In the pediatric participant group, individuals with SAP therapy were more likely to attain ADA age-specific target HbA1c values than injection-treated patient11. Kordonouri et al assessed SAP therapy at T1DM onset in youth, randomizing patients to either SAP therapy or CSII therapy12. HbA1c remained the same between study groups at all time points with infrequent sensor use among pediatric patients the main barrier to its routine use.
Low-glucose suspend (LGS) functionality is a recent addition to SAP therapy which results in automatic suspension of pump basal insulin on sensor detection of sustained hypoglycemia. As nocturnal hypoglycemia remains a significant concern for T1DM patients, a RCT was conducted to determine frequency in adults using SAP therapy with or without the threshold-suspend feature. Nocturnal hypoglycaemic events occurred 31.8% less frequently in the LGS group compared to the control group (p<0.001)13. Similar findings were described in a study of LGS use in children and adolescents14. Mean occurrence of hypoglycaemic excursions <3.8mmol/l was reduced from 1.27 to 0.95 times daily (p=0.01) suggesting that the LGS feature could aid in prevention of nocturnal hypoglycemic episodes. The UK National Institute for Clinical Excellence (NICE) health technology evaluation has recently recommended SAP with LGS (Minimed paradigm Veo) for prevention of hypoglycemia in patients with type 1 diabetes who agree to wear the sensor > 70% of the time15.
Technological advances in glucose monitoring and insulin delivery continue to increase available therapeutic options for patients. Study results are promising, but present benefits are limited to those individuals who are able to wear the CGM devices near continuously. This benefit must be carefully balanced against the risk of increased self-care burden and burnout, and further large-scale studies are required. The use of continuous glucose monitors and sensor-augmented pumps should be carefully considered for T1DM patients on an individual basis pending availability of true closed loop systems.
Nuala Murphy, Department of Diabetes & Endocrinology, Children’s University Hospital, Temple St, Dublin 1
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- The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The New England Journal of Medicine. 1993;329(14):977-86.
- Ahern JA, Boland EA, Doane R, Ahern JJ, Rose P, Vincent M, Tamborlane WV. Insulin pump therapy in pediatrics: a therapeutic alternative to safely lower HbA1c levels across all age groups. Pediatric Diabetes. 2002;3(1):10-5.
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- Rebrin K, Steil GM. Can interstitial glucose assessment replace blood glucose measurements? Diabetes Technology & Therapeutics. 2000;2:461-72.
- Langendam M, Luijf YM, Hooft L, Devries JH, Mudde AH, Scholten RJ. Continuous glucose monitoring systems for type 1 diabetes mellitus. The Cochrane Database of Systematic Reviews. 2012;1:CD008101.
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- Tansey M, Laffel L, Cheng J, Beck R, Coffey J, Huang E, Kollman C, Lawrence J, Lee J, Ruedy K, Tamborlane W, Wysocki T, Xing D, Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Satisfaction with continuous glucose monitoring in adults and youths with Type 1 diabetes. Diabetic Medicine. 2011;28:1118-22.
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- Bergenstal RM, Tamborlane WV, Ahmann A, Buse JB, Dailey G, Davis SN, Joyce, C. Peoples T, Perkins, BA, Welsh JB, Willi SM, Wood MA, Star Study Group. Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes. The New England Journal of Medicine. 2010;363:311-20.
- Slover RH, Welsh JB, Criego A, Weinzimer SA, Willi SM, Wood MA, Tamborlane WV. Effectiveness of sensor-augmented pump therapy in children and adolescents with type 1 diabetes in the STAR 3 study. Pediatric Diabetes. 2012;13:6-11.
- Kordonouri O, Pankowska E, Rami B, Kapellen T, Coutant R, Hartmann R, Lange K, Knip M, Danne T. Sensor-augmented pump therapy from the diagnosis of childhood type 1 diabetes: results of the Paediatric Onset Study (ONSET) after 12 months of treatment. Diabetologia. 2010;53:2487-95.
- Bergenstal RM, Klonoff DC, Garg SK, Bode BW, Meredith M, Slover RH, Ahmann AJ, Welsh JB, Lee SW, Kaufman FR, Aspire In-Home Study Group. Threshold-based insulin-pump interruption for reduction of hypoglycemia. The New England Journal of Medicine. 2013;369(3):224-32.
- Danne T, Kordonouri O, Holder M, Haberland H, Golembowski S, Remus K, Blasig S, Wadien T, Zierow S, Hartmann R, Thomas, A. Prevention of hypoglycemia by using low glucose suspend function in sensor-augmented pump therapy. Diabetes Technology & Therapeutics. 2011;13:1129-34.
- National Institute for Health and Care Excellence. Type 1 diabetes: Integrated sensor-augmented pump therapy systems for managing blood glucose levels. – the MiniMed Paradigm Veo system and the Vibe and G4 PLATINUM CGM system. (Feb 2016) Available from website: https://www.nice.org.uk/guidance/indevelopment/gid-dt22