• 1
    Rewers A, Klingensmith G, Davis C et al. Presence of diabetic ketoacidosis at diagnosis of diabetes mellitus in youth: the Search for Diabetes in Youth Study. Pediatrics 2008; 121: e1258e1266.
  • 2
    Svensson M, Eriksson JW, Dahlquist G. Early glycemic control, age at onset, and development of microvascular complications in childhood-onset type 1 diabetes: a population-based study in northern Sweden. Diabetes Care 2004; 27: 955962.
  • 3
    Olsen BS, Johannesen J, Sjolie AK et al. Metabolic control and prevalence of microvascular complications in young Danish patients with Type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood. Diabet Med 1999; 16: 7985.
  • 4
    The EURODIAB IDDM Complications Study Group. Microvascular and acute complications in IDDM patients: the EURODIAB IDDM Complications Study. Diabetologia 1994; 37: 278–285.
  • 5
    The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl J Med 2000; 342: 381–389.
  • 6
    Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA 2003; 290: 21592167.
  • 7
    Kumareswaran K, Evans ML, Hovorka R. Artificial pancreas: an emerging approach to treat Type 1 diabetes. Expert Rev Med Devices 2009; 6: 401410.
  • 8
    Lorenzi M, Bohannon N, Tsalikian E, Karam JH. Duration of type I diabetes affects glucagon and glucose responses to insulin-induced hypoglycemia. West J Med 1984; 141: 467471.
  • 9
    Cryer PE. Hypoglycemia, functional brain failure, and brain death. J Clin Invest 2007; 117: 868870.
  • 10
    Pickup JC, Freeman SC, Sutton AJ. Glycaemic control in type 1 diabetes during real time continuous glucose monitoring compared with self monitoring of blood glucose: meta-analysis of randomised controlled trials using individual patient data. BMJ 2011; 343: d3805.
  • 11
    Langendam M, Luijf YM, Hooft L, Devries JH, Mudde AH, Scholten RJ. Continuous glucose monitoring systems for type 1 diabetes mellitus. Cochrane Database Syst Rev 2012; 1: CD008101.
  • 12
    Holmes G, Galitz L, Hu P, Lyness W. Pharmacokinetics of insulin aspart in obesity, renal impairment, or hepatic impairment. Br J Clin Pharmacol 2005; 60: 469476.
  • 13
    Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group, Tamborlane WV, Beck RW et al. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med 2008; 359: 14641476.
  • 14
    Retnakaran R, Hochman J, DeVries JH et al. Continuous subcutaneous insulin infusion versus multiple daily injections: the impact of baseline A1c. Diabetes Care 2004; 27: 25902596.
  • 15
    Pickup J, Mattock M, Kerry S. Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials. BMJ 2002; 324: 705.
  • 16
    Buse JB, Dailey G, Ahmann AA et al. Baseline predictors of A1C reduction in adults using sensor-augmented pump therapy or multiple daily injection therapy: the STAR 3 experience. Diabetes Technol Ther 2011; 13: 601606.
  • 17
    Kadish AH. Automation control of blood sugar. I. a Servomechanism for glucose monitoring and control. Am J Med Electron 1964; 3: 8286.
  • 18
    Albisser AM, Leibel BS. The artificial pancreas. Clin Endocrinol Metab 1977; 6: 457479.
  • 19
    Kovatchev B. Closed loop control for type 1 diabetes. BMJ 2011; 342: 1911.
  • 20
    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.
  • 21
    Ward WK, Castle JR, El YJ. Safe glycemic management during closed-loop treatment of type 1 diabetes: the role of glucagon, use of multiple sensors, and compensation for stress hyperglycemia. J Diabetes Sci Technol 2011; 5: 13731380.
  • 22
    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.
  • 23
    Buckingham B, Chase HP, Dassau E et al. Prevention of nocturnal hypoglycemia using predictive alarm algorithms and insulin pump suspension. Diabetes Care 2010; 33: 10131017.
  • 24
    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: 728735.
  • 25
    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: 934939.
  • 26
    Heinemann L, Benesch C, DeVries JH. AP@home: a novel European approach to bring the artificial pancreas home. J Diabetes Sci Technol 2011; 5: 13631372.
  • 27
    Juvenile Diabetes Research Foundation Artificial Pancreas Consortium. Available from URL: Accessed 2 September 2013.
  • 28
    The AP@home Consortium. Available from URL Accessed 2 October 2013.
  • 29
    Kovatchev BP, Breton M, Man CD, Cobelli C. In silico preclinical trials: a proof of concept in closed-loop control of type 1 diabetes. J Diabetes Sci Technol 2009; 3: 4455.
  • 30
    Castle JR, Ward WK. Amperometric glucose sensors: sources of error and potential benefit of redundancy. J Diabetes Sci Technol 2010 1; 4: 221225.
  • 31
    Fogt EJ, Dodd LM, Jenning EM, Clemens AH. Development and evaluation of a glucose analyzer for a glucose controlled insulin infusion system (Biostator). Clin Chem 1978; 24: 13661372.
  • 32
    El-Khatib FH, Jiang J, Damiano ER. Adaptive closed-loop control provides blood-glucose regulation using dual subcutaneous insulin and glucagon infusion in diabetic Swine. J Diabetes Sci Technol 2007; 1: 181192.
  • 33
    Ward W, Engle J, Duman H, Bergstrom C, Kim S, Federiuk I. The benefit of subcutaneous glucagon during closed-loop glycemic control in rats with type 1 diabetes. IEEE Sensors J 2008; 8: 8896.
  • 34
    Hovorka R. Closed-loop insulin delivery: from bench to clinical practice. Nat Rev Endocrinol 2011; 7: 385395.
  • 35
    Parker RS, 3rd Doyle FJ, Peppas NA. A model-based algorithm for blood glucose control in type I diabetic patients. IEEE Trans Biomed Eng 1999; 46: 148157.
  • 36
    Steil GM, Panteleon AE, Rebrin K. Closed-loop insulin delivery-the path to physiological glucose control. Adv Drug Deliv Rev 2004; 56: 125144.
  • 37
    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: 33443350.
  • 38
    Elleri D, Allen JM, Nodale M et al. Automated overnight closed-loop glucose control in young children with type 1 diabetes. Diabetes Technol Ther 2011; 13: 419424.
  • 39
    Murphy HR, Kumareswaran K, Elleri D et al. Safety and efficacy of 24-h closed-loop insulin delivery in well-controlled pregnant women with type 1 diabetes: a randomized crossover case series. Diabetes Care 2011; 34: 25272529.
  • 40
    Bruttomesso D, Farret A, Costa S et al. Closed-loop artificial pancreas using subcutaneous glucose sensing and insulin delivery and a model predictive control algorithm: preliminary studies in Padova and Montpellier. J Diabetes Sci Technol 2009; 3: 10141021.
  • 41
    Clarke WL, Anderson S, Breton M, Patek S, Kashmer L, Kovatchev B. Closed-loop artificial pancreas using subcutaneous glucose sensing and insulin delivery and a model predictive control algorithm: the Virginia experience. J Diabetes Sci Technol 2009; 3: 10311038.
  • 42
    Chassin L, Wilinska M, Hovorka R. Evaluation of glucose controllers in virtual environment: methodology and sample application. Artif Intell Med 2004; 32: 171181.
  • 43
    Atlas E, Nimri R, Miller S, Grunberg EA, Phillip M. MD-logic artificial pancreas system: a pilot study in adults with type 1 diabetes. Diabetes Care 2010; 33: 10721076.
  • 44
    Renard E. Insulin delivery route for the artificial pancreas: subcutaneous, intraperitoneal, or intravenous? Pros and cons. J Diabetes Sci Technol 2008; 2: 735738.
  • 45
    Liebl A, Hoogma R, Renard E et al. A reduction in severe hypoglycaemia in type 1 diabetes in a randomized crossover study of continuous intraperitoneal compared with subcutaneous insulin infusion. Diabetes Obes Metab 2009; 11: 10011008.
  • 46
    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: 121127.
  • 47
    Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group. Effectiveness of continuous glucose monitoring in a clinical care environment: evidence from the Juvenile Diabetes Research Foundation continuous glucose monitoring (JDRF-CGM) trial. Diabetes Care 2010; 33: 1722.
  • 48
    Mastrototaro J, Shin J, Marcus A, Sulur G, STAR 1 Clinical Trial Investigators. The accuracy and efficacy of real-time continuous glucose monitoring sensor in patients with type 1 diabetes. Diabetes Technol Ther 2008; 10: 385390.
  • 49
    Hirsch IB, Abelseth J, Bode BW et al. Sensor-augmented insulin pump therapy: results of the first randomized treat-to-target study. Diabet Tech Ther 2008; 10: 377383.
  • 50
    Slover RH, Welsh JB, Criego A et al. Effectiveness of sensor-augmented pump therapy in children and adolescents with type 1 diabetes in the STAR 3 study. Pediatr Diabetes 2012; 13: 611.
  • 51
    Hermanides J, Norgaard K, Bruttomesso D et al. Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type 1 diabetes; a randomized controlled trial. Diabet Med 2011; 28: 11581167.
  • 52
    Garg S, Brazg RL, Bailey TS et al. Reduction in duration of hypoglycemia by automatic suspension of insulin delivery: the in-clinic ASPIRE study. Diabetes Technol Ther 2012; 14: 205209.
  • 53
    Cengiz E, Swan KL, Tamborlane WV, Steil GM, Steffen AT, Weinzimer SA. Is an automatic pump suspension feature safe for children with type 1 diabetes? An exploratory analysis with a closed-loop system. Diabetes Technol Ther 2009; 11: 207210.
  • 54
    Ly TT, Nicholas JA, Retterath A, Davis EA, Jones TW. Analysis of glucose responses to automated insulin suspension with sensor-augmented pump therapy. Diabetes Care 2012; 35: 14621465.
  • 55
    Choudhary P, Shin J, Wang Y et al. Insulin pump therapy with automated insulin suspension in response to hypoglycemia: reduction in nocturnal hypoglycemia in those at greatest risk. Diabetes Care 2011; 34: 20232025.
  • 56
    Danne T, Kordonouri O, Holder M et al. Prevention of hypoglycemia by using low glucose suspend function in sensor-augmented pump therapy. Diabetes Technol Ther 2011; 13: 11291134.
  • 57
    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: 12821287.
  • 58
    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: 21482155.
  • 59
    Haidar A, Legault L, Dallaire M, et al. Glucose-responsive insulin and glucagon delivery (dual-hormone artificial pancreas) in adults with type 1 diabetes: a randomized crossover controlled trial. CMAJ 2013.
  • 60
    Castle JR, Engle JM, El Youssef J, Massoud RG, Ward WK. Factors influencing the effectiveness of glucagon for preventing hypoglycemia. J Diabetes Sci Technol 2010; 4: 13051310.
  • 61
    El Youssef J, Castle JR, Branigan DL et al. A controlled study of the effectiveness of an adaptive closed-loop algorithm to minimize corticosteroid-induced stress hyperglycemia in type 1 diabetes. J Diabetes Sci Technol 2011; 5: 13121326.
  • 62
    Van Bon AC, Jonker LD, Koebrugge R, Koops R, Hoekstra JB, DeVries JH. Feasibility of a bihormonal closed-loop system to control postexercise and postprandial glucose excursions. J Diabetes Sci Technol 2012; 6: 11141122.
  • 63
    Graf CJ, Woodworth JR, Seger ME, Holcombe JH, Bowsher RR, Lynch R. Pharmacokinetic and glucodynamic comparisons of recombinant and animal-source glucagon after IV, IM, and SC injection in healthy volunteers. J Pharm Sci 1999; 88: 991995.
  • 64
    Ward WK, Massoud RG, Szybala CJ et al. In vitro and in vivo evaluation of native glucagon and glucagon analog (MAR-D28) during aging: lack of cytotoxicity and preservation of hyperglycemic effect. J Diabetes Sci Technol 2010; 4: 13111321.
  • 65
    Onoue S, Ohshima K, Debari K et al. Mishandling of the therapeutic peptide glucagon generates cytotoxic amyloidogenic fibrils. Pharm Res 2004; 21: 12741283.
  • 66
    Pedersen JS, Dikov D, Flink JL, Hjuler HA, Christiansen G, Otzen DE. The changing face of glucagon fibrillation: structural polymorphism and conformational imprinting. J Mol Biol 2006; 355: 501523.
  • 67
    Maji SK, Perrin MH, Sawaya MR et al. Functional amyloids as natural storage of peptide hormones in pituitary secretory granules. Science 2009; 325: 328332.
  • 68
    Matilainen L, Maunu SL, Pajander J et al. The stability and dissolution properties of solid glucagon/gamma-cyclodextrin powder. Eur J Pharm Sci 2009; 36: 412420.
  • 69
    Cobelli C, Renard E, Kovatchev BP et al. Pilot studies of wearable outpatient artificial pancreas in type 1 diabetes. Diabetes Care 2012; 35: e65e67.
  • 70
    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: 824833.
  • 71
    Raz I, Weiss R, Yegorchikov Y, Bitton G, Nagar R, Pesach B. Effect of a local heating device on insulin and glucose pharmacokinetic profiles in an open-label, randomized, two-period, one-way crossover study in patients with type 1 diabetes using continuous subcutaneous insulin infusion. Clin Ther 2009; 31: 980987.
  • 72
    Vaughn DE, Yocum RC, Muchmore DB et al. Accelerated pharmacokinetics and glucodynamics of prandial insulins injected with recombinant human hyaluronidase. Diabetes Technol Ther 2009; 11: 345352.
  • 73
    Hompesch M, Muchmore DB, Morrow L, Vaughn DE. Accelerated insulin pharmacokinetics and improved postprandial glycemic control in patients with type 1 diabetes after coadministration of prandial insulins with hyaluronidase. Diabetes Care 2011; 34: 666668.
  • 74
    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: 19941999.
  • 75
    Castle JR, Pitts A, Hanavan K et al. The accuracy benefit of multiple amperometric glucose sensors in people with type 1 diabetes. Diabetes Care 2012; 35: 706710.