Information

Related Research Units

Critical Care Medicine Research
Medicine Critical Care Research

Research Overview

The importance of maintaining blood glucose levels within a narrow target range is well established in both the critical care setting and day-to-day lives of individuals with diabetes. In the critical care setting high blood glucose, known as stress hyperglycemia, occurs when the body’s insulin producing â-cells cannot meet the increased demand for insulin brought about as a result of the underlying critical illness1. This is similar to the conditions underlying type 2 diabetes, where the body again cannot make sufficient insulin to bring glucose levels under control, and the condition in type 1 diabetes, where the body’s â-cells have been destroyed by an underlying immune disorder. In the ICU, stress hyperglycemia has immediate detrimental effects including possibly an increased risk of mortality; in individuals with diabetes the detrimental effects can slowly manifest over time.

Dr. Steil’s research at BCH seeks to combine continuous glucose monitoring (CGM) technologies developed to aid individuals with diabetes, with insulin dosing strategies derived from understanding of how the â-cell controls blood glucose when able2. His initial research in this area was targeted toward developing an artificial pancreas3 for individuals with type 1 diabetes. Those efforts continue today, with the focus now on younger children with diabetes4. The research has also be expanded to effect better glucose control in the ICU5, 6.

Research Background

Dr. Steil received a Ph.D. in Physiology and Biophysics from the University in Southern California, in Los Angeles California. Prior to receiving his Ph.D. he received a B.Sc. and a M.Sc., both in Electrical Engineering, from the University of Alberta in Edmonton Alberta Canada. He also worked as postdoctoral fellow at the Joslin Diabetes Center in Boston looking for new ways to transplant islets (another approach to addressing the insulin deficiency in type 1 diabetes), as well as in industry where he sought to develop the first commercially available artificial pancreas that could be made widely available to individuals with the disease.

 

Publications

  1. What Really Matters?: How Insulin Dose, Timing, and Distribution Relate to Meal Composition in Free-Living People with Type 1 Diabetes. Diabetes Technol Ther. 2025 Jan; 27(1):66-71. View Abstract
  2. Performance of an Electronic Decision Support System as a Therapeutic Intervention During a Multicenter PICU Clinical Trial: Heart and Lung Failure-Pediatric Insulin Titration Trial (HALF-PINT). Chest. 2021 09; 160(3):919-928. View Abstract
  3. Amount and Type of Dietary Fat, Postprandial Glycemia, and Insulin Requirements in Type 1 Diabetes: A Randomized Within-Subject Trial. Diabetes Care. 2020 01; 43(1):59-66. View Abstract
  4. Short-Term Adverse Outcomes Associated With Hypoglycemia in Critically Ill Children. Crit Care Med. 2019 05; 47(5):706-714. View Abstract
  5. Continuous Glucose Monitoring Linked to an Artificial Intelligence Risk Index: Early Footprints of Intraventricular Hemorrhage in Preterm Neonates. Diabetes Technol Ther. 2019 03; 21(3):146-153. View Abstract
  6. Adjusting Insulin Delivery to Activity (AIDA) clinical trial: Effects of activity-based insulin profiles on glucose control in children with type 1 diabetes. Pediatr Diabetes. 2018 12; 19(8):1451-1458. View Abstract
  7. Procedural Pain during Insertion of a Continuous Glucose Monitoring Device in Preterm Infants. J Pediatr. 2018 09; 200:261-264.e1. View Abstract
  8. Best Use of Models to Advance the Artificial Pancreas. Diabetes Technol Ther. 2018 03; 20(3):171-173. View Abstract
  9. Continuous Glucose Monitoring in Very Preterm Infants: A Randomized Controlled Trial. Pediatrics. 2017 Oct; 140(4). View Abstract
  10. Tight Glycemic Control in Critically Ill Children. N Engl J Med. 2017 02 23; 376(8):729-741. View Abstract
  11. Comment on Pinsker et al. Randomized Crossover Comparison of Personalized MPC and PID Control Algorithms for the Artificial Pancreas. Diabetes Care 2016;39:1135-1142. Diabetes Care. 2017 01; 40(1):e3. View Abstract
  12. Design and rationale of Heart and Lung Failure - Pediatric INsulin Titration Trial (HALF-PINT): A randomized clinical trial of tight glycemic control in hyperglycemic critically ill children. Contemp Clin Trials. 2017 02; 53:178-187. View Abstract
  13. Optimized Mealtime Insulin Dosing for Fat and Protein in Type 1 Diabetes: Application of a Model-Based Approach to Derive Insulin Doses for Open-Loop Diabetes Management. Diabetes Care. 2016 Sep; 39(9):1631-4. View Abstract
  14. Clinical Application of the Food Insulin Index for Mealtime Insulin Dosing in Adults with Type 1 Diabetes: A Randomized Controlled Trial. Diabetes Technol Ther. 2016 Apr; 18(4):218-25. View Abstract
  15. Bolus Estimation--Rethinking the Effect of Meal Fat Content. Diabetes Technol Ther. 2015 Dec; 17(12):860-6. View Abstract
  16. The artificial pancreas: evaluating risk of hypoglycaemia following errors that can be expected with prolonged at-home use. Diabet Med. 2016 Feb; 33(2):235-42. View Abstract
  17. Impact of fat, protein, and glycemic index on postprandial glucose control in type 1 diabetes: implications for intensive diabetes management in the continuous glucose monitoring era. Diabetes Care. 2015 Jun; 38(6):1008-15. View Abstract
  18. Tight glycemic control in the ICU - is the earth flat? Crit Care. 2014 Jun 27; 18(3):159. View Abstract
  19. Tight glycemic control after pediatric cardiac surgery in high-risk patient populations: a secondary analysis of the safe pediatric euglycemia after cardiac surgery trial. Circulation. 2014 Jun 03; 129(22):2297-304. View Abstract
  20. The authors reply. Pediatr Crit Care Med. 2014 Mar; 15(3):285-6. View Abstract
  21. Algorithms for a closed-loop artificial pancreas: the case for proportional-integral-derivative control. J Diabetes Sci Technol. 2013 Nov 01; 7(6):1621-31. View Abstract
  22. The artificial pancreas: is it important to understand how the ß cell controls blood glucose? J Diabetes Sci Technol. 2013 Sep 01; 7(5):1359-69. View Abstract
  23. Increasing use of hypertonic saline over mannitol in the treatment of symptomatic cerebral edema in pediatric diabetic ketoacidosis: an 11-year retrospective analysis of mortality*. Pediatr Crit Care Med. 2013 Sep; 14(7):694-700. View Abstract
  24. Cardiac output assessed by non-invasive monitoring is associated with ECG changes in children with critical asthma. J Clin Monit Comput. 2014 Feb; 28(1):75-82. View Abstract
  25. Design and rationale of safe pediatric euglycemia after cardiac surgery: a randomized controlled trial of tight glycemic control after pediatric cardiac surgery. Pediatr Crit Care Med. 2013 Feb; 14(2):148-56. View Abstract
  26. Dietary fat acutely increases glucose concentrations and insulin requirements in patients with type 1 diabetes: implications for carbohydrate-based bolus dose calculation and intensive diabetes management. Diabetes Care. 2013 Apr; 36(4):810-6. View Abstract
  27. Use of a food and drug administration-approved type 1 diabetes mellitus simulator to evaluate and optimize a proportional-integral-derivative controller. J Diabetes Sci Technol. 2012 Nov 01; 6(6):1401-12. View Abstract
  28. Cardiac parameters in children recovered from acute illness as measured by electrical cardiometry and comparisons to the literature. J Clin Monit Comput. 2013 Feb; 27(1):81-91. View Abstract
  29. Closed-loop insulin therapy improves glycemic control in children aged <7 years: a randomized controlled trial. Diabetes Care. 2013 Feb; 36(2):222-7. View Abstract
  30. Tight glycemic control versus standard care after pediatric cardiac surgery. N Engl J Med. 2012 Sep 27; 367(13):1208-19. View Abstract
  31. Changes in cardiac output and stroke volume as measured by non-invasive CO monitoring in infants with RSV bronchiolitis. J Clin Monit Comput. 2012 Jun; 26(3):197-205. View Abstract
  32. The identifiable virtual patient model: comparison of simulation and clinical closed-loop study results. J Diabetes Sci Technol. 2012 Mar 01; 6(2):371-9. View Abstract
  33. Value of continuous glucose monitoring for minimizing severe hypoglycemia during tight glycemic control. Pediatr Crit Care Med. 2011 Nov; 12(6):643-8. View Abstract
  34. Closed-loop insulin delivery utilizing pole placement to compensate for delays in subcutaneous insulin delivery. J Diabetes Sci Technol. 2011 Nov 01; 5(6):1342-51. View Abstract
  35. Cardiovascular effects of dexmedetomidine sedation in children. Anesth Analg. 2012 Jan; 114(1):193-9. View Abstract
  36. Non-invasive cardiac output and oxygen delivery measurement in an infant with critical anemia. J Clin Monit Comput. 2011 Apr; 25(2):113-9. View Abstract
  37. The effect of insulin feedback on closed loop glucose control. J Clin Endocrinol Metab. 2011 May; 96(5):1402-8. View Abstract
  38. Use of a continuous glucose sensor in an extracorporeal life support circuit. J Diabetes Sci Technol. 2011 Jan 01; 5(1):93-8. View Abstract
  39. Use of subcutaneous interstitial fluid glucose to estimate blood glucose: revisiting delay and sensor offset. J Diabetes Sci Technol. 2010 Sep 01; 4(5):1087-98. View Abstract
  40. Update on mathematical modeling research to support the development of automated insulin delivery systems. J Diabetes Sci Technol. 2010 May 01; 4(3):759-69. View Abstract
  41. Identification of intraday metabolic profiles during closed-loop glucose control in individuals with type 1 diabetes. J Diabetes Sci Technol. 2009 Sep 01; 3(5):1047-57. View Abstract
  42. Delays in minimally invasive continuous glucose monitoring devices: a review of current technology. J Diabetes Sci Technol. 2009 Sep 01; 3(5):1207-14. View Abstract
  43. Critical illness hyperglycemia: is failure of the beta-cell to meet extreme insulin demand indicative of dysfunction? Crit Care. 2009; 13(2):129. View Abstract
  44. 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 Apr; 11(4):207-10. View Abstract
  45. Mathematical modeling research to support the development of automated insulin-delivery systems. J Diabetes Sci Technol. 2009 Mar 01; 3(2):388-95. View Abstract
  46. Intensive Care Unit Insulin Delivery Algorithms: Why So Many? How to Choose? J Diabetes Sci Technol. 2009 Jan; 3(1):125-140. View Abstract
  47. Effect of age of infusion site and type of rapid-acting analog on pharmacodynamic parameters of insulin boluses in youth with type 1 diabetes receiving insulin pump therapy. Diabetes Care. 2009 Feb; 32(2):240-4. View Abstract
  48. Fully automated closed-loop insulin delivery versus semiautomated hybrid control in pediatric patients with type 1 diabetes using an artificial pancreas. Diabetes Care. 2008 May; 31(5):934-9. View Abstract
  49. Effect of puberty on the pharmacodynamic and pharmacokinetic properties of insulin pump therapy in youth with type 1 diabetes. Diabetes Care. 2008 Jan; 31(1):44-6. View Abstract
  50. Putative delays in interstitial fluid (ISF) glucose kinetics can be attributed to the glucose sensing systems used to measure them rather than the delay in ISF glucose itself. J Diabetes Sci Technol. 2007 Sep; 1(5):639-44. View Abstract
  51. Glucose control in pediatric intensive care unit patients using an insulin-glucose algorithm. Diabetes Technol Ther. 2007 Jun; 9(3):211-22. View Abstract
  52. Feasibility of automating insulin delivery for the treatment of type 1 diabetes. Diabetes. 2006 Dec; 55(12):3344-50. View Abstract
  53. Metabolic modelling and the closed-loop insulin delivery problem. Diabetes Res Clin Pract. 2006 Dec; 74 Suppl 2:S183-6. View Abstract
  54. Evaluation of the effect of gain on the meal response of an automated closed-loop insulin delivery system. Diabetes. 2006 Jul; 55(7):1995-2000. View Abstract
  55. Interstitial fluid glucose dynamics during insulin-induced hypoglycaemia. Diabetologia. 2005 Sep; 48(9):1833-40. View Abstract
  56. Closed-loop insulin delivery - what lies between where we are and where we are going? Expert Opin Drug Deliv. 2005 Mar; 2(2):353-62. View Abstract
  57. Modeling insulin action for development of a closed-loop artificial pancreas. Diabetes Technol Ther. 2005 Feb; 7(1):94-108. View Abstract
  58. 40th EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004. Diabetologia. 2004 Aug; 47(Suppl 1):A1-A464. View Abstract
  59. Evaluation of insulin sensitivity and beta-cell function indexes obtained from minimal model analysis of a meal tolerance test. Diabetes. 2004 May; 53(5):1201-7. View Abstract
  60. Closed-loop insulin delivery-the path to physiological glucose control. Adv Drug Deliv Rev. 2004 Feb 10; 56(2):125-44. View Abstract
  61. Determination of plasma glucose during rapid glucose excursions with a subcutaneous glucose sensor. Diabetes Technol Ther. 2003; 5(1):27-31. View Abstract
  62. The role of the independent variable to glucose sensor calibration. Diabetes Technol Ther. 2003; 5(3):401-10. View Abstract
  63. Modeling beta-cell insulin secretion--implications for closed-loop glucose homeostasis. Diabetes Technol Ther. 2003; 5(6):953-64. View Abstract
  64. High glucose stimulates early response gene c-Myc expression in rat pancreatic beta cells. J Biol Chem. 2001 Sep 21; 276(38):35375-81. View Abstract
  65. Adaptation of beta-cell mass to substrate oversupply: enhanced function with normal gene expression. Am J Physiol Endocrinol Metab. 2001 May; 280(5):E788-96. View Abstract
  66. Gene expression of VEGF and its receptors Flk-1/KDR and Flt-1 in cultured and transplanted rat islets. Transplantation. 2001 Apr 15; 71(7):924-35. View Abstract
  67. Potential role of the early response gene c-myc in beta-cell adaptation to changes in glucose concentration. Diabetes. 2001 Feb; 50 Suppl 1:S137. View Abstract
  68. Islets in alginate macrobeads reverse diabetes despite minimal acute insulin secretory responses. Transplantation. 2001 Jan 27; 71(2):203-11. View Abstract
  69. Beta-cell dysfunction in 48-hour glucose-infused rats is not a consequence of elevated plasma lipid or islet triglyceride levels. Metabolism. 2000 Jun; 49(6):755-9. View Abstract
  70. Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor. Cell Transplant. 2000 Jan-Feb; 9(1):115-24. View Abstract
  71. Can interstitial glucose assessment replace blood glucose measurements? Diabetes Technol Ther. 2000; 2(3):461-72. View Abstract
  72. Subcutaneous glucose predicts plasma glucose independent of insulin: implications for continuous monitoring. Am J Physiol. 1999 09; 277(3):E561-71. View Abstract
  73. Role of portal insulin delivery in the disappearance of intravenous glucose and assessment of insulin sensitivity. Diabetes. 1998 May; 47(5):714-20. View Abstract
  74. Physiological insulinemia acutely modulates plasma leptin. Diabetes. 1998 Apr; 47(4):544-9. View Abstract
  75. Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity. J Clin Endocrinol Metab. 1998 Feb; 83(2):453-9. View Abstract
  76. Critical evaluation of the combined model approach for estimation of prehepatic insulin secretion. Am J Physiol. 1998 01; 274(1):E172-83. View Abstract
  77. Indirect effect of insulin to suppress endogenous glucose production is dominant, even with hyperglucagonemia. J Clin Invest. 1997 Dec 15; 100(12):3121-30. View Abstract
  78. Method of insulin administration has no effect on insulin sensitivity estimates from the insulin-modified minimal model protocol. Diabetes. 1997 Dec; 46(12):2044-8. View Abstract
  79. Differences between the tolbutamide-boosted and the insulin-modified minimal model protocols. Diabetes. 1997 Jul; 46(7):1167-71. View Abstract
  80. Extracellular glucose distribution is not altered by insulin: analysis of plasma and interstitial L-glucose kinetics. Am J Physiol. 1996 Nov; 271(5 Pt 1):E855-64. View Abstract
  81. Toward an integrated phenotype in pre-NIDDM. Diabet Med. 1996 Sep; 13(9 Suppl 6):S67-77. View Abstract
  82. Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs. J Clin Invest. 1996 Aug 01; 98(3):741-9. View Abstract
  83. Transendothelial insulin transport is not saturable in vivo. No evidence for a receptor-mediated process. J Clin Invest. 1996 Mar 15; 97(6):1497-503. View Abstract
  84. Free fatty acid as a link in the regulation of hepatic glucose output by peripheral insulin. Diabetes. 1995 Sep; 44(9):1038-45. View Abstract
  85. Insulin sensitivity accounts for glucose and lactate kinetics after intravenous glucose injection. Diabetes. 1995 Aug; 44(8):954-62. View Abstract
  86. Assessment of extracellular glucose distribution and glucose transport activity in conscious rats. Am J Physiol. 1995 Apr; 268(4 Pt 1):E712-21. View Abstract
  87. OOPSEG: a data smoothing program for quantitation and isolation of random measurement error. Comput Methods Programs Biomed. 1995 Jan; 46(1):67-77. View Abstract
  88. Repeatability of insulin sensitivity and glucose effectiveness from the minimal model. Implications for study design. Diabetes. 1994 Nov; 43(11):1365-71. View Abstract
  89. Dynamics of glucose production and uptake are more closely related to insulin in hindlimb lymph than in thoracic duct lymph. Diabetes. 1994 Feb; 43(2):180-90. View Abstract
  90. Quantitation of measurement error with Optimal Segments: basis for adaptive time course smoothing. Am J Physiol. 1993 Jun; 264(6 Pt 1):E902-11. View Abstract
  91. Thoracic duct lymph. Relative contribution from splanchnic and muscle tissue. Diabetes. 1993 May; 42(5):720-31. View Abstract
  92. Reduced sample number for calculation of insulin sensitivity and glucose effectiveness from the minimal model. Suitability for use in population studies. Diabetes. 1993 Feb; 42(2):250-6. View Abstract
  93. Modeling of insulin action in vivo. Annu Rev Physiol. 1992; 54:861-83. View Abstract
  94. Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate compartment in dogs. Quantitative aspects and implications for transport. J Clin Invest. 1991 Oct; 88(4):1272-81. View Abstract
  95. Underlying neural computations for some visual phenomena. Biol Cybern. 1988; 60(2):89-106. View Abstract
  96. On the identification of neural responses. Biol Cybern. 1987; 56(2-3):97-106. View Abstract
  97. Control mechanisms of a neural network. Biol Cybern. 1986; 54(1):21-8. View Abstract
  98. Control properties of perceptual transient and sustained mechanisms. Biol Cybern. 1985; 52(3):177-86. View Abstract

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