Director of Research
Department of Paediatrics
Mathematical modeling to support diagnosis and treatment of metabolic diseases
Our aim is to support the diagnosis and treatment of metabolic diseases using mathematical modeling techniques with particular focus on diabetes. We use existing and develop new methods to quantify insulin sensitivity, insulin secretion, and metabolic fluxes under steady and non-steady state conditions with deterministic and stochastic modeling techniques. Our interest extends to developing in silico populations to inform and complement clinical trialing.
We are developing and testing a prototype of artificial pancreas in collaboration with Professor Dunger and Dr Acerini (Paediatrics). The artificial pancreas consists of a subcutaneous glucose monitor, a control algorithm, and an insulin pump and has the potential to revolutionize the treatment of subjects with type 1 diabetes as short- and midterm availability of other closed-loop control options is unlikely. The work includes the development of a computer-based simulation environment, where we will evaluate and optimise the system performance prior to clinical investigations. We are developing in silico population of children and adolescents treated by insulin with an appropriate representation of between and within subject variability.
We are also interested in insulin titration in critically ill subjects. Our control algorithm is being tested in four intensive care units across Europe and a collaboration with medical devices company has been secured to explore commercial exploitation. We have also developed an in silico population of critically ill subjects at surgical and medical ICU to test glucose controllers.
Elleri D, Allen JM, Harris J, Kumareswaran K, Nodale M, Leelarathna L, Acerini CL, Haidar A, Wilinska ME, Jackson N, Umpleby AM, Evans ML, Dunger DB. Hovorka R. (2013). Absorption patterns of meals containing complex carbohydrates in type 1 diabetes. Diabetologia, 2013 Feb 23. [Epub ahead of print]. PMID:23435829.
Leelarathna L, Nodale M, Allen JM, Elleri D, Kumareswaran K, Haidar A, Caldwell K, Wilinska ME, Acerini CL, Evans ML, Murphy HR, Dunger DB, Hovorka R. (2013). Evaluating the accuracy and large inaccuracy of two continuous glucose monitoring systems. Diabetes Technol Ther. 2013 Feb; 15(2):143-9. doi: 10.1089/dia.2012.0245. Epub 2012 Dec 20. PMID:23256605. PMCID: PMC3558677 .
Elleri D, Allen JM, Kumareswaran K, Leelarathna L, Nodale M, Caldwell K, Cheng P, Kollman C, Haidar A, Murphy HR, Wilinska ME, Acerini CL, Dunger DB, Hovorka R. (2012). Closed-Loop Basal Insulin Delivery Over 36 Hours in Adolescents With Type 1 Diabetes: Randomized clinical trial. Diabetes Care, 2012 Nov 27. [Epud ahead of print]. PMID:23193217.
Elleri D, Allen JM, Biagioni M, Kumareswaran K, Leelarathna L, Caldwell K, Nodale M, Wilinska ME, Acerini CL, Dunger DB, Hovorka R. (2012). Evaluation of a portable ambulatory prototype for automated overnight closed-loop insulin delivery in young people with type 1 diabetes.Pediatr Diabetes, 2012 Sep;13(6):449-53. doi: 10.1111/j.1399-5448.2012.00903.x. Epub 2012 Jul 23. PMID: 22817340.
Haidar A, Elleri D, Allen JM, Harris J, Kumareswaran K, Nodale M, Acerini CL, Wilinksa ME, Jackson N, Umpleby AM, Evans ML, Dunger DB, Hovorka R. (2012). Validity of triple-and dual-tracer techniques to estimate glucose appearance. Am J Physiol Endocrinol Metab. 2012 Jun 15;302(12):E1493-501. doi: 10.1152/ajpendo.00581.2011. Epub 2012 Mar 27. PMID: 22454288. PMCID: PMC3378162.
Murphy HR, Elleri D, Allen JM, Harris J, Simmons D, Rayman G, Temple RC, Umpleby AM, Dunger DB, Haidar A, Nodale M, Wilinska ME, Hovorka R. (2012). Pathophysiology of postprandial hyperglycaemia in women with type 1 diabtes during pregnancy. Diabetologia, 55(2):282-93. PMID: 22080230.
Murphy HR, Kumareswaran K, Elleri D, Allen JM, Caldwell K, Biagioni M, Simmons D, Dunger DB, Nodale M, Wilinska ME, Amiel SA, Hovorka R. (2011). Safety and efficacy of 24-h closed-loop insulin delivery in well-controleed pregnany women with type 1 diabetes: a randomized crossover case series. Diabetes Care, 34(12):2527-9. PMID: 22011408. PMCID: PMC3220861.
Lunn DJ, Wei C, Hovorka R. (2011). Fitting dynamic models with forcing function: application to continuous glucose monitoring in insulin therapy. Stat Med, 30(18):2234-50. PMID: 21590789. PMCID: PMC3201840.
Elleri D, Dunger DB, Hovorka R. (2011). Closed-loop insulin delivery for treatment of type 1 diabetes. BMC Med, 2011 Nov 9;9:120. PMID: 22071283. PMCID: PMC3229449.
Hovorka R.(2011). Closed-loop insulin delivery: from bench to clinical practice. Nat Rev Endocrinol, 7(7):385-95. PMID: 21343892.
Hovorka R, Kumareswaran K, Harris J, Elleri D, Xing D, Kollman C, Nodale M, Murphy HR, Dunger DB, Amiel SA, Heller SR, Wilinska ME, Evans ML. (2011). Overnight closed loop insulin delivery (artificial pancreas) in adults with type 1 diabetes: crossover randomised controlled studies. BMJ, 342:d1855. doi: 10.1136/bmj.d1855. PMID: 21493665. PMCID: PMC3077739.
Murphy HR, Elleri D, Allen JM, Harris J, Simmons D, Rayman G, Temple R, Dunger DB, Haidar A, Nodale M, Wilinska ME, Hovorka R. (2011). Closed-loop insulin delivery during pregnancy complicated by type 1 diabetes. Diabetes Care, 34(2):406-11. PMID: 21216859. PMCID: PMC3024358.
Hovorka R, Allen JM, Elleri D, Chassin LJ, Harris J, Xing D, Kollman C, Hovorka T, Larsen AM, Nodale M, De Palma A, Wilkinska ME, Acerini CL, Dunger DB. (2010). Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet, 375(9716):743-51. PMID: 20138357.
Wilinska ME, Chassin LJ, Acerini CL, Allen JM, Dunger DB, Hovorka R. (2010). Stimulation environment to evaluate closed-loop insulin delivery systems in type 1 diabetes. J Diabetes Sci Technol, 4(1):132-44. PMID: 20167177. PMCID: PMC2825634.