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.
Thabit H, Tauschmann M, Allen JM, Leelarathna L, Hartness S, Wilinska ME, Acerini CL, Dellweg S, Benesch C, Heinemann L, Mader JK, Holzer M, Kojzar H, Exall J, Yong J, Pichierri J, Barnard KD, Kollman C, Cheng P, Hidmarsh PC, Campbell FM, Arnolds S, Pieber TR, Evans ML, Dunger DB, Hovorka R; APCam Consortium; AP@home Consortium. (2015). Home Use of an Artificial Beta Cell in Type 1 Diabetes. N Engl J Med 2015 Nov 26;373(22):2129-40. doi: 10.1056/NEJMoa1509351. Epub 2015 Sep 17. PMID: 26379095.
Thabit H, Lunina-Solomon A, Stadler M, Leelarathna L, Walkinshaw E, Pernet A, Allen JM, Iqbal A, Choudhary P, Kumareswaran K, Nodale M, Nisbet C, Wilinksa ME, Barnard KD, Dunger DB, Heller SR, Amiel SA, Evans ML, Hovorka R. (2014). Home use of closed-loop insulin delivery for overnight glucose control in adults with type 1 diabetes: a 4-week, multicentre, randomised crossover study. Lancet Diabetes Endocrinol. 2014 Sep;2(9):701-9. doi: 10.1016/S2213-8587(14)70114-7. Epub 2014 Jun 16. PMID: 24943065. PMCID: PMC4165604.
Leelarathna L, Dellweg S, Mader JK, Allen JM, Benesh C, Doll W, Ellmerer M, Hartnell S, Heinemann L, Kojzar H, Michalweski L, Nodale M, Thabit H, Wilinska ME, Pieber TR, Arnolds S, Evans ML, Hovorka R; AP@home Consotium. (2014). Day and night home closed-loop insulin delivery in adults with type 1 diabetes: three-center randomized crossover study. Diabetes Care. 2014 Jul;37(7):1931-7. doi: 10.2337/dc13-2911. PMID: 24963110.
Hovorka R, Elleri D, Thabit H, Allen JM, Leelarathna L, El-Khairi R, Kumareswaran K, Caldwell K, Calhoun P, Kollman C, Murphy HR, Acerini CL, Wilinska ME, Noldale M, Dunger DB. (2014). Overnight closed-loop insulin delivery in young people with type 1 diabetes: a free-living, randomized clinical trial. Diabetes Care. 2014;37(5):1204-11. doi: 10.2337/dc13-2644. PMID: 24757227. PMCID: PMC3994941.
Leelarathna L, English SW, Thabit H, Caldwell K, Allen JM, Kumareswaran K, Wilinska ME, Nodale M, Mangat J, Evans ML, Burnstein R, Hovorak R. (2013). Feasibility of fully automated closed-loop glucose control using continuous subcutaneous glucose measurements in critical illness: a randomized controlled trial. Crit Care. 2013 Jul 24;17(4):R159. doi: 10.1186/cc12838. PMID: 23883613. PMCID: PMC4056260.