Generation of Virtual Patient Populations That Represent Real Type 1 Diabetes Cohorts

• Main Authors: Sayyar Ahmad, Charrise M. Ramkissoon, Aleix Beneyto, Ignacio Conget, Marga Giménez, Josep Vehi
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Mathematics
• Subjects: type 1 diabetes; virtual patients; type 1 diabetes simulator; artificial pancreas
• Online Access: https://www.mdpi.com/2227-7390/9/11/1200

Preclinical testing and validation of therapeutic strategies developed for patients with type 1 diabetes (T1D) require a cohort of virtual patients (VPs). However, current simulators provide a limited number of VPs, lack real-life scenarios, and inadequately represent intra- and inter-day variability in insulin sensitivity and blood glucose (BG) profile. The generation of a realistic scenario was achieved by using the meal patterns, insulin profiles (basal and bolus), and exercise sessions estimated as disturbances using clinical data from a cohort of 14 T1D patients using the Medtronic 640G insulin pump provided by the Hospital Clínic de Barcelona. The UVa/Padova’s cohort of adult patients was used for the generation of a new cohort of VPs. Insulin model parameters were optimized and adjusted in a day-by-day fashion to replicate the clinical data to create a cohort of 75 VPs. All primary and secondary outcomes reflecting the BG profile of a T1D patient were analyzed and compared to the clinical data. The mean BG 166.3 versus 162.2 mg/dL (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>p</mi></semantics></math></inline-formula> = 0.19), coefficient of variation 32% versus 33% (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>p</mi></semantics></math></inline-formula> = 0.54), and percent of time in range (70 to 180 mg/dL) 59.6% versus 66.8% (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>p</mi></semantics></math></inline-formula> = 0.35) were achieved. The proposed methodology for generating a cohort of VPs is capable of mimicking the BG metrics of a real cohort of T1D patients from the Hospital Clínic de Barcelona. It can adopt the inter-day variations in the BG profile, similar to the observed clinical data, and thus provide a benchmark for preclinical testing of control techniques and therapy strategies for T1D patients.