Quantificazione del ruolo svolto dai principali fattori determinanti la glicemia durante un pasto misto, nei pazienti affetti da diabete mellito tipo 1 in terapia con microinfusore insulinico associato a glucosensore

Title: Quantitation of the roles played by the main determinants of meal glucose tolerance in patients with type 1 diabetes on sensor-augmented insulin-pump therapy. Background. Glucose sensor augmented insulin pump therapy (SAP), in which patients wear both a pump for subcutaneous insulin delivery (CSII) and a subcutaneously installed glucose sensor for continuous glucose monitoring (CGM) is nowadays the gold standard but not yet the optimal treatment of type 1 diabetes (T1DM). The relative roles of each component of the glucose (G)/ insulin (I) system in determining post-meal hyperglycaemia in T1DM are still under debate. The use of Metabolic Control Analysis (MCA) allows to compute the coefficients of control of plasma glucose (CCG), which quantify the control exerted by each component of the G/I system on glucose concentration. Aim. Aim of this research was to quantify the CCG of the main components of the G/I system during the mixed meal test (MMT). Materials and Methods. 10 T1DM patients (7 males and 3 females; age: 39.8 ± 3.9 years; BMI 23.3 ± 0.7 Kg/m2; HbA1c 7.8 ± 0.2%) on insulin pump and continuous glucose monitoring (CGM) participated in two studies: 1. Euglycemic Insulin (240 pmol/min/m2 BSA) clamp (duration: 120 minutes, M value 1091 ± 133 pmol/min/m2 BSA); 2. MMT (292 Cal; 38.9 g complex CHO, 8.9 g lipids and 14 g proteins) with plasma insulin, plasma glucose and interstitial glucose assessment for 360 minutes. With our modelling strategy, data from both clamp and MMT are used to build an in silico replica (“virtual patients”) of the G/I system of each patient, which behaves as the real patient during the MMT. Virtual patients were used to compute the CCG of plasma glucose. Results. During the MMT, plasma glucose and insulin started from 10.7 ± 1.3 mM and 68.8 ± 7.7 pM and peaked at 12.7 ± 1.1 mM (time: +90’) and at 150 ± 15 pM (time: + 60’) respectively. The CCG of key components of the G/I system were calculated. The insulin mean transit time across subcutaneous tissue had the highest CCG among all. The CCG of the meal carbohydrates (CHO) content was remarkable during the whole time of the MMT (p<0.001). The CCG of CHO transit time across the gut was noticeable in the first half and became negligible in the second half of the MMT (p<0.01). Conclusions. In patients with T1DM on SAP therapy, the insulin mean transit time across subcutaneous tissue was a primary determinant of plasma glucose in some patients, after a MMT. The meal CHO content was also remarkable in determining post-meal hyperglycaemia in T1DM. These findings may have important implications for the development and the refinement of closed loop control of subcutaneous insulin delivery systems.