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A minimal model of glucose absorption, production and disappearance for double-tracer oral glucose tolerance tests

Thomaseth K;Gastaldelli A
2007
2007
Istituto di Elettronica e di Ingegneria dell'Informazione e delle Telecomunicazioni - IEIIT
Istituto di Fisiologia Clinica - IFC
INGEGNERIA BIOMEDICA
Annual Meeting of American Diabetes Association
56
A406
1
22-26 giugno 2007
Chicago
model of glucose absorption
ogtt
Assessment of glucose absorption (GA), endogenous production (EGP) and disposal (GD) during OGTT requires co-administration of multiple-traced glucose via oral and iv routes as well as complex numerical data analysis. GA and EGP are commonly described by piecewise polynomials, which makes identification of covariates influencing these processes difficult. To overcome this problem, we propose a new mathematical modeling approach that expresses with simple parametric functions GA, EGP and GD, accounting also for effective hepatic and peripheral insulin. A population parameter estimation approach provided individual and average kinetic parameters as well as significant covariates (e.g. diabetes, BMI) that predict between-subject variability. Twelve type 2 diabetic patients (D) (5F/7M, age = 53.6±2.5 yrs, BW = 81.9±3.6 kg, BMI= 30.5±1.1 kg m-2) and 10 normal glucose tolerant subjects (N) matched for BMI (5F/5M, age = 39.6±3.7, BW = 90.1±3.9, BMI = 31.1±0.9), received after overnight fast a primed-continuous infusion of 0.25 µCi/min [3-3H]-glucose and, after equilibration at T=0, a 75 g glucose OGTT with 75 µCi [1-14C]-glucose added. Blood was sampled every 15 min between -30 and 240 min for measuring glucose and insulin. Insulin-independent glucose clearance was on average 0.72 dl/min (±14% CV) and not correlated with any covariate; insulin sensitivity of glucose disappearance in N was 0.088 dl/min/(µU/ml) (±19%) about 3 times that in D: 0.030 (±20%); 50% inhibition of EGP was found at a small supra-basal insulin level 5.6 µU/ml (±28%) which increased significantly with BMI +26%/(kg/m2) (±8%) but not with diabetes. In addition to confirmatory findings and the new hypothesis about the dominant role of BMI on EGP, the presented population model characterizes in single individuals glucose kinetics from double-tracer OGTT and predicts the influence of covariates, which will allow the design of simplified experiments for routine use.
2
info:eu-repo/semantics/conferenceObject
none
274
04 Contributo in convegno::04.02 Abstract in Atti di convegno
Thomaseth K.; Pavan A.; Berria R.; Glass L.; Defronzo R. A.; Gastaldelli A.
04.02 Abstract in Atti di convegno
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/145435
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