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We have separated the effect of insulin on glucose distribution/transport, glucose disposal, and endogenous production (EGP) during an intravenous glucose tolerance test (IVGTT) by use of a dual-tracer dilution methodology. Six healthy lean male subjects (age 33 [+ or -] 3 yr, body mass index 22.7 [+ or -] 0.6 kg/[m.sup.2]) underwent a 4-h IVGTT (0.3 g/kg glucose enriched with 3-6% D-[[U-.sup.13]C]glucose and 5-10% 3-O-methyl-D-glucose) preceded by a 2-h investigation under basal conditions (5 mg/kg of D-[[U.sup.-13]C]glucose and 8 mg/kg of 3-O-methyl-D-glucose). A new model described the kinetics of the two glucose tracers and native glucose with the use of a two-compartment structure for glucose and a one-compartment structure for insulin effects. Insulin sensitivities of distribution/transport, disposal, and EGP were similar (11.5 [+ or -] 3.8 vs. 10.4 [+ or -] 3.9 vs. 11.1 [+ or -] 2.7 x [10.sup.-2] ml * [kg.sup.-1] * [min.sup.-1] per mU/l; P = nonsignificant, ANOVA). When expressed in terms of ability to lower glucose concentration, stimulation of disposal and stimulation of distribution/transport accounted each independently for 25 and 30%, respectively, of the overall effect. Suppression of EGP was more effective (P < 0.01, ANOVA) and accounted for 50% of the overall effect. EGP was suppressed by 70% (52-82%) (95% confidence interval relative to basal) within 60 min of the IVGTT; glucose distribution/ transport was least responsive to insulin and was maximally activated by 62% (34-96%) above basal at 80 min compared with maximum 279% (116-565%) activation of glucose disposal at 20 min. The deactivation of glucose distribution/transport was slower than that of glucose disposal and EGP (P < 0.02) with half-times of 207 (84-510), 12 (7-22), and 29 (16-54) min, respectively. The minimal-model insulin sensitivity was tightly correlated with and linearly related to sensitivity of EGP (r = 0.96, P < 0.005) and correlated positively but nonsignificantly with distribution/transport sensitivity (r = 0.73, P = 0.10) and disposal sensitivity (r = 0.55, P = 0.26). We conclude that, in healthy subjects during an IVGTT, the two peripheral insulin effects account jointly for approximately one-half of the overall insulin-stimulated glucose lowering, each effect contributing equally. Suppression of EGP matches the effect in the periphery. glucose kinetics; compartment modeling; D-[[U.sup.-13]C]glucose; 3-O-methyl-D-glucose; insulin action; glucose transport; glucose disposal; endogenous glucose production; intravenous glucose tolerance test

Diabetes advisory system (DIAS) is a decision support system, which has been developed to provide advice on the amount of insulin injected by subjects with insulin-dependent diabetes mellitus (IDDM). DIAS employs a temporal causal probabilistic network (CPN) to implement a stochastic model of carbohydrate metabolism. The CPN network has recently been extended to provide also advice to subjects with noninsulin-dependent diabetes mellitus (NIDDM). However, due to increased complexity and size of the extended CPN the calculations became unfeasible. The CPN network was, therefore, simplified and a novel approach employed to generate conditional probability tables. The principles of dynamic CPN's were adopted and, in combination with the method of conditioning, learning, and forecasting, were implemented in a time- and memory-efficient way. An evaluation using experimental data was carried out to compare the original and revised DIAS implementations employing data collected by patients with IDDM, and to assess the a posteriori identifiability of model parameters in patients with NIDDM. Index Terms - Bayesian networks, carbohydrate metabolism, causal probabilistic networks, diabetes, dynamic causal probabilistic networks, stochastic modeling.