A modified minimal model analysis of insulin sensitivity and glucose-mediated glucose disposal in insulin-dependent diabetes

Abstract

Although glucose utilization is impaired in insulin-dependent diabetes mellitus (IDDM), it is unclear whether this is due to reductions in insulin sensitivity (S I) and/or glucose-mediated glucose disposal (S G). The minimal model of Bergman et al can be applied to a frequently sampled intravenous glucose tolerance test (FSIGT) to simultaneously estimate S I and S G, but cannot accommodate data from diabetics. Exogenous insulin approximating the normal pattern of insulin secretion was infused during FSIGTs in eight young non-obese C-peptide-negative IDDM subjects, but with the total dose modified to achieve sufficient glucose disappearance rates (K G) to allow analysis of data. The minimal model was modified to model the effects of the exogenous insulin on glucose kinetics to estimate S I and S G. Despite deliberately achieving supranormal plasma-free insulin levels during the FSIGT (“first-phase insulin” = 62 ± 9 SE mU/L; “second phase insulin” = 34 ± 9 mU/L), the diabetics showed low-normal K G values (1.3 ± 0.29 min −1 × 10 2). Using the model, good parameter resolution (fractional SD [FSD] < .5) was achieved (IDDM v controls: S I = 2.5 ± 0.6 v 8.3 ± 1.5 min −1 · mU −1 · L −1 × 10 4; SG = 1.6 ± 0.5 v 2.6 ± 0.2 min −1 × 10 2; P < .05). This reduction in S G was confirmed in the same IDDM subjects by FSIGT during basal insulin infusion only (S G = 1.0 ± 0.3 min −1 × 10 2). The reduction in S I was confirmed by our previous euglycemic clamp studies in a similar IDDM group, where S I = 4.2 ± 1.0 min −1 · mU −1 · L −1. It is feasible to use this modification of the Bergman minimal model to perform a simultaneous estimation of S I and S G in IDDM. Reductions in both S I and S G contribute to the impairment of glucose utilization seen in IDDM subjects treated by standard insulin regimens.