Andreas Groth & Mikael Thomsen
Technical University of Denmark & Novo Nordisk A/S
Objectives: Evaluating the correspondence between insulin PD measurements by glucose clamps and IVGTT-based insulin-glucose models.
Methods: We compared two recent IVGTT-based models: Hovorka et al., AJPEndo 282(5) (M1) vs. DeGaetano/Arino, JMathBiol 40 (M2) with respect to predictions about insulin PD measurement feasibility.
Results: By model structure, M1 predicts that insulin PD effects may be measured with acceptable accuracy by maintaining a realistic control of glucose levels in glucose clamps. M2 predicts that parameter values for each subject determine whether sensitivity to insulin is sufficiently high compared to glucose sensitivity. Assuming 300 pM insulin, the table shows for each M1 subject the relevant reported parameter values followed by our results: The predicted signal-to-noise ratio when measuring insulin PD (+/- 5% glucose is a realistic “noise” level in a glucose clamp). If a 100% difference in insulin level is predicted to elicit less effect on the measured PD than 5% noise on the glucose level, we deem insulin PD measurement predicted non-feasible in that subject.
Conclusion: Two recently proposed models of insulin action and glucose metabolism in healthy subjects during IVGTT provide very different predictions about achievable accuracy of insulin PD measurements: With the reported parameter values, M2 predicts that accidental small differences in experimental glucose levels may obscure insulin PD measurements in 70% of the subjects studied vs. 0% for M1.
| Subject | Glucose effectiveness b1 min-1 | Insulin sensitivity b4 pM-1 min-1 | Assumed insulin level pM | % increase in insulin level (signal) required to elicit same effect on glucose disposal as 5% increase in glucose level (noise) | Insulin PD measurement realistically feasible in subject? |
| 1 | 0.0226 | 3.80E-08 | 300 | 9917 | No |
| 2 | 0.0509 | 1.29E-07 | 300 | 6581 | No |
| 3 | 0.0309 | 6.99E-07 | 300 | 742 | No |
| 4 | 0.0084 | 7.55E-05 | 300 | 6.9 | Yes |
| 5 | 0.0273 | 1.10E-07 | 300 | 4141 | No |
| 6 | 0.0002 | 1.09E-04 | 300 | 5.0 | Yes |
| 7 | 0.0001 | 3.73E-04 | 300 | 5.0 | Yes |
| 8 | 0.0565 | 5.70E-06 | 300 | 170 | No |
| 9 | 0.0135 | 3.51E-08 | 300 | 6415 | No |
| 10 | 0.0159 | 8.72E-08 | 300 | 3044 | No |
Reference: PAGE 12 (2003) Abstr 366 [www.page-meeting.org/?abstract=366]
Poster: poster