Transient and steady-state euglycemic clamp validation of a model for glycemic control and insulin sensitivity testing.
BACKGROUND
There is an urgent need for a simple and accurate measure of insulin sensitivity to diagnose insulin resistance in the general population and quantify changes due to clinical intervention. A new physiological control model of glucose and insulin metabolism is validated with the euglycemic-hyperinsulinemic clamp during steady and transient states.


METHODS
The data consist of n = 60 (15 lean, 15 overweight, 15 obese, and 15 morbidly obese) euglycemic-hyperinsulinemic clamp trials performed on normoglycemic insulin-resistant individuals. The glucose and insulin model is fitted using an integral-based method. Correlations between clamp-derived insulin sensitivity index (ISI) and the model's insulin sensitivity parameter (SI) are obtained during steady and transient states. Results are compared with log-homeostasis model assessment (HOMA), a widely used fasting surrogate for insulin sensitivity.


RESULTS
Correlation between model-based insulin sensitivity, SI, and ISIG (ISI normalized by steady-state glucose) is r = 0.99 (n = 60) at steady state and r = 0.97 at transient state, respectively. Correlations did not significantly change across subgroups, with narrow 95% confidence intervals. Log-HOMA correlations are r=-0.72 to SI and r=-0.71 to ISIG for the overall population but are significantly lower in the subgroups, with wide 95% confidence intervals.


CONCLUSIONS
The model-based insulin sensitivity parameter, SI, highly correlates to ISIG in all subgroups, even when only considering a transient state. The high correlation of SI offers the potential for a short, simple yet highly correlated, model-based assessment of insulin sensitivity that is not currently available.
Lotz
Thomas F
TF
Department of Mechanical Engineering, Centre for Bioengineering, University of Canterbury, Christchurch, New Zealand.
Chase
J Geoffrey
JG
McAuley
Kirsten A
KA
Lee
Dominic S
DS
Lin
Jessica
J
Hann
Christopher E
CE
Mann
Jim I
JI
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D005215:Fasting; D015309:Glucose Clamp Technique / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D009767:Obesity, Morbid / Q000097:blood; D050177:Overweight; D015203:Reproducibility of Results
D001786:Blood Glucose; D007328:Insulin