Document Detail

Simple modeling allows prediction of steady-state glucose disposal rate from early data in hyperinsulinemic glucose clamps.
MedLine Citation:
PMID:  19920219     Owner:  NLM     Status:  MEDLINE    
After a constant insulin infusion is initiated, determination of steady-state conditions for glucose infusion rates (GIR) typically requires >or=3 h. The glucose infusion follows a simple time-dependent rise, reaching a plateau at steady state. We hypothesized that nonlinear fitting of abbreviated data sets consisting of only the early portion of the clamp study can provide accurate estimates of steady-state GIR. Data sets from two independent laboratories were used to develop and validate this approach. Accuracy of the predicted steady-state GDR was assessed using regression analysis and Altman-Bland plots, and precision was compared by applying a calibration model. In the development data set (n = 88 glucose clamp studies), fitting the full data set with a simple monoexponential model predicted reference GDR values with good accuracy (difference between the 2 methods -0.37 mg x kg(-1) x min(-1)) and precision [root mean square error (RMSE) = 1.11], validating the modeling procedure. Fitting data from the first 180 or 120 min predicted final GDRs with comparable accuracy but with progressively reduced precision [fitGDR-180 RMSE = 1.27 (P = NS vs. fitGDR-full); fitGDR-120 RMSE = 1.56 (P < 0.001)]. Similar results were obtained with the validation data set (n = 183 glucose clamp studies), confirming the generalizability of this approach. The modeling approach also derives kinetic parameters that are not available from standard approaches to clamp data analysis. We conclude that fitting a monoexponential curve to abbreviated clamp data produces steady-state GDR values that accurately predict the GDR values obtained from the full data sets, albeit with reduced precision. This approach may help reduce the resources required for undertaking clamp studies.
Pooja Singal; Ranganath Muniyappa; Robin Chisholm; Gail Hall; Hui Chen; Michael J Quon; Kieren J Mather
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Publication Detail:
Type:  Comparative Study; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Validation Studies     Date:  2009-11-17
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  298     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-08-17     Completed Date:  2010-09-01     Revised Date:  2011-07-22    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E229-36     Citation Subset:  IM    
Indiana University School of Medicine, Indianapolis, USA.
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MeSH Terms
Analysis of Variance
Blood Glucose / metabolism*
Dose-Response Relationship, Drug
Glucose Clamp Technique / methods*
Hyperinsulinism / chemically induced,  metabolism*
Infusions, Intravenous
Insulin / administration & dosage,  blood*
Middle Aged
Models, Biological*
Predictive Value of Tests
Reproducibility of Results
Time Factors
Young Adult
Grant Support
Reg. No./Substance:
0/Blood Glucose; 11061-68-0/Insulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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