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Am J Physiol Endocrinol Metab (September 16, 2008). doi:10.1152/ajpendo.90207.2008
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Submitted on February 4, 2008
Revised on September 4, 2008
Accepted on September 15, 2008

VALIDATION OF SIMPLE INDEXES TO ASSESS INSULIN SENSITIVITY DURING PREGNANCY IN WISTAR AND SPRAGUE DAWLEY RATS

Judith Cacho1, Julio Sevillano1, Javier de Castro1, Emilio Herrera2, and Maria del Pilar Ramos1*

1 University CEU San Pablo
2 Universidad San Pablo-CEU

* To whom correspondence should be addressed. E-mail: pramos{at}ceu.es.

Insulin resistance plays a role in the pathogenesis of diabetes, including gestational diabetes. The glucose-clamp is considered the gold standard for determining in vivo insulin sensitivity, both in human and in animal models. However, the clamp is laborious, time consuming and, in animals, requires anesthesia and collection of multiple blood samples. In human studies, a number of simple indexes, derived from fasting glucose and insulin levels, have been obtained and validated against the glucose-clamp. Since, these indexes have not been validated in rats and their accuracy in predicting altered insulin sensitivity remains to be established. In the present study, we have evaluated whether indirect estimates based on fasting glucose and insulin levels are valid predictors of insulin sensitivity in non-pregnant and 20-day pregnant Wistar and Sprague Dawley rats. We have analyzed HOMA-IR, QUICKI and FGIR by comparing them with the insulin sensitivity (SIClamp) values obtained during the hyperinsulinemic-isoglycemic clamp. We have performed a calibration analysis to evaluate the ability of these indexes to accurately predict insulin sensitivity as determined by the reference glucose-clamp. Finally, to assess the reliability of these indexes for the identification of animals with impaired insulin sensitivity, performance of the indexes was analyzed by receiver operating characteristic (ROC) curves in Wistar and Sprague Dawley rats. We found that HOMA-IR, QUICKI and FGIR correlated significantly with SIClamp, exhibited good sensitivity and specificity, accurately predicted SIClamp, and yielded lower insulin sensitivity in pregnant than in non-pregnant rats. Together our data demonstrate that these indexes provide an easy and accurate measure of insulin sensitivity during pregnancy in the rat.




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