Abstract
Aims
Insulin resistance underlies the etiology of both type 2 diabetes and gestational diabetes. In pregnancy, insulin resistance is also associated with an unfavorable metabolic programming of the fetus, potentially contributing to a higher risk of obesity and type 2 diabetes in the offspring. To assess insulin sensitivity, several methods based on glucose and insulin levels during a 75-g oral glucose tolerance test (OGTT) exist. It is unclear how they perform during pregnancy, where physiologically altered metabolism could introduce a bias.
Methods
In a cohort comprising 476 non-diabetic subjects undergoing OGTT and hyperinsulinemic-euglycemic clamp (HEC), we used cross-validation to develop an insulin sensitivity index also based on non-esterified fatty acids (NEFA) that could be more robust during pregnancy (NEFA-index). We tested commonly used OGTT-based indexes and the NEFA-index in a different cohort of 42 women during pregnancy and 1 year after delivery.
Results
The Matsuda and OGIS index failed to detect lower insulin sensitivity during pregnancy as compared to the follow-up OGTT 1 year after delivery (p > 0.09). The new NEFA-index incorporating BMI, plasma insulin and NEFA, but not glucose, clearly indicated lower insulin sensitivity during pregnancy (p < 0.0001). In the non-pregnant cohort, this NEFA-index correlated well with the gold-standard HEC-based insulin sensitivity index, and outperformed other tested indexes for the prediction of HEC-measured insulin resistance.
Conclusions
This insulin/NEFA-based approach is feasible, robust, and could be consistently used to estimate insulin sensitivity also during pregnancy.
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Acknowledgments
We thank all the research volunteers for their participation. We gratefully acknowledge the excellent technical assistance of Anja Dessecker, Ellen Kollmar and Andreas Vosseler, all Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University Hospital, Eberhard Karls University, Tübingen.
Author contributions
R.W and L.F. analyzed data and wrote the manuscript. E.F., N.S., H.S, H-U. H, M.H contributed to discussion and edited the manuscript, A.F. contributed to discussion and wrote the manuscript.
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The authors declare that they have no conflict of interest.
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The studies were approved by the local institutional review board.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.
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Informed consent was obtained from all patients for being included in the study.
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Managed by Antonio Secchi.
Robert Wagner and Louise Fritsche have contributed equally to this work.
An erratum to this article is available at http://dx.doi.org/10.1007/s00592-017-1002-1.
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Wagner, R., Fritsche, L., Heni, M. et al. A novel insulin sensitivity index particularly suitable to measure insulin sensitivity during gestation. Acta Diabetol 53, 1037–1044 (2016). https://doi.org/10.1007/s00592-016-0930-5
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DOI: https://doi.org/10.1007/s00592-016-0930-5