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A novel insulin sensitivity index particularly suitable to measure insulin sensitivity during gestation

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An Erratum to this article was published on 22 May 2017

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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Author notes

    Authors and Affiliations

    1. Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University Hospital of Tübingen, Tübingen, Germany

      Robert Wagner, Louise Fritsche, Martin Heni, Ellen Fehlert, Norbert Stefan, Hans-Ulrich Häring & Andreas Fritsche

    2. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany

      Robert Wagner, Louise Fritsche, Martin Heni, Ellen Fehlert, Norbert Stefan, Harald Staiger, Hans-Ulrich Häring & Andreas Fritsche

    3. German Center for Diabetes Research (DZD), Neuherberg, Germany

      Robert Wagner, Louise Fritsche, Martin Heni, Ellen Fehlert, Norbert Stefan, Harald Staiger, Hans-Ulrich Häring & Andreas Fritsche

    4. Interfaculty Centre for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Tübingen, Germany

      Harald Staiger

    5. Department of Pharmacy and Biochemistry, Faculty of Science, Eberhard Karls University Tübingen, Tübingen, Germany

      Harald Staiger

    6. Institute of Experimental Genetics, Helmholtz Centre Munich, German Research Center for Environmental Health, Neuherberg, Germany

      Harald Staiger

    Authors
    1. Robert Wagner
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    2. Louise Fritsche
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    3. Martin Heni
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    7. Hans-Ulrich Häring
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    Corresponding author

    Correspondence to Andreas Fritsche.

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    The authors declare that they have no conflict of interest.

    Ethical standard

    The studies were approved by the local institutional review board.

    Human and animal rights disclosure

    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.

    Informed consent

    Informed consent was obtained from all patients for being included in the study.

    Additional information

    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

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