Robert Wagner1,2,3, Louise Fritsche1,2,3, Martin Heni1,2,3, Ellen Fehlert1,2,3, Norbert Stefan1,2,3, Harald Staiger2,3,4,5,6, Hans-Ulrich Häring1,2,3, Andreas Fritsche7,8,9. 1. Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University Hospital of Tübingen, Tübingen, Germany. 2. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany. 3. German Center for Diabetes Research (DZD), Neuherberg, Germany. 4. Interfaculty Centre for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Tübingen, Germany. 5. Department of Pharmacy and Biochemistry, Faculty of Science, Eberhard Karls University Tübingen, Tübingen, Germany. 6. Institute of Experimental Genetics, Helmholtz Centre Munich, German Research Center for Environmental Health, Neuherberg, Germany. 7. Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University Hospital of Tübingen, Tübingen, Germany. andreas.fritsche@med.uni-tuebingen.de. 8. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany. andreas.fritsche@med.uni-tuebingen.de. 9. German Center for Diabetes Research (DZD), Neuherberg, Germany. andreas.fritsche@med.uni-tuebingen.de.
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.
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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Authors: Rohit Babbar; Martin Heni; Andreas Peter; Martin Hrabě de Angelis; Hans-Ulrich Häring; Andreas Fritsche; Hubert Preissl; Bernhard Schölkopf; Róbert Wagner Journal: Front Endocrinol (Lausanne) Date: 2018-03-19 Impact factor: 5.555
Authors: Tina Stopp; Michael Feichtinger; Ingo Rosicky; Gülen Yerlikaya-Schatten; Johannes Ott; Hans Christian Egarter; Christian Schatten; Wolfgang Eppel; Peter Husslein; Martina Mittlböck; Andrea Tura; Christian S Göbl Journal: J Diabetes Res Date: 2020-03-30 Impact factor: 4.011
Authors: Caroline Willmann; Kathrin Brockmann; Robert Wagner; Stephanie Kullmann; Hubert Preissl; Günter Schnauder; Walter Maetzler; Thomas Gasser; Daniela Berg; Gerhard W Eschweiler; Florian Metzger; Andreas J Fallgatter; Hans-Ulrich Häring; Andreas Fritsche; Martin Heni Journal: BMJ Open Diabetes Res Care Date: 2020-11