title: A novel insulin sensitivity index particularly suitable to measure insulin sensitivity during gestation.
abstract: OBJECTIVE
  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.
authors: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University Hospital of Tübingen, Tübingen, Germany.|Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors: Robert
authors: R
authors: Wagner
authors: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University Hospital of Tübingen, Tübingen, Germany.|Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors: Louise
authors: L
authors: Fritsche
authors: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University Hospital of Tübingen, Tübingen, Germany.|Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors: Martin
authors: M
authors: Heni
authors: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University Hospital of Tübingen, Tübingen, Germany.|Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors: Ellen
authors: E
authors: Fehlert
authors: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University Hospital of Tübingen, Tübingen, Germany.|Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors: Norbert
authors: N
authors: Stefan
authors: Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.|Interfaculty Centre for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Tübingen, Germany.|Department of Pharmacy and Biochemistry, Faculty of Science, Eberhard Karls University Tübingen, Tübingen, Germany.|Institute of Experimental Genetics, Helmholtz Centre Munich, German Research Center for Environmental Health, Neuherberg, Germany.
authors: Harald
authors: H
authors: Staiger
authors: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University Hospital of Tübingen, Tübingen, Germany.|Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen (IDM), Tübingen, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors: Hans-Ulrich
authors: HU
authors: Häring
authors: 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.|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.|German Center for Diabetes Research (DZD), Neuherberg, Germany. andreas.fritsche@med.uni-tuebingen.de.
authors: Andreas
authors: A
authors: Fritsche
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis; D016640:Diabetes, Gestational / Q000097:blood / Q000175:diagnosis; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005858:Germany; D015309:Glucose Clamp Technique / Q000379:methods; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood / Q000175:diagnosis; D015203:Reproducibility of Results
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin
keywords: Free fatty acids; Gestational diabetes; Hyperinsulinemic euglycemic clamp; Insulin sensitivity; Non-esterified fatty acids; Pregnancy