title: A high-risk phenotype associates with reduced improvement in glycaemia during a lifestyle intervention in prediabetes.
abstract: OBJECTIVE
  Lack of reversal of prediabetes (impaired glucose tolerance and/or impaired fasting glucose) to normal glucose regulation (NGR) during a lifestyle intervention is strongly associated with a higher incidence of diabetes later in life. In the Tübingen Lifestyle Intervention Program (TULIP) we hypothesised that an at-risk phenotype may exist at baseline that associates with this nonresponse to the intervention.
  
  
  METHODS
  A total of 120 participants of TULIP with prediabetes at baseline were studied. Participants underwent 9 months of lifestyle intervention and had measurements of insulin secretion and insulin sensitivity during a 75 g OGTT, and measurements of liver fat content by proton magnetic resonance spectroscopy.
  
  
  RESULTS
  During the lifestyle intervention, 55% of the participants did not revert to NGR. Even among participants with the largest body fat loss (upper quartile: -6.9 ± 3.3%, mean ± SD), 40% did not revert to NGR. In this regard, we identified at baseline a high-risk phenotype (n = 72) consisting of low disposition index or low insulin sensitivity + nonalcoholic fatty liver disease (NAFLD) and a low-risk phenotype (n = 48, all other traits). While the adjusted decrease in body fat was almost identical between these phenotypes (-5.7 ± 15.3% vs -7.7 ± 15.2%, p = 0.49), the high-risk phenotype had a smaller decrease in adjusted 2 h blood glucose levels (-3.7 ± 20.3% vs -18.5 ± 20.0%, p = 0.0009). In addition, only 31% of the participants with the high-risk phenotype, but 67% with the low-risk phenotype, reverted to NGR (p < 0.0001). The odds ratio for reaching the status NGR was 4.54 (95% CI 2.08, 9.94) for participants having the low-risk phenotype.
  
  
  CONCLUSIONS
  Stratification of individuals with prediabetes at baseline into a high-risk and a low-risk phenotype, based on corrected insulin secretion and insulin-resistant NAFLD, may help to determine the effectiveness of a lifestyle intervention to revert individuals to NGR.
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University Hospital Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany. norbert.stefan@med.uni-tuebingen.de.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany. norbert.stefan@med.uni-tuebingen.de.|German Center for Diabetes Research (DZD), Tübingen, Germany. norbert.stefan@med.uni-tuebingen.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Stefan
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University Hospital Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), Tübingen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Staiger
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University Hospital Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), Tübingen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Wagner
authors.affiliation: Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), Tübingen, Germany.|Section of Experimental Radiology, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Machann
authors.affiliation: Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), Tübingen, Germany.|Section of Experimental Radiology, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Schick
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University Hospital Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), Tübingen, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University Hospital Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.|Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD), Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition; D003430:Cross-Sectional Studies; D005223:Fats / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008019:Life Style; D008099:Liver / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism; D010641:Phenotype; D011236:Prediabetic State / Q000097:blood / Q000628:therapy*; D012306:Risk
chemical_list: D001786:Blood Glucose; D005223:Fats; D007328:Insulin
keywords: Impaired glucose tolerance; Insulin secretion; Insulin sensitivity; Lifestyle intervention; Nonalcoholic fatty liver disease; Normal glucose regulation; Prediabetes