Norbert Stefan1,2,3, Harald Staiger4,5,6, Robert Wagner4,5,6, Jürgen Machann5,6,7, Fritz Schick5,6,7, Hans-Ulrich Häring4,5,6, Andreas Fritsche4,5,6. 1. 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. 2. 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. 3. German Center for Diabetes Research (DZD), Tübingen, Germany. norbert.stefan@med.uni-tuebingen.de. 4. 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. 5. Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany. 6. German Center for Diabetes Research (DZD), Tübingen, Germany. 7. Section of Experimental Radiology, University Hospital Tübingen, Tübingen, Germany.
Abstract
AIMS/HYPOTHESIS: 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/ INTERPRETATION: 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.
AIMS/HYPOTHESIS: 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/ INTERPRETATION: 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.
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