PMID- 37769677
OWN - NLM
STAT- MEDLINE
DCOM- 20231030
LR  - 20231126
IS  - 2213-8595 (Electronic)
IS  - 2213-8587 (Linking)
VI  - 11
IP  - 11
DP  - 2023 Nov
TI  - Mechanisms of weight loss-induced remission in people with prediabetes: a 
      post-hoc analysis of the randomised, controlled, multicentre Prediabetes 
      Lifestyle Intervention Study (PLIS).
PG  - 798-810
LID - S2213-8587(23)00235-8 [pii]
LID - 10.1016/S2213-8587(23)00235-8 [doi]
AB  - BACKGROUND: Remission of type 2 diabetes can occur as a result of weight loss and 
      is characterised by liver fat and pancreas fat reduction and recovered insulin 
      secretion. In this analysis, we aimed to investigate the mechanisms of weight 
      loss- induced remission in people with prediabetes. METHODS: In this prespecified 
      post-hoc analysis, weight loss-induced resolution of prediabetes in the 
      randomised, controlled, multicentre Prediabetes Lifestyle Intervention Study 
      (PLIS) was assessed, and the results were validated against participants from the 
      Diabetes Prevention Program (DPP) study. For PLIS, between March 1, 2012, and Aug 
      31, 2016, participants were recruited from eight clinical study centres 
      (including seven university hospitals) in Germany and randomly assigned to 
      receive either a control intervention, a standard lifestyle intervention (ie, 
      DPP-based intervention), or an intensified lifestyle intervention for 12 months. 
      For DPP, participants were recruited from 23 clinical study centres in the USA 
      between July 31, 1996, and May 18, 1999, and randomly assigned to receive either 
      a standard lifestyle intervention, metformin, or placebo. In both PLIS and DPP, 
      only participants who were randomly assigned to receive lifestyle intervention or 
      placebo and who lost at least 5% of their bodyweight were included in this 
      analysis. Responders were defined as people who returned to normal fasting plasma 
      glucose (FPG; <5.6 mmol/L), normal glucose tolerance (<7.8 mmol/L), and HbA(1c) 
      less than 39 mmol/mol after 12 months of lifestyle intervention or placebo or 
      control intervention. Non-responders were defined as people who had FPG, 2 h 
      glucose, or HbA(1c) more than these thresholds. The main outcomes for this 
      analysis were insulin sensitivity, insulin secretion, visceral adipose tissue 
      (VAT), and intrahepatic lipid content (IHL) and were evaluated via linear mixed 
      models. FINDINGS: Of 1160 participants recruited to PLIS, 298 (25.7%) had weight 
      loss of 5% or more of their bodyweight at baseline. 128 (43%) of 298 participants 
      were responders and 170 (57%) were non-responders. Responders were younger than 
      non-responders (mean age 55.6 years [SD 9.9] vs 60.4 years [8.6]; p<0.0001). The 
      DPP validation cohort included 683 participants who lost at least 5% of their 
      bodyweight at baseline. Of these, 132 (19%) were responders and 551 (81%) were 
      non-responders. In PLIS, BMI reduction was similar between responders and 
      non-responders (responders mean at baseline 32.4 kg/m(2) [SD 5.6] to mean at 12 
      months 29.0 kg/m(2) [4.9] vs non-responders 32.1 kg/m(2) [5.9] to 29.2 kg/m(2) 
      [5.4]; p=0.86). However, whole-body insulin sensitivity increased more in 
      responders than in non-responders (mean at baseline 291 mL/[min x m(2)], SD 60 to 
      mean at 12 months 378 mL/[min x m(2)], 56 vs 278 mL/[min x m(2)], 62, to 323 
      mL/[min x m(2)], 66; p<0.0001), whereas insulin secretion did not differ within 
      groups over time or between groups (responders mean at baseline 175 pmol/mmol [SD 
      64] to mean at 12 months 163.7 pmol/mmol [60.6] vs non-responders 158.0 pmol/mmol 
      [55.6] to 154.1 pmol/mmol [56.2]; p=0.46). IHL decreased in both groups, without 
      a difference between groups (responders mean at baseline 10.1% [SD 8.7] to mean 
      at 12 months 3.5% [3.9] vs non-responders 10.3% [8.1] to 4.2% [4.2]; p=0.34); 
      however, VAT decreased more in responders than in non-responders (mean at 
      baseline 6.2 L [SD 2.9] to mean at 12 months 4.1 L [2.3] vs 5.7 L [2.3] to 4.5 L 
      [2.2]; p=0.0003). Responders had a 73% lower risk of developing type 2 diabetes 
      than non-responders in the 2 years after the intervention ended. INTERPRETATION: 
      By contrast to remission of type 2 diabetes, resolution of prediabetes was 
      characterised by an improvement in insulin sensitivity and reduced VAT. Because 
      return to normal glucose regulation (NGR) prevents development of type 2 
      diabetes, we propose the concept of remission of prediabetes in analogy to type 2 
      diabetes. We suggest that remission of prediabetes should be the primary 
      therapeutic aim in individuals with prediabetes. FUNDING: German Federal Ministry 
      for Education and Research via the German Center for Diabetes Research; the 
      Ministry of Science, Research and the Arts Baden-Wurttemberg; the Helmholtz 
      Association and Helmholtz Munich; the Cluster of Excellence Controlling Microbes 
      to Fight Infections; and the German Research Foundation.
CI  - Copyright (c) 2023 Elsevier Ltd. All rights reserved.
FAU - Sandforth, Arvid
AU  - Sandforth A
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - von Schwartzenberg, Reiner Jumpertz
AU  - von Schwartzenberg RJ
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany; Cluster of Excellence Controlling 
      Microbes to Fight Infections, Eberhard-Karls University of Tubingen, Tubingen, 
      Germany.
FAU - Arreola, Elsa Vazquez
AU  - Arreola EV
AD  - Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes 
      and Digestive and Kidney Diseases, Phoenix, AZ, USA.
FAU - Hanson, Robert L
AU  - Hanson RL
AD  - Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes 
      and Digestive and Kidney Diseases, Phoenix, AZ, USA.
FAU - Sancar, Gencer
AU  - Sancar G
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Katzenstein, Sarah
AU  - Katzenstein S
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Lange, Karl
AU  - Lange K
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Preissl, Hubert
AU  - Preissl H
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Dreher, Simon I
AU  - Dreher SI
AD  - German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Weigert, Cora
AU  - Weigert C
AD  - German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Wagner, Robert
AU  - Wagner R
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of 
      Endocrinology and Diabetology, German Diabetes Center, Leibniz Center for 
      Diabetes Research, Heinrich Heine University Dusseldorf, Dusseldorf, Germany; 
      Medical Faculty and University Hospital, Institute for Clinical Diabetology, 
      German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine 
      University Dusseldorf, Dusseldorf, Germany.
FAU - Kantartzis, Kostantinos
AU  - Kantartzis K
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Machann, Jurgen
AU  - Machann J
AD  - German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany; Department of Radiology, Section on 
      Experimental Radiology, Eberhard-Karls University of Tubingen, Tubingen, Germany.
FAU - Schick, Fritz
AU  - Schick F
AD  - German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany; Department of Radiology, Section on 
      Experimental Radiology, Eberhard-Karls University of Tubingen, Tubingen, Germany.
FAU - Lehmann, Rainer
AU  - Lehmann R
AD  - German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany; Institute for Clinical Chemistry and 
      Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University 
      Hospital of Tubingen, Tubingen, Germany.
FAU - Peter, Andreas
AU  - Peter A
AD  - German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany; Institute for Clinical Chemistry and 
      Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University 
      Hospital of Tubingen, Tubingen, Germany.
FAU - Katsouli, Nikoletta
AU  - Katsouli N
AD  - Central Institute for Translational Cancer Research, Technical University of 
      Munich, Munich, Germany; Institute of Biological and Medical Imaging, Helmholtz 
      Zentrum Munchen, Munich, Germany.
FAU - Ntziachristos, Vasilis
AU  - Ntziachristos V
AD  - Central Institute for Translational Cancer Research, Technical University of 
      Munich, Munich, Germany; Institute of Biological and Medical Imaging, Helmholtz 
      Zentrum Munchen, Munich, Germany.
FAU - Dannecker, Corinna
AU  - Dannecker C
AD  - German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Fritsche, Louise
AU  - Fritsche L
AD  - German Center for Diabetes Research, Neuherberg, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Perakakis, Nikolaos
AU  - Perakakis N
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine III, Technical University Dresden, Dresden, Germany.
FAU - Heni, Martin
AU  - Heni M
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Nawroth, Peter Paul
AU  - Nawroth PP
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine 
      I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany.
FAU - Kopf, Stefan
AU  - Kopf S
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine 
      I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany.
FAU - Pfeiffer, Andreas F H
AU  - Pfeiffer AFH
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of 
      Endocrinology and Metabolism, Charite-Universitatsmedizin Berlin, Berlin, 
      Germany.
FAU - Kabisch, Stefan
AU  - Kabisch S
AD  - German Center for Diabetes Research, Neuherberg, Germany; German Institute of 
      Human Nutrition Potsdam-Rehbrucke, Brandenburg, Germany.
FAU - Stumvoll, Michael
AU  - Stumvoll M
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine, 
      Endocrinology and Nephrology, Universitat Leipzig, Leipzig, Germany.
FAU - Schwarz, Peter E H
AU  - Schwarz PEH
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine III, Technical University Dresden, Dresden, Germany.
FAU - Hauner, Hans
AU  - Hauner H
AD  - German Center for Diabetes Research, Neuherberg, Germany; Institute of 
      Nutritional Medicine, Technical University of Munich, Munich, Germany.
FAU - Lechner, Andreas
AU  - Lechner A
AD  - German Center for Diabetes Research, Neuherberg, Germany; Diabetes Research 
      Group, Medical Department, Ludwig-Maximilians University Munich, Munich, Germany.
FAU - Seissler, Jochen
AU  - Seissler J
AD  - German Center for Diabetes Research, Neuherberg, Germany; Diabetes Research 
      Group, Medical Department, Ludwig-Maximilians University Munich, Munich, Germany.
FAU - Yurchenko, Iryna
AU  - Yurchenko I
AD  - German Center for Diabetes Research, Neuherberg, Germany; Medical Faculty and 
      University Hospital, Institute for Clinical Diabetology, German Diabetes Center, 
      Leibniz Center for Diabetes Research, Heinrich Heine University Dusseldorf, 
      Dusseldorf, Germany.
FAU - Icks, Andrea
AU  - Icks A
AD  - German Center for Diabetes Research, Neuherberg, Germany; Institute for Health 
      Services Research and Health Economics, Centre for Health and Society, German 
      Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University 
      Dusseldorf, Dusseldorf, Germany; Institute for Health Services Research and 
      Health Economics, German Diabetes Center, Leibniz Center for Diabetes Research, 
      Heinrich Heine University Dusseldorf, Dusseldorf, Germany.
FAU - Solimena, Michele
AU  - Solimena M
AD  - German Center for Diabetes Research, Neuherberg, Germany; 
      Paul-Langerhans-Institut Dresden, Helmholtz Center Munich, University Clinic Carl 
      Gustav Carus, Dresden, Germany.
FAU - Haring, Hans-Ulrich
AU  - Haring HU
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Szendroedi, Julia
AU  - Szendroedi J
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine 
      I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany.
FAU - Schurmann, Annette
AU  - Schurmann A
AD  - German Center for Diabetes Research, Neuherberg, Germany; German Institute of 
      Human Nutrition Potsdam-Rehbrucke, Brandenburg, Germany.
FAU - de Angelis, Martin Hrabe
AU  - de Angelis MH
AD  - German Center for Diabetes Research, Neuherberg, Germany; School of Medicine and 
      School of Life Sciences Weihenstephan, Technical University of Munich, Munich, 
      Germany; Institute of Experimental Genetics, Helmholtz Center Munich, Munich, 
      Germany.
FAU - Bluher, Matthias
AU  - Bluher M
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Medicine, 
      Endocrinology and Nephrology, Universitat Leipzig, Leipzig, Germany.
FAU - Roden, Michael
AU  - Roden M
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of 
      Endocrinology and Diabetology, German Diabetes Center, Leibniz Center for 
      Diabetes Research, Heinrich Heine University Dusseldorf, Dusseldorf, Germany; 
      Medical Faculty and University Hospital, Institute for Clinical Diabetology, 
      German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine 
      University Dusseldorf, Dusseldorf, Germany.
FAU - Bornstein, Stefan R
AU  - Bornstein SR
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine III, Technical University Dresden, Dresden, Germany; Department of 
      Diabetes, Life Sciences and Medicine, Cardiovascular Medicine and Sciences, Kings 
      College London, London, UK.
FAU - Stefan, Norbert
AU  - Stefan N
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Fritsche, Andreas
AU  - Fritsche A
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany.
FAU - Birkenfeld, Andreas L
AU  - Birkenfeld AL
AD  - German Center for Diabetes Research, Neuherberg, Germany; Department of Internal 
      Medicine IV, Division of Diabetology, Endocrinology and Nephrology, 
      Eberhard-Karls University of Tubingen, Tubingen, Germany; Institute for Diabetes 
      Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard-Karls 
      University of Tubingen, Tubingen, Germany; Department of Diabetes, Life Sciences 
      and Medicine, Cardiovascular Medicine and Sciences, Kings College London, London, 
      UK. Electronic address: andreas.birkenfeld@med.uni-tuebingen.de.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20230925
PL  - England
TA  - Lancet Diabetes Endocrinol
JT  - The lancet. Diabetes & endocrinology
JID - 101618821
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
CIN - Lancet Diabetes Endocrinol. 2023 Nov;11(11):784-785. PMID: 37769678
EIN - Lancet Diabetes Endocrinol. 2024 Jan;12(1):e1. PMID: 38008110
MH  - Humans
MH  - Middle Aged
MH  - *Diabetes Mellitus, Type 2/prevention & control
MH  - *Prediabetic State
MH  - *Insulin Resistance
MH  - Weight Loss
MH  - Body Weight
MH  - Glucose
MH  - Life Style
COIS- Declaration of interests SKab receives grants from the German Diabetes 
      Association, Wilhelm-Doerenkamp-Foundation, and California Walnut Commission and 
      lecture fees from Sanofi, Boehringer Ingelheim, Berlin-Chemie, Lilly Deutschland, 
      and Juzo Akademie. RW receives lecture fees from Eli Lilly, Novo Nordisk, and 
      Sanofi and participates in a Data Safety Monitoring Board and Advisory Board for 
      Eli Lilly. AL receives grants from Helmholtz Munich and Ludwig Maximilian 
      University Klinikum Munchen. NP receives lecture fees from NovoNordisk and 
      Gesellschaft fur Wissenschaftstransfer Dresden; advisory board fees from Bayer 
      Vital; and holds patent WO 2021/092265A1 for diagnosis and treatment of 
      non-alcoholic fatty liver disease and liver fibrosis. VN is the founder and 
      equity owner of sThesis, iThera Medical, Spear UG, and I3. All other authors 
      declare no competing interests.
EDAT- 2023/09/29 00:42
MHDA- 2023/10/30 06:47
CRDT- 2023/09/28 19:27
PHST- 2023/06/13 00:00 [received]
PHST- 2023/08/02 00:00 [revised]
PHST- 2023/08/04 00:00 [accepted]
PHST- 2023/10/30 06:47 [medline]
PHST- 2023/09/29 00:42 [pubmed]
PHST- 2023/09/28 19:27 [entrez]
AID - S2213-8587(23)00235-8 [pii]
AID - 10.1016/S2213-8587(23)00235-8 [doi]
PST - ppublish
SO  - Lancet Diabetes Endocrinol. 2023 Nov;11(11):798-810. doi: 
      10.1016/S2213-8587(23)00235-8. Epub 2023 Sep 25.