Different Effects of Lifestyle Intervention in High- and Low-Risk Prediabetes
figureposted on 2021-10-06, 19:18 authored by Andreas Fritsche, Robert Wagner, Martin Heni, Kostantinos Kantartzis, Jürgen Machann, Fritz Schick, Rainer Lehmann, Andreas Peter, Corinna Dannecker, Louise Fritsche, Vera Valenta, Renate Schick, Peter Paul Nawroth, Stefan Kopf, Andreas FH Pfeiffer, Stefan Kabisch, Ulrike Dambeck, Michael Stumvoll, Matthias Blüher, Andreas L Birkenfeld, Peter Schwarz, Hans Hauner, Julia Clavel, Jochen Seißler, Andreas Lechner, Karsten Müssig, Katharina Weber, Michael Laxy, Stefan Bornstein, Annette Schürmann, Michael Roden, Martin Hrabe de Angelis, Norbert Stefan, Hans-Ulrich Häring
Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested if prediabetic individuals with low risk benefit from conventional LI and individuals with high risk benefit from an intensification of LI in a multi-center randomized controlled intervention over 12 months with 2 years follow up. 1105 prediabetic individuals based on ADA glucose criteria were stratified into a high- and low-risk phenotype, based on previously described thresholds of insulin secretion, insulin sensitivity and liver fat content. Low-risk individuals were randomly assigned to conventional LI according to the DPP protocol or control (1:1), high-risk individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study. In high-risk individuals, the difference between conventional and intensified LI in post-challenge glucose change was -0.29 mmol/l [CI:-0.54;-0.04], p=0.025. Liver fat (-1.34 percentage points [CI:-2.17;-0.50], p=0.002) and cardiovascular risk (-1.82[CI:-3.13-0.50],p=0.007) underwent larger reductions with intensified than with conventional LI. During a follow up of 3 years, intensified compared to conventional LI had a higher probability to normalize glucose tolerance (p=0.008). In conclusion, it is possible in high-risk individuals with prediabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualized, risk-phenotype-based LI may be beneficial for the prevention of diabetes.