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Lifestyle changes effective in high-risk pre-diabetes

Intensive lifestyle intervention with plenty of exercise helps people with pre-diabetes improve their blood glucose levels over a period of years and thus delay or even prevent type 2 diabetes, found a large, multi-centre German study.

In particular, individuals with pre-diabetes at highest risk benefited from intensive lifestyle intervention.

This is shown by the evaluation of the Pre-diabetes Lifestyle Intervention Study (PLIS) of the German Center for Diabetes Research (DZD), conducted at eight sites of the centre throughout Germany. The results have been published in the journal Diabetes.

More exercise and healthy eating behaviour help many people with pre-diabetes to normalise their blood glucose levels and avoid developing type 2 diabetes. However, not everyone benefits from a conventional lifestyle intervention (LI). Recent studies show that already in pre-diabetes, there are different subtypes with different risk profiles.

Researchers at DZD therefore investigated, in a multicentre randomised controlled trial, whether people with pre-diabetes and a high risk benefit from an intensification of the intervention and how people with a low risk are affected by a conventional LI compared with no lifestyle changes.

The LI lasted 12 months in each case and the follow-up period was a further two years. A total of 1,105 individuals with pre-diabetes were investigated at various study sites and assigned to a high-risk or low-risk phenotype based on insulin secretion, insulin sensitivity, and liver fat content: 82% of participants completed the study.

People at high risk, who produce too little insulin or suffer from fatty liver with insulin resistance, were randomly assigned to receive conventional LI according to the Diabetes Prevention Program (DPP) or a more intensive intervention with double the amount of required exercise. The results showed that more exercise, i.e. more intensive LI, helps people at high risk improve their blood glucose and cardiometabolic levels and reduce liver fat content to within the normal range.

Conventional LI is less effective

Low-risk participants completed a conventional LI or took part in a control group that received only a one-time brief consultation. “After three years, glucose tolerance was more likely to normalise in participants with conventional LI than in those in the control group,” said Professor Hans-Ulrich Häring of DZD and last author of the study.

There were hardly any differences in insulin sensitivity and secretion, liver fat content and cardiometabolic risk.

Lifestyle intervention based on risk phenotype improves diabetes prevention

“Our study results show that an individualised LI based on the risk phenotype is beneficial for diabetes prevention,” said study leader Professor Andreas Fritsche from the Institute of Diabetes Research and Metabolic Diseases of Helmholtz Munich at the University of Tübingen (IDM) and the Department of Diabetology, Endocrinology and Nephrology (Director: Professor Andreas Birkenfeld) at Tübingen University Hospital. “For successful prevention, we need to identify high-risk patients in the future and focus on providing them with an intensified lifestyle intervention.”

Study details

Different Effects of Lifestyle Intervention in High- and Low-Risk Prediabetes: Results of the Randomized Controlled Prediabetes Lifestyle Intervention Study (PLIS)

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 Pfeiffer, Stefan Kabisch, Ulrike Dambeck, Michael Stumvoll, Matthias Blüher, Andreas 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.

Published in Diabetes on 16 September 2021


Lifestyle intervention (LI) can prevent type 2 diabetes, but response to LI varies depending on risk subphenotypes. We tested whether individuals with pre-diabetes with low risk (LR) benefit from conventional LI and individuals with high risk (HR) benefit from an intensification of LI in a multicenter randomised controlled intervention over 12 months with 2 years’ follow-up.

A total of 1,105 individuals with pre-diabetes based on American Diabetes Association glucose criteria were stratified into an HR or LR phenotype based on previously described thresholds of insulin secretion, insulin sensitivity, and liver fat content. LR individuals were randomly assigned to conventional LI according to the Diabetes Prevention Program (DPP) protocol or control (1:1) and HR individuals to conventional or intensified LI with doubling of required exercise (1:1). A total of 908 (82%) participants completed the study.

In HR individuals, the difference between conventional and intensified LI in post-challenge glucose change was −0.29 mmol/L [95% CI −0.54; −0.04], P = 0.025. Liver fat (−1.34 percentage points [95% CI −2.17; −0.50], P = 0.002) and cardiovascular risk (−1.82 percentage points [95% 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 with conventional LI had a higher probability of normalising glucose tolerance (P = 0.008).

In conclusion, it is possible in HR individuals with pre-diabetes to improve glycemic and cardiometabolic outcomes by intensification of LI. Individualised, risk phenotype–based LI may be beneficial for the prevention of diabetes.

Diabetes Journal article – Different Effects of Lifestyle Intervention in High- and Low-Risk Prediabetes: Results of the Randomized Controlled Prediabetes Lifestyle Intervention Study (PLIS) (Open access)


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Time for a paradigm shift in the deployment of preventive interventions


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