Importance of weight loss maintenance and risk prediction in the prevention of type 2 diabetes: analysis of European Diabetes Prevention Study RCT

Abstract

Background: Prevalence of type 2 diabetes (T2D) is increasing worldwide. T2D prevention by lifestyle intervention is effective. Pragmatic scalable interventions are needed, with evidence to efficiently target and monitor such interventions. We report pooled analyses of data from three European trial cohorts: to analyse T2D incidence, sustained weight loss and utility of risk predictors.

Methods: We analysed data on 749 adults with impaired glucose tolerance (278 men and 471 women, mean age 56 years, mean BMI 31 kgm(-2)) recruited between 1993 and 2003, and randomised to intensive lifestyle intervention (I) or lifestyle advice control (C). The intervention aimed to increase physical activity, modify diet, and promote weight loss≥5%. Using Cox-regression survival analysis, we assessed T2D incidence and the impact on T2D incidence of sustained weight loss, and of baseline cut-point values of FINDRISC score, fasting plasma glucose (FPG), and HbA1c.

Results: Mean follow-up duration was 3.1 years. T2D was diagnosed in 139 participants (I = 45/379, C = 94/370). Cumulative T2D incidence was 57% lower in the intervention compared with the control group (HR 0.42 (95% CI 0.29 to 0.60) P<0.001). Participants with ≥5% weight loss at one year had 65% lower T2D incidence (HR 0.35 (95% CI 0.22 to 0.56) P<0.001); maintaining ≥5% weight loss for two and three years further reduced T2D incidence. Recommended cut-points to identify those at high risk for T2D would have identified different proportions of European Diabetes Prevention Study (EDIPS) participants with similar hazard-ratios for intervention effect.

Conclusions: Pooled analysis of EDIPS trial data reinforces evidence for T2D prevention by lifestyle intervention. Analysis showed the preventive effect of ≥5% weight loss, especially if maintained long term, which has utility for intervention monitoring. Analysis of proposed cut-points demonstrates difficulties in balancing risk and benefit, to efficiently target interventions and suggests evidence is needed to define clinical policy.

Trial registrations: THE FINNISH DIABETES PREVENTION STUDY, HELSINKI, FINLAND: ClinicalTrials.gov; NCT00518167 The SLIM diabetes prevention study, Maastricht, The Netherlands: Clinical Trials.gov; NCT00381186 The EDIPS-Newcastle diabetes prevention study, Newcastle upon Tyne, UK: International Standard Randomised Controlled Trial Number; ISRCTN15670600.

Conflict of interest statement

Competing Interests: The authors have the following interests. M. Walker has been paid for consultancy work by Sanofi. JL has been paid for lectures by MSD and Ely Lilly Finland and paid for travel and meeting expenses by Novo Nordisk. Following completion of: 1 the EDIPS-Newcastle study, LP, M. White, JCM, and M. Walker (with full agreement of the Wellcome Trust); 2 the DPS JL; and 3 the SLIM study EB A-dB; have supplied expertise, data and study samples to Tethys Bioscience, 5858 Horton St, Suite 280 Emeryville, CA 94608. Newcastle University, THL Finland, and Maastricht University received remuneration from Tethys bioscience as well as additional sample analysis data. These resources did not contribute to completion of the submitted work. There are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1. CONSORT Flow chart - recruitment by trial cohort and progress of participants.

The flow chart refers to participants in the EDIPS study with impaired glucose tolerance at baseline.

Figure 2. Forest plot comparison of the three studies contributing to the EDIPS data-set.

Figure 3. Progression to type 2 diabetes by trial arm.

Figure 4. Progression to type 2 diabetes by weight loss achieved and maintained.