Effects of a long-term lifestyle modification programme on peripheral neuropathy in overweight or obese adults with type 2 diabetes: the Look AHEAD study.

aims/hypothesisThe aim of this study was to evaluate the effects on diabetic peripheral neuropathy (DPN) of a long-term intensive lifestyle intervention (ILI) programme designed to achieve and maintain weight loss.

methodsBeginning in 2001, a total of 5145 overweight or obese people with type 2 diabetes, aged 45-76 years, participating in the multicentre Look AHEAD (Action for Health in Diabetes) study were randomised to ILI (n = 2570) or to a diabetes support and education (DSE) control group (n = 2575) using a web-based management system at the study coordinating centre at Wake Forest School of Medicine (Winston-Salem, NC, USA). Randomisation was stratified by clinical centre and was not revealed to the clinical staff responsible for obtaining data on study outcomes. Because of the nature of the study, patients and the local centre interventionists were not blinded to the study group assignments. In addition, the coordinating centre staff members responsible for data management and statistical analyses were not blinded to the study group assignments. The interventions were terminated in September 2012, 9-11 years after randomisation, but both groups continued to be followed for both primary and secondary outcomes. Neuropathy evaluations included the Michigan Neuropathy Screening Instrument (MNSI) questionnaire completed at baseline in 5145 participants (ILI n = 2570, DSE n = 2575) and repeated annually thereafter and the MNSI physical examination and light touch sensation testing conducted in 3775 participants (ILI n = 1905, DSE n = 1870) 1-2.3 years after discontinuation of the intervention.

resultsAt baseline, the MNSI questionnaire scores were 1.9 ± 0.04 and 1.8 ± 0.04 in the ILI and DSE groups, respectively (difference not statistically significant). After 1 year, when weight loss was maximal in the ILI group (8.6 ± 6.9%) compared with DSE (0.7 ± 4.8%), the respective MNSI scores were 1.7 ± 0.04 and 2.0 ± 0.04 (p ≤ 0.001). Subsequently, the scores increased gradually in both groups, but remained significantly lower in the ILI group for the first 3 years and at the end of follow-up. In both groups, there was a significant association between changes in the MNSI scores and changes in body weight, HbA CONCLUSIONS/

interpretationILI resulted in a significant decrease in questionnaire-based DPN, which was associated with the magnitude of weight loss. In both the ILI and DSE groups, changes in the MNSI score were also related to changes in HbA

trial registrationClinicalTrials.gov NCT00017953.

fundingThis work was funded by the National Institutes of Health through cooperative agreements with the National Institute of Diabetes and Digestive and Kidney Diseases.