Proteinuria Modifies the Effects of Physical Activity on Total and Cardiovascular Disease Mortality Rates in Patients with Type 2 Diabetes

Aims/hypothesis: Physical activity reduces cardiovascular disease (CVD) and total mortality rates in patients with type 2 diabetes. However, it is not known whether or not the effects of physical activity on mortality rates depend on the presence of proteinuria in type 2 diabetic patients.

Methods: We prospectively followed up 577 patients with type 2 diabetes who were aged 45 to 64 years and were free of CVD at baseline. Participants were stratified according to the presence of proteinuria (<or=300 or >300 mg/l) and the degree of physical activity (0-4 metabolic equivalent tasks [MET] or >4 MET). The Cox proportional hazards model was used to estimate the association of physical activity and proteinuria with risk of mortality.

Results: During the 18-year follow-up, 356 patients died, of whom 217 died from CVD. Physically more active patients had significantly reduced total, CVD and CHD mortality rates if they did not have proteinuria. In contrast, physically active proteinuric patients had significantly increased total and CVD mortality rates (HR 1.83, 95% CI 1.00-3.36, p=0.049) in univariate analyses, with HR 2.43 (95% CI 1.09-5.40, p=0.030) in multivariate analyses.

Conclusions/interpretation: Physical activity reduces total and CVD mortality rates in type 2 diabetic patients without proteinuria. However, in proteinuric patients, no protective effect was observed. Larger studies are needed to confirm the latter finding and to define which exercise intensity leads to possible harmful effects.