Look AHEAD (Action for Health in Diabetes) is a randomized trial determining whether intensive lifestyle intervention (ILI) aimed at long-term weight loss and increased physical fitness reduces cardiovascular morbidity and mortality in overweight and obese individuals with type 2 diabetes compared to control (diabetes support and education, DSE). We investigated the correlates of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker associated with heart failure (HF) risk, in a subsample from 15 of 16 participating centers and tested the hypothesis that ILI decreased NT-proBNP levels. Baseline and 1-year blood samples were assayed for NT-proBNP in a random sample of 1,500 without, and all 628 with, self-reported baseline CVD (cardiovascular disease) (n = 2,128). Linear models were used to assess relationships that log-transformed NT-proBNP had with CVD risk factors at baseline and that 1-year changes in NT-proBNP had with intervention assignment. At baseline, the mean (SD) age, BMI, and hemoglobin A1c (HbA1c) were 59.6 (6.8) years, 36.0 kg/m2 (5.8), and 7.2% (1.1), respectively. Baseline geometric mean NT-proBNP was not different by condition (ILI 53.3 versus DSE 51.5, p = 0.45), was not associated with BMI, and was inversely associated with HbA1c. At 1 year, ILI participants achieved an average weight loss of 8.3% compared to 0.7% in DSE. At 1 year, NT-proBNP levels increased to a greater extent in the intervention arm (ILI +21.3% versus DSE +14.2%, p = 0.046). The increased NT-proBNP associated with ILI was correlated with changes in HbA1c, BMI, and body composition. In conclusion, among overweight and obese persons with diabetes, an ILI that reduced weight was associated with an increased NT-proBNP.

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