Circulating natriuretic peptide concentrations reflect changes in insulin sensitivity over time in the Diabetes Prevention Program

Aims/hypothesis: We aimed to study the relationship between measures of adiposity, insulin sensitivity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the Diabetes Prevention Program (DPP). Methods: The DPP is a completed clinical trial. Using stored samples from this resource, we measured BMI, waist circumference (WC), an insulin sensitivity index (ISI; [1/HOMA-IR]) and NT-proBNP at baseline and at 2 years of follow-up in participants randomised to placebo (n=692), intensive lifestyle intervention (n=832) or metformin (n=887). Results: At baseline, log NT-proBNP did not differ between treatment arms and was correlated with baseline log ISI (p<0.0001) and WC (p=0.0003) but not with BMI (p=0.39). After 2 years of treatment, BMI decreased in the lifestyle and metformin groups (both p<0.0001); WC decreased in all three groups (p<0.05 for all); and log ISI increased in the lifestyle and metformin groups (both p<0.001). The change in log NT-proBNP did not differ in the lifestyle or metformin group vs the placebo group (p>0.05 for both). In regression models, the change in log NT-proBNP was positively associated with the change in log ISI (p<0.005) in all three study groups after adjusting for changes in BMI and WC, but was not associated with the change in BMI or WC after adjusting for changes in log ISI. Conclusion/interpretation: Circulating NT-proBNP was associated with a measure of insulin sensitivity before and during preventive interventions for type 2 diabetes in the DPP. This relationship persisted after adjustment for measures of adiposity and was consistent regardless of whether a participant was treated with placebo, intensive lifestyle intervention or metformin.