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

Abstract

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.

Fig. 1

Modelling change in log of NT-proBNP from baseline to follow-up by change in log of ISI and change in BMI or change in WC. (a) The relationship (linear regression slopes and 95% CI) between change in log NT-proBNP and change in BMI (black circles) or log ISI (black triangles). (b) The relationship (linear regression slopes and 95% CI) between change in log NT-proBNP and change in WC (black circles) or log ISI (black triangles). The point estimates are similar across all treatment groups, suggesting that the relationship between change in log NT-proBNP and change in BMI, WC or log ISI are consistent regardless of the intervention. The 95% CIs for the relationship between change in NT-proBNP and BMI or WC crosses 0 in all treatment groups, demonstrating no statistically significant relationship. Predictors (change in log ISI, BMI and WC) are scaled by their SDs in all regression models. All models were adjusted for age; sex; ethnicity; and baseline log NT-proBNP, log ISI and BMI or WC

Fig. 1

Modelling change in log of NT-proBNP from baseline to follow-up by change in log of ISI and change in BMI or change in WC. (a) The relationship (linear regression slopes and 95% CI) between change in log NT-proBNP and change in BMI (black circles) or log ISI (black triangles). (b) The relationship (linear regression slopes and 95% CI) between change in log NT-proBNP and change in WC (black circles) or log ISI (black triangles). The point estimates are similar across all treatment groups, suggesting that the relationship between change in log NT-proBNP and change in BMI, WC or log ISI are consistent regardless of the intervention. The 95% CIs for the relationship between change in NT-proBNP and BMI or WC crosses 0 in all treatment groups, demonstrating no statistically significant relationship. Predictors (change in log ISI, BMI and WC) are scaled by their SDs in all regression models. All models were adjusted for age; sex; ethnicity; and baseline log NT-proBNP, log ISI and BMI or WC