Natriuretic peptide levels and predicting risk of developing new diabetes mellitus and metabolic syndrome

Aims: Define the relationship between N-terminal atrial natriuretic peptide (NT-ANP) levels and incident metabolic syndrome and type 2 diabetes mellitus ('metabolic disease') in healthy adults and develop a risk prediction score.

Materials and methods: Retrospective cohort study of Olmsted County Heart Function Study participants, a random sampling of county residents aged 45 years and older (n = 2042). Clinical data were collected during enrolment between 1997 and 2000 and upon follow-up 4 years later. Outcomes were followed for 8 years. We studied 715 subjects without metabolic disease at enrolment who completed follow-up, assessing incident metabolic disease as the primary outcome. Youden's index was used to identify optimal cut-points and develop the risk score.

Results: Upon multivariate analysis adjusting for age gender, HDL and triglycerides, higher baseline serum NT-ANP levels were associated with a lower risk of metabolic disease (OR: 0.65, CI 0.49-0.85, p = 0.002). Higher baseline serum insulin and aldosterone levels were associated with higher risk of incident metabolic disease (OR: 2.04, CI 1.57-2.65, p < 0.001; OR: 1.43, CI 1.14-1.81, p = 0.002, respectively). Baseline serum NT-ANP < 3337 pg/mL was 96.6% sensitive for future development of metabolic disease. A weighted score including all three biomarkers was 78.6% sensitive and 77.3% specific.

Conclusions: In healthy adults aged 45 years or older, higher baseline NT-ANP levels are associated with a lower four-year risk of developing metabolic disease. Serum NT-ANP levels are a sensitive biomarker of future risk of metabolic disease and have screening utility when combined with insulin and aldosterone levels into a composite score.