Low plasma level of atrial natriuretic peptide predicts development of diabetes: the prospective Malmo Diet and Cancer study

J Clin Endocrinol Metab. 2012 Feb;97(2):638-45. doi: 10.1210/jc.2011-2425. Epub 2011 Nov 23.


Context: The cardiac natriuretic peptides are involved in blood pressure regulation, and large cross-sectional studies have shown lower plasma levels of N-terminal pro-natriuretic peptide levels [N-terminal atrial natriuretic peptide (N-ANP) and N-terminal brain natriuretic peptide (N-BNP)] in patients with insulin resistance, obesity, and diabetes.

Objective: In this study, we prospectively tested whether plasma levels of mid-regional ANP (MR-ANP) and N-BNP predict new-onset diabetes and long-term glucose progression.

Design, setting, and patients: MR-ANP and N-BNP were measured in 1828 nondiabetic individuals of the Malmö Diet and Cancer cohort (mean age 60 yr; 61% women) who subsequently underwent a follow-up exam including an oral glucose tolerance test after a median follow-up time of 16 yr. Logistic regression was used to adjust for covariates.

Results: During follow-up, 301 subjects developed new-onset diabetes. After full multivariate adjustment, MR-ANP was significantly inversely associated with incident diabetes (OR = 0.85; 95% CI = 0.73-0.99; P = 0.034) but not N-BNP (OR = 0.92; 95% CI = 0.80-1.06; P = 0.262). In fully adjusted linear regression models, the progression of fasting glucose during follow-up was significantly inversely related to baseline levels of MR-ANP (P = 0.004) but not N-BNP (P = 0.129). Quartile analyses revealed that the overall association was mainly accounted for by excess risk of incident diabetes in subjects belonging to the lowest quartile of MR-ANP. After full adjustment, the odds ratio for incident diabetes in the bottom compared with the top quartile of MR-ANP was 1.65 (OR = 1.08-2.51, P = 0.019) and 1.43 (OR = 1.04-1.96, P = 0.027) compared with all other subjects.

Conclusion: Low plasma levels of MR-ANP predict development of future diabetes and glucose progression over time, suggesting a causal role of ANP deficiency in diabetes development.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atrial Natriuretic Factor / analysis
  • Atrial Natriuretic Factor / blood*
  • Cohort Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus / blood*
  • Diabetes Mellitus / diagnosis*
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / etiology
  • Diagnostic Techniques, Endocrine
  • Diet
  • Down-Regulation
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Neoplasms / blood
  • Neoplasms / epidemiology
  • Prognosis


  • Atrial Natriuretic Factor