Low plasma level of atrial natriuretic peptide predicts development of diabetes: The prospective Malmö diet and cancer study

Martin Magnusson, Amra Jujic, Bo Hedblad, Gunnar Engström, Margaretha Persson, Joachim Struck, Nils G. Morgenthaler, Peter Nilsson, Christopher Newton-Cheh, Thomas J. Wang, Olle Melander

Research output: Contribution to journalArticlepeer-review

123 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)638-645
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
StatePublished - Feb 2012
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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