Dataset Information

Atrial natriuretic peptide and type 2 diabetes development--biomarker and genotype association study.

ABSTRACT:

Background

We have recently shown that low plasma levels of mid-regional atrial natriuretic peptide (MR-ANP) predict development of diabetes and glucose progression over time, independently of known risk factors for diabetes development. However, since MR-ANP levels might be influenced by unknown factors causing diabetes, we cannot rule out that such relationship might be confounded. Previous studies have shown an association of a single nucleotide polymorphism rs5068 on the natriuretic peptide precursor A (NPPA) locus gene with higher levels of circulating ANP. Since gene variants are inherited randomly and not subject to confounding, we aimed to investigate whether the variant rs5068 within the NPPA locus is associated with incident type 2 diabetes.

Methods

We genotyped the variant rs5068 within the NPPA locus in 27,307 individuals without known diabetes from the Malmö Diet Cancer Study. Incident diabetes was retrieved through national and regional registers (median follow-up time of 14 years, 2,823 incident diabetes cases).

Results

In Cox regression analysis adjusted for age, sex and BMI, we found that the carriers of at least one copy of the G allele of rs5068 had lower likelihood of incident diabetes within 14 years (HR?=?0.88, 95% CI 0.78-0.99, p?=?0.037).

Conclusion

Our results indicate a role of the ANP system in the etiology of type 2 diabetes and might help provide insight in the metabolic actions of natriuretic peptides and the pathophysiology of type 2 diabetes.

SUBMITTER: Jujic A

PROVIDER: S-EPMC3929630 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Atrial natriuretic peptide and type 2 diabetes development--biomarker and genotype association study.

Jujić Amra A Nilsson Peter M PM Engström Gunnar G Hedblad Bo B Melander Olle O Magnusson Martin M

PloS one 20140219 2

<h4>Background</h4>We have recently shown that low plasma levels of mid-regional atrial natriuretic peptide (MR-ANP) predict development of diabetes and glucose progression over time, independently of known risk factors for diabetes development. However, since MR-ANP levels might be influenced by unknown factors causing diabetes, we cannot rule out that such relationship might be confounded. Previous studies have shown an association of a single nucleotide polymorphism rs5068 on the natriuretic ...[more]

PMID: 24586593

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Project description:Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio?=?0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio?=?0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions. Please see later in the article for the Editors' Summary.

Project description:ObjectivesThis study was conducted to determine whether urinary excretion of C-type natriuretic peptide (CNP) is elevated in acute decompensated heart failure (ADHF) and whether elevated levels predict adverse outcomes.BackgroundUrinary CNP has been detected in patients with heart failure, but its clinical significance and prognostic utility, compared to established kidney injury biomarkers, in ADHF is unknown.MethodsWe measured 24-h urinary excretion and concurrent plasma concentrations of CNP22, CNP53, and NT-CNP53 in 58 ADHF patients and 20 healthy control subjects. Urinary kidney injury molecule (KIM)-1 and neutrophil gelatinase–associated lipocalin (NGAL) and plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) were also measured. Mortality and all-cause rehospitalization/death were assessed over a follow-up of 1.5 ± 0.9 years.ResultsADHF patients had higher urinary excretion of all 3 CNP molecular forms than did controls. Plasma CNP22 and CNP53 were elevated in ADHF but showed limited correlation with urinary excretion, suggesting that mainly renal-derived CNP appears in urine. Plasma NT-proBNP and urinary KIM-1 were also elevated in ADHF (p < 0.0001); urinary NGAL was similar to that in controls. At 6 months, event-free survival values in ADHF patients were 86% for mortality and 59% for all-cause rehospitalization/death. On Cox regression analysis, urinary NT-CNP53 was the only predictor of mortality (hazard ratio: 1.7; 95% confidence interval: 1.1 to 2.4; p = 0.01) and all-cause rehospitalization/death (hazard ratio: 1.8; 95% confidence interval: 1.3 to 2.4; p = 0.0004), even after adjustment. Integrated discrimination analysis suggested that urinary NT-CNP53 combined with plasma NT-proBNP improved the prediction of adverse outcomes.ConclusionsThe findings from this study support the clinical utility of urinary CNP molecular forms. In ADHF, urinary NT-CNP53 correlated with prognosis, better predicted outcomes than did urinary NGAL and KIM-1, and improved the prognostic value of plasma NT-proBNP.

Dataset Information

Atrial natriuretic peptide and type 2 diabetes development--biomarker and genotype association study.

Background

Methods

Results

Conclusion

Publications

Atrial natriuretic peptide and type 2 diabetes development--biomarker and genotype association study.

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