Advertisement

Diabetologia

, Volume 57, Issue 5, pp 935–939 | Cite as

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

  • Geoffrey A. Walford
  • Yong Ma
  • Costas A. Christophi
  • Ronald B. Goldberg
  • Petr Jarolim
  • Edward Horton
  • Kieren J. Mather
  • Elizabeth Barrett-Connor
  • Jaclyn Davis
  • Jose C. FlorezEmail author
  • Thomas J. WangEmail author
  • for the Diabetes Prevention Program Research Group
Short Communication

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.

Keywords

Diabetes prevention Insulin sensitivity Natriuretic peptides NT-proBNP Obesity 

Abbreviations

BNP

B-type natriuretic peptide

DPP

Diabetes Prevention Program

ISI

Insulin sensitivity index

IPW

Inverse probability weighting

NT-proBNP

N-terminal pro-B-type natriuretic peptide

WC

Waist circumference

Notes

Acknowledgements

The investigators gratefully acknowledge the commitment and dedication of the participants of the DPP. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) provided funding to the clinical centres and the coordinating centre for the design and conduct of the study, and for the collection, management, analysis and interpretation of the data. The Southwestern American Indian centres were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources supported data collection at many of the clinical centres. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Centers for Disease Control and Prevention, the Office of Research on Women’s Health, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported, in part, by the Intramural Research Program of the NIDDK. LifeScan, Health O Meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck, Nike Sports Marketing, Slim Fast Foods and Quaker Oats donated materials, equipment or medicines for concomitant conditions. McKesson BioServices, Matthews Media Group and the Henry M. Jackson Foundation provided support services under subcontract with the coordinating centre.

The opinions expressed are those of the investigators and do not necessarily reflect the views of the funding agencies. A complete list of centres, investigators and staff can be found in the ESM.

Funding

GAW received support from NIH training grant DK007028, from the Scholars in Clinical Science Program of Harvard Catalyst—The Harvard Clinical and Translational Science Center (award no. UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic healthcare centres), and the American Diabetes Association Merck Clinical and Translational Post-doctoral Fellowship. R01-HL-08675 (TJW) supported the natriuretic peptide measurements. JCF is supported by R01 DK072041 from NIDDK.

Duality of interest

TJW has received assay or research support from Diasorin, Singulex, Siemens, Brahms and Critical Diagnostics, as well as consulting fees or honoraria from Diasorin, Singulex and Roche Diagnostics. PJ has received Grant/Research Support from Abbott, AstraZeneca, Beckman Coulter, Daiichi Sankyo, GlaxoSmithKline, Merck, Roche Diagnostics, Takeda, and Waters Technologies and Salary/Consulting fees from T2 Biosystems and Quanterix. All other authors declare that they have no duality of interest in relation to the study.

Contribution statement

All authors made substantial contributions to the manuscript and gave final approval of the version to be published. GAW, YM, JCF and TJW conceived the design, interpreted the data, drafted and revised the manuscript. CAC, RBG, PJ, EH, KJM, EB-C and JD interpreted the data and reviewed and revised the article for critical content. GAW is responsible for the integrity of the work as a whole.

Supplementary material

125_2014_3183_MOESM1_ESM.pdf (112 kb)
ESM Research Group List (PDF 112 kb)

References

  1. 1.
    Wang TJ, Larson MG, Levy D et al (2004) Impact of obesity on plasma natriuretic peptide levels. Circulation 109:594–600PubMedCrossRefGoogle Scholar
  2. 2.
    Das SR, Drazner MH, Dries DL et al (2005) Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study. Circulation 112:2163–2168PubMedCrossRefGoogle Scholar
  3. 3.
    Wang TJ, Larson MG, Keyes MJ, Levy D, Benjamin EJ, Vasan RS (2007) Association of plasma natriuretic peptide levels with metabolic risk factors in ambulatory individuals. Circulation 115:1345–1353PubMedCrossRefGoogle Scholar
  4. 4.
    Magnusson M, Jujic A, Hedblad B et al (2012) Low plasma level of atrial natriuretic peptide predicts development of diabetes: the prospective Malmö Diet and Cancer Study. J Clin Endocrinol Metab 97:638–645PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Lazo M, Young JH, Brancati FL et al (2013) NH2-terminal pro-brain natriuretic peptide and risk of diabetes. Diabetes 62:3189–3193PubMedCrossRefGoogle Scholar
  6. 6.
    The Diabetes Prevention Program Research Group (1999) The Diabetes Prevention Program. Design and methods for a clinical trial in the prevention of type 2 diabetes. Diabetes Care 22:623–634PubMedCentralCrossRefGoogle Scholar
  7. 7.
    The Diabetes Prevention Program Research Group (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403CrossRefGoogle Scholar
  8. 8.
    The Diabetes Prevention Program Research Group (2000) The Diabetes Prevention Program: baseline characteristics of the randomized cohort. Diabetes Care 23:1619–1629PubMedCentralCrossRefGoogle Scholar
  9. 9.
    Fuller WA (1975) Regression analysis for sample survey. Sankhyā 37:117–132Google Scholar
  10. 10.
    The Diabetes Prevention Program Research Group (2005) Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program. Diabetes 54:1150–1156PubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Geoffrey A. Walford
    • 1
    • 2
    • 3
    • 4
  • Yong Ma
    • 4
  • Costas A. Christophi
    • 4
  • Ronald B. Goldberg
    • 4
    • 5
  • Petr Jarolim
    • 6
  • Edward Horton
    • 2
    • 4
    • 7
  • Kieren J. Mather
    • 4
    • 8
  • Elizabeth Barrett-Connor
    • 4
    • 9
    • 10
  • Jaclyn Davis
    • 3
    • 4
  • Jose C. Florez
    • 1
    • 2
    • 3
    • 4
    Email author
  • Thomas J. Wang
    • 11
    Email author
  • for the Diabetes Prevention Program Research Group
  1. 1.Diabetes Research Center (Diabetes Unit)Massachusetts General HospitalBostonUSA
  2. 2.Department of MedicineHarvard Medical SchoolBostonUSA
  3. 3.Center for Human Genetic ResearchMassachusetts General HospitalBostonUSA
  4. 4.Diabetes Prevention Program Data Coordinating Center, The Biostatistics CenterGeorge Washington UniversityRockvilleUSA
  5. 5.Division of Endocrinology, Diabetes, and MetabolismUniversity of Miami Miller School of MedicineMiamiUSA
  6. 6.Division of Clinical Laboratories, Department of PathologyBrigham and Women’s HospitalBostonUSA
  7. 7.Joslin Diabetes CenterBostonUSA
  8. 8.Division of EndocrinologyIndiana University School of MedicineIndianapolisUSA
  9. 9.Department of Family and Preventive MedicineUniversity of California, San Diego School of MedicineLa JollaUSA
  10. 10.Department of MedicineUniversity of California, San Diego School of MedicineLa JollaUSA
  11. 11.Division of CardiologyVanderbilt University Medical CenterNashvilleUSA

Personalised recommendations