Circulating natriuretic peptide concentrations reflect changes in insulin sensitivity over time in the Diabetes Prevention Program.
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ABSTRACT:
SUBMITTER: Walford GA
PROVIDER: S-EPMC4158711 | biostudies-literature | 2014 May
REPOSITORIES: biostudies-literature
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Circulating natriuretic peptide concentrations reflect changes in insulin sensitivity over time in the Diabetes Prevention Program.
Walford Geoffrey A GA Ma Yong Y Christophi Costas A CA Goldberg Ronald B RB Jarolim Petr P Horton Edward E Mather Kieren J KJ Barrett-Connor Elizabeth E Davis Jaclyn J Florez Jose C JC Wang Thomas J TJ
Diabetologia 20140220 5
<h4>Aims/hypothesis</h4>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).<h4>Methods</h4>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), i ...[more]
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Project description:Natriuretic peptides are cardiac-derived hormones that enhance insulin sensitivity and reduce fat accumulation. Low natriuretic peptide levels are associated with increased risk of type 2 diabetes mellitus (DM2); a condition with variable prevalence across racial/ethnic groups. Few studies have examined whether circulating natriuretic peptide levels and their response to preventive interventions for DM2 differ by race/ethnicity. The Diabetes Prevention Program (DPP) is a clinical trial (July 31, 1996- July 31, 2001) that randomized participants to preventive interventions for DM2. Using stored serum samples, we examined N-terminus pro-B-type natriuretic peptide (NT-proBNP) levels in 3,220 individuals (56% white; 19% African-American; 15% Hispanic; 5% American-Indian; 5% Asian). The influence of race/ethnicity on NT-proBNP concentrations at baseline and after two years of treatment with placebo, lifestyle, or metformin was examined with multivariable-adjusted regression. At baseline, NT-proBNP differed significantly by race (P < .001), with the lowest values in African-American individuals. Hispanic individuals also had lower baseline NT-proBNP levels compared with whites (P< .001), while NT-proBNP levels were similar between white, American-Indian, and Asian individuals. At two years of follow-up, NT-proBNP levels decreased in African-Americans in each of the DPP study arms, whereas they were stable or increased in the other racial/ethnic groups. In the DPP, African-American individuals had lower circulating NT-proBNP levels compared with individuals in other racial/ethnic groups at baseline and after two years of preventive interventions. Further studies should examine the cardio-metabolic implications of lower natriuretic peptide levels in African-Americans. Trial Registration: ClinicalTrials.gov NCT00004992.
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Project description:BackgroundThe natriuretic peptide hormones play an important role in salt and blood pressure regulation. In observational studies, obesity and insulin resistance have been consistently associated with lower concentrations of natriuretic peptides. It has been proposed that insulin influences natriuretic peptide production.ObjectiveWe sought to determine the acute effects of insulin administration on natriuretic peptide concentrations.Methods31 men and women (11 lean, 10 overweight, and 10 obese), ages 30-70 years, without cardiovascular disease or overt diabetes underwent a hyperinsulinemic-euglycemic insulin clamp. Plasma concentrations of N-terminal pro atrial natriuretic peptide (NT-proANP) and N-terminal pro B-type natriuretic peptide (NT-proBNP) were measured at baseline and steady-state (the final 30 minutes of the clamp protocol).ResultsFrom baseline to steady-state, insulin levels increased from a mean level of 9.5 to 176.7 ?U/ml (p<0.001). Over this period, circulating NT-proANP concentrations decreased by 9% (-1933 ng/L, p = 0.01). The changes in NT-proANP did not differ between lean, overweight, and obese individuals. Steady-state NT-proANP levels, adjusted for baseline, were lower in individuals with greater insulin resistance, independent of BMI. In contrast to NT-proANP, NT-proBNP levels did not change significantly during the clamp (p = 0.41).ConclusionInsulin administration was associated with a moderate decrease in circulating NT-proANP, but not NT-proBNP. The lowest NT-proANP concentrations were found in insulin-resistant individuals. Further investigations are warranted to elucidate potential mechanisms underlying the effects of insulin on the cardiac hormonal axis.
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