Racial Differences in the Natriuretic Peptide Response to Glucose Challenge

A Study of Racial Differences in Natriuretic Peptides Response to Glucose Challenge

The purpose of the study is to discover any racial dissimilarity in the response of Natriuretic peptide (NP) system to acute metabolic influences such as a high carbohydrate challenge

Study Overview

• Status: Completed
• Conditions: Healthy; Metabolic Syndrome; Natriuretic Peptides
• Intervention / Treatment: Dietary supplement: Study diet; Other: Glucose Challenge

Detailed Description

Previous studies have shown an association between reduced levels of circulating natriuretic peptides (NPs) and obesity in humans. This association is especially pronounced in those with metabolic syndrome traits and elevated plasma insulin. As previously conducted study has shown that an increase in NPs with weight loss in obese individuals is "primary" and not secondary to alteration in cardiac structure or function.

Previous experimental data suggests that Atrial NP (ANP) has a wide range of favorable metabolic effects including that activation of brown fat and improvement in skeletal muscle oxidative capacity and glucose utilization. New evidence suggests that ANP activation directly modulates insulin sensitivity and energy homeostasis, suggesting that ANP suppression could promote more obesity/insulin resistance. Moreover, ANP exerts potent lipolytic effects in vitro and in vivo. The previous study has shown that a high-carbohydrate challenge in healthy volunteers is associated with a reduction in N-terminal-proANP (NTproANP) but not N-terminal-proB-type NP (NTproBNP) levels. Nonetheless our outcomes were predominantly in Caucasians and warrants replication in other racial groups.

There is no data on the ANP response to high-carbohydrate challenge in African Americans, a racial group with disproportionately greater rates of obesity, insulin resistance, and diabetes as compared to Caucasians. So the investigators have proposed to conduct a pilot study in otherwise healthy, normotensive subjects to examine NP system, especially the effects on MRproANP in response of high-carbohydrate challenge.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18-40 years
• Blood pressure less than 140/90
• Estimated creatinine clearance >60cc/min
• Willingness to comply with the study diet

Exclusion Criteria:

• History of hypertension
• History of cardiovascular, renal, or liver disease
• Diabetes or use of glucose-lowering medications
• Use of vasoactive or diuretic medications
• Atrial fibrillation
• Anemia (Hematocrit < 41% in men and <35% in women
• Abnormal serum sodium or potassium
• Urine β-HCG consistent with pregnancy
• Abnormal liver function tests (>3x upper limit of normal)
• Women taking hormonal birth control
• Current smokers
• Regular users of non-steroid anti-inflammatory medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: African-American; Healthy self-identified African-American participants will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will consume the study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB). On 4th day, participants will come to the clinic in fasting state and drink 75 gm of oral glucose solution, followed by blood collection every hour for 8 hours.	Dietary supplement: Study diet; Participants will consume the study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB).; Other: Glucose Challenge; Participants will come in fasting state on the main study visit day and will be given 75 gm oral glucose solution to drink, followed by blood collection every hour for next 8 hours.
Active Comparator: White; Healthy self-identified white participants will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will consume the study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB). On 4th day, participants will come to the clinic in fasting state and drink 75 gm of oral glucose solution, followed by blood collection every hour for 8 hours.	Dietary supplement: Study diet; Participants will consume the study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB).; Other: Glucose Challenge; Participants will come in fasting state on the main study visit day and will be given 75 gm oral glucose solution to drink, followed by blood collection every hour for next 8 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma MRproANP	Change in circulating MRproANP levels in response to glucose challenge in African-Americans (Linear mixed models using MRproANP as the dependent variable and time as the independent variable were used. Values are predicted log MRproANP with 95% CI)	From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Difference in Circulating Plasma MRproANP	Change in circulating MRproANP levels in response to glucose challenge between African-Americans and whites (Linear mixed models using MRproANP as the dependent variable and time as the independent variable were used. Values are predicted log MRproANP with 95% CI)	From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days
Serum Insulin	The difference in serum insulin levels at 1 hour in response to glucose challenge between African-Americans and whites	At 1 hour after glucose challenge
Serum Glucose	The difference in serum glucose levels at 1 hour in response to glucose challenge between African-Americans and whites	At 1 hour after glucose challenge
Plasma NTproBNP	Change in circulating NTproBNP levels in response to glucose challenge in African-Americans and Whites (Linear mixed models using MRproANP as the dependent variable and time as the independent variable were used. Values are predicted log NTproBNP with 95% CI)	From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days
Change in Neprilysin (Membrane Metalloendopeptidase) mRNA Expression Levels Between African-Americans and Whites	The relative circulating Neprilysin (Membrane Metalloendopeptidase) mRNA quantification (fold change) at baseline between African-Americans and Whites	At baseline

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Pankaj Arora, MD, University of Alabama at Birmingham

Publications and helpful links

General Publications

• Arora P, Wu C, Hamid T, Arora G, Agha O, Allen K, Tainsh RET, Hu D, Ryan RA, Domian IJ, Buys ES, Bloch DB, Prabhu SD, Bloch KD, Newton-Cheh C, Wang TJ. Acute Metabolic Influences on the Natriuretic Peptide System in Humans. J Am Coll Cardiol. 2016 Feb 23;67(7):804-812. doi: 10.1016/j.jacc.2015.11.049.
• Arora P, Reingold J, Baggish A, Guanaga DP, Wu C, Ghorbani A, Song Y, Chen-Tournaux A, Khan AM, Tainsh LT, Buys ES, Williams JS, Heublein DM, Burnett JC, Semigran MJ, Bloch KD, Scherrer-Crosbie M, Newton-Cheh C, Kaplan LM, Wang TJ. Weight loss, saline loading, and the natriuretic peptide system. J Am Heart Assoc. 2015 Jan 16;4(1):e001265. doi: 10.1161/JAHA.114.001265.
• Wu C, Arora P, Agha O, Hurst LA, Allen K, Nathan DI, Hu D, Jiramongkolchai P, Smith JG, Melander O, Trenson S, Janssens SP, Domian I, Wang TJ, Bloch KD, Buys ES, Bloch DB, Newton-Cheh C. Novel MicroRNA Regulators of Atrial Natriuretic Peptide Production. Mol Cell Biol. 2016 Jun 29;36(14):1977-87. doi: 10.1128/MCB.01114-15. Print 2016 Jul 15.
• Patel N, Russell GK, Musunuru K, Gutierrez OM, Halade G, Kain V, Lv W, Prabhu SD, Margulies KB, Cappola TP, Arora G, Wang TJ, Arora P. Race, Natriuretic Peptides, and High-Carbohydrate Challenge: A Clinical Trial. Circ Res. 2019 Nov 8;125(11):957-968. doi: 10.1161/CIRCRESAHA.119.315026. Epub 2019 Oct 6.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: February 27, 2017
• First Submitted That Met QC Criteria: March 2, 2017
• First Posted (Actual): March 7, 2017

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 15, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Racial differences
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Insulin Resistance; Hyperinsulinism; Metabolic Syndrome
• Other Study ID Numbers: X16081002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No