Purpose

Natriuretic Peptides (NP) are hormones produced by the heart, and they have a wide range of favorable metabolic benefits. Lower levels of these hormones are associated with an increased likelihood of the development of diabetes and poor cardiometabolic health. Obese and Black individuals have ~30% lower levels of NP and are at a greater risk of developing cardiovascular (CV) events as compared to lean and White counterparts. Some people have common genetic variations that cause them to have ~20% lower NP levels. Similar to other low NP populations, these individuals with low NP genotype (i.e., carrying a common genetic variation called rs5068) are at a greater risk of developing cardiometabolic diseases. By understanding the NP response following the exercise challenge and the glucose challenge in individuals with genetically lower NP levels will help us understand how to improve cardiometabolic health in them.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • Adults: Age more than or equal to 18; an equal number of Males and Females - Consent to the collection of genetic material - Willing to adhere to the study protocol

Exclusion Criteria

  • Age <18, at screening. - BMI >45 kg/m2. - Blood pressure more than 140/90 mmHg. - Participants who are taking more than 2 hypertension medications. - History of diabetes or fasting plasma glucose >126 mg/dl or HbA1C>=6.5% or prior treatment with antidiabetic medication. - Have any past or present history of cardiovascular diseases (stroke, seizure, myocardial infarction, heart failure, transient ischemic attack, angina, or cardiac arrhythmia) - Women who are pregnant or breastfeeding or who can become pregnant and not practicing an acceptable method of birth control during the study (including abstinence); - Estimated GFR < 60 ml/min/1.73 m2; albumin creatinine ratio ≥30 mg/g - Hepatic Transaminase (AST and ALT) levels >3x the upper limit of normal - Anemia (men, Hct < 38%; women, Hct <36%) - Inability to exercise on a treadmill

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Each participant will be enrolled into one of the two groups based on their genotype.
Primary Purpose
Basic Science
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Experimental: Low NP Genotype Group
150 Healthy self-identified African-American and Caucasian adult participants with low NP genotype will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will consume the study diet for 5 days. On 5th day, the participants will come in for an exercise challenge test. On 6th day, participants will come in a fasting state and drink 75 gm of oral glucose, followed by blood collection every 8 hours.
  • Dietary Supplement: Study diet
    Participants will consume the study diet for 5 days provided by the clinical research unit's metabolic kitchen (at UAB)
  • Other: Exercise capacity VO2 max determination
    Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol and will also undergo a DEXA scan to determine the body mass.
  • Other: Exercise Challenge
    Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill and will also undergo a resting energy expenditure test.
  • Other: Glucose Challenge
    Participants will come in fasting state on day 6th and will be given 75 gm oral glucose solution to drink, followed by blood collection every hour for next 8 hours.
Experimental
Active Comparator: High NP Genotype Group
50 Healthy self-identified African-American and Caucasian adult participants with high NP genotype will be enrolled and each will undergo a physical exam and screening tests to determine participants' eligibility. Participants will consume the study diet for 5 days. On 5th day, the participants will come in for an exercise challenge test. On 6th day, participants will come in a fasting state and drink 75 gm of oral glucose, followed by blood collection every 8 hours.
  • Dietary Supplement: Study diet
    Participants will consume the study diet for 5 days provided by the clinical research unit's metabolic kitchen (at UAB)
  • Other: Exercise capacity VO2 max determination
    Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol and will also undergo a DEXA scan to determine the body mass.
  • Other: Exercise Challenge
    Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill and will also undergo a resting energy expenditure test.
  • Other: Glucose Challenge
    Participants will come in fasting state on day 6th and will be given 75 gm oral glucose solution to drink, followed by blood collection every hour for next 8 hours.

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35294
Contact:
Vibhu Parcha, MD
205-934-7936
vparcha@uabmc.edu

More Details

Status
Recruiting
Sponsor
University of Alabama at Birmingham

Study Contact

Vibhu Parcha, MD
205-934-7936
vparcha@uabmc.edu

Detailed Description

Obesity is associated with a greater prevalence of cardiometabolic diseases and is associated with an increased risk of cardiovascular (CV) events (such as heart failure [HF], stroke, myocardial infarction [MI], or heart attack), and death. The heart plays an endocrine role by secreting hormones called Natriuretic Peptides (NP). NP directly regulates blood pressure (BP) by causing dilation of blood vessels and removing sodium and water from the body. Investigators have demonstrated that low levels of NP's can initiate the development of CV diseases. The investigators have also shown that obese individuals have 30-40% lower circulating Atrial NP (ANP) levels compared with lean individuals. Similarly, black individuals have relatively 20-30% lower circulating ANP levels as compared with their white counterparts. Previous experimental data suggest that ANP has a wide range of favorable metabolic effects and regulates energy homeostasis, fatty acid oxidation, lipid metabolism, glucose intolerance, insulin sensitivity, and obesity. Former studies by the investigators have shown that the ANP deficient state in obese and black individuals contributes to lower energy expenditure, poor metabolic profile and promotes the onset of diabetes. Certain genetic factors contribute to the higher predisposition to cardiometabolic disease in individuals with relative ANP deficiency. PI and others have identified a common genetic variant rs5068 is associated with higher plasma ANP levels. The lack of the rs5068 variant has a comparable effect on ANP levels as seen in obese and black individuals and has a causal role in cardiometabolic health regulation. The rs5068 variant is only present in 10-12% of the population, thereby leaving nearly 90% of adults vulnerable to the potential adverse cardiometabolic impact of having a relative ANP deficiency. This indicates that a low ANP genotype is associated with a poor metabolic health profile. Our earlier study, in normotensive healthy lean and obese young adults, demonstrated that a high glucose meal results in reduce ANP levels by 20 30%, which indicates that ANP is a glucose-responsive hormone. The preliminary data from our ongoing clinical trial has shown increased ANP levels with response to the exercise. The impact of genetically determined low ANP levels on the differences in exercise-induced ANP (beneficial) increase and glucose load-induced suppression of ANP (detrimental) is not known in humans. Micro-RNA-425 (miR-425) is a negative regulator of ANP and acts in a genotype-specific manner. In our previous study, the investigators have demonstrated that miR-425 levels decreased by 71% following one week on a high-salt diet compared with a low-salt diet in individuals with low ANP genotype, and no change was seen in high ANP genotype individuals. In vitro experiments in animals showed an increase in cardiac miR-425 levels by 22-30%. The negative regulator of ANP also independently negatively regulates the control of energy expenditure. The responsiveness of mir-425 to glucose challenge and exercise challenge (metabolic perturbations) has not been previously evaluated in humans. Individuals with genetically reduced amounts of ANP will be the focus of our present genotype-guided physiological investigation. Following the glucose and exercise challenges, the investigators will additionally investigate the extent to which miR-425 mediated control of ANP suppression occurs. This study will help in understanding how ANP regulates cardiometabolic health in individuals with genetically lower ANP levels.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.