Healthy, Natriuretic Peptides, Metabolic Syndrome
Conditions
Keywords
Racial differences
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTStudy diet
Participants will consume the study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB).
OTHERGlucose 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.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Each participant will be enrolled into one of the two groups by race.
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma MRproANP | From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Insulin | At 1 hour after glucose challenge | The difference in serum insulin levels at 1 hour in response to glucose challenge between African-Americans and whites |
| Serum Glucose | At 1 hour after glucose challenge | The difference in serum glucose levels at 1 hour in response to glucose challenge between African-Americans and whites |
| The Difference in Circulating Plasma MRproANP | From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days | 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) |
| Plasma NTproBNP | From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days | 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) |
| Change in Neprilysin (Membrane Metalloendopeptidase) mRNA Expression Levels Between African-Americans and Whites | At baseline | The relative circulating Neprilysin (Membrane Metalloendopeptidase) mRNA quantification (fold change) at baseline between African-Americans and Whites |
Countries
United States
Participant flow
Pre-assignment details
A total of 81 participants agreed to participate in the study following the completion of the informed consent process and were assigned to each Arm/group. We had 7 study dropouts and 2 participants were not able to complete the protocol. A total of 72 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Study diet: Participants will consume the study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB).
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. | 34 |
| 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.
Study diet: Participants will consume the study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB).
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. | 38 |
| Total | 72 |
Baseline characteristics
| Characteristic | Total | African-American | White |
|---|---|---|---|
| Age, Customized | 27 years | 27 years | 26 years |
| Body Mass Index | 26 kg/m^2 | 27 kg/m^2 | 25 kg/m^2 |
| B-type natriuretic peptide (BNP) | 20 pg/mL | 17 pg/mL | 22 pg/mL |
| Creatinine | 0.8 mmol/L | 0.8 mmol/L | 0.8 mmol/L |
| Fasting Glucose | 93.4 mg/dL STANDARD_DEVIATION 9 | 93.7 mg/dL STANDARD_DEVIATION 11.6 | 93.1 mg/dL STANDARD_DEVIATION 5.8 |
| Fasting Insulin | 10.2 mg/dL STANDARD_DEVIATION 13.4 | 14.3 mg/dL STANDARD_DEVIATION 18.4 | 6.6 mg/dL STANDARD_DEVIATION 3.6 |
| Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | 2.5 Ratio STANDARD_DEVIATION 4.2 | 3.6 Ratio STANDARD_DEVIATION 5.8 | 1.5 Ratio STANDARD_DEVIATION 0.9 |
| Mid-regional pro-atrial natriuretic peptide (MRproANP) | 48 pmol/L | 43 pmol/L | 52 pmol/L |
| N-terminal pro-B-type natriuretic peptide (NTproBNP) | 24 pg/mL | 14 pg/mL | 33 pg/mL |
| Percentage of Hematocrit | 40 % | 40 % | 40 % |
| Potassium | 4.1 mmol/L | 4.0 mmol/L | 4.1 mmol/L |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants | 34 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 0 Participants | 38 Participants |
| Sex: Female, Male Female | 40 Participants | 19 Participants | 21 Participants |
| Sex: Female, Male Male | 32 Participants | 15 Participants | 17 Participants |
| Sodium | 139 mmol/L | 139 mmol/L | 139 mmol/L |
| Systolic Blood Pressure | 114 mmHg | 115 mmHg | 112 mmHg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 38 |
| other Total, other adverse events | 0 / 34 | 0 / 38 |
| serious Total, serious adverse events | 0 / 34 | 0 / 38 |
Outcome results
Primary
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)
Time frame: From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American | Plasma MRproANP | 23 Percentage of change |
Secondary
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
Time frame: At baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| African-American | Change in Neprilysin (Membrane Metalloendopeptidase) mRNA Expression Levels Between African-Americans and Whites | 3.4 fold change | Standard Error 0.79 |
| Whites | Change in Neprilysin (Membrane Metalloendopeptidase) mRNA Expression Levels Between African-Americans and Whites | 1.0 fold change | Standard Error 0.15 |
Secondary
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)
Time frame: From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| African-American | Plasma NTproBNP | -1 Percentage | Standard Error 0.2 |
| Whites | Plasma NTproBNP | -3 Percentage | Standard Error 0.3 |
Secondary
Serum Glucose
The difference in serum glucose levels at 1 hour in response to glucose challenge between African-Americans and whites
Time frame: At 1 hour after glucose challenge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| African-American | Serum Glucose | 129.9 mg/dL | Standard Error 7.3 |
| Whites | Serum Glucose | 126.8 mg/dL | Standard Error 6.2 |
Secondary
Serum Insulin
The difference in serum insulin levels at 1 hour in response to glucose challenge between African-Americans and whites
Time frame: At 1 hour after glucose challenge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| African-American | Serum Insulin | 98.5 µU/mL | Standard Deviation 10.1 |
| Whites | Serum Insulin | 69.7 µU/mL | Standard Deviation 6.7 |
Secondary
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)
Time frame: From 1st hour to 10th hour on the main study visit day after consuming study meals for 3 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| African-American | The Difference in Circulating Plasma MRproANP | 23 Percentage change |
| Whites | The Difference in Circulating Plasma MRproANP | 34 Percentage change |