Racial Differences in the Natriuretic Peptide 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

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.

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.

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.

Participants will consume the study diet for 3 days provided by the clinical research unit's metabolic kitchen (at UAB).

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.

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)

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)

The difference in serum insulin levels at 1 hour in response to glucose challenge between African-Americans and whites

The difference in serum glucose levels at 1 hour in response to glucose challenge between African-Americans and whites

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

The relative circulating Neprilysin (Membrane Metalloendopeptidase) mRNA quantification (fold change) at baseline between African-Americans and Whites

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

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