Genotype-Guided Diet and Exercise for Cardiometabolic Health

Overseen By Nehal Vekariya, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: Antidiabetics, Hypertension meds

Disqualifiers: Diabetes, Cardiovascular diseases, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how specific genes influence the heart's hormone levels and affect overall heart and metabolic health. Researchers study the impact of diet and exercise on individuals with naturally low hormone levels, particularly those with specific genetic variations. Participants will follow a special diet, known as the "Study diet," and undergo exercise and glucose challenges to measure their body's responses. The trial seeks healthy adults willing to have their genes tested, adhere to the study protocol, and who have no history of diabetes or heart disease. As an unphased trial, it offers participants the chance to contribute to groundbreaking research on genetic influences on heart health.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking more than two hypertension medications or have a history of diabetes or cardiovascular diseases.

What prior data suggests that this protocol is safe for participants?

Research shows that the treatments in this trial are generally safe for participants. Several studies have examined different eating patterns and their effects on health, suggesting that diets tailored to individual genetic profiles can be beneficial without major safety concerns.

Regarding the exercise challenge, research indicates that regular physical activity improves heart health and lowers disease risk. One study on high-intensity exercise found it safe, with most participants handling it well.

The glucose challenge involves drinking a sugary beverage to assess how the body processes sugar. Studies confirm that this test is safe, though it might cause mild side effects like nausea or dizziness for some individuals.

Overall, these components—diet, exercise, and glucose challenge—are commonly used and have a strong safety record in similar research settings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how personalized diet and exercise plans based on an individual's genotype might improve cardiometabolic health. Unlike standard treatments that usually focus on medications or generalized lifestyle advice, this approach tailors interventions to an individual's genetic makeup. This could potentially lead to more effective and efficient improvements in health markers like glucose metabolism and exercise capacity. By understanding how different genotypes respond to specific diets and exercise regimens, this trial could pave the way for personalized healthcare solutions that are more effective than one-size-fits-all approaches.

What evidence suggests that this trial's treatments could be effective for improving cardiometabolic health?

Research shows that hormones called natriuretic peptides (NPs), produced by the heart, are crucial for maintaining heart and metabolic health. This trial will compare the Low NP Genotype Group and the High NP Genotype Group. Studies suggest that diets tailored to a person's genetic makeup can enhance heart and metabolic health by reducing body weight and fat. Participants in both groups will follow a study diet and participate in an exercise challenge. Regular exercise, like the planned challenge, is linked to improved heart and metabolic health, reducing the risk of heart disease and diabetes. The glucose challenge test, which participants will also undergo, assesses how the body processes sugar, and differences in results can indicate varying risks for metabolic diseases. These combined methods aim to improve health in individuals with naturally lower NP levels, who face a higher risk of heart and metabolic issues. ^{1 2 3 6 7}

Who Is on the Research Team?

Pankaj Arora, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults over 18 without a history of severe heart conditions like congestive heart failure, heart attack, or stroke. Participants should not be on insulin therapy but must be willing to follow the study protocol and consent to genetic material collection.

Inclusion Criteria

I do not take insulin.

You agree to follow the rules of the study.

I agree to provide samples for genetic testing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Dietary Intervention

Participants consume the study diet for 5 days

5 days

No visits required

Exercise Challenge

Participants undergo an exercise challenge test

1 day

1 visit (in-person)

Glucose Challenge

Participants consume 75 gm of oral glucose followed by blood collection every 8 hours

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the challenges

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exercise capacity VO2 max determination
• Exercise Challenge
• Glucose Challenge
• Study diet

Trial Overview The GENESIS study is looking at how diet and exercise affect hormones produced by the heart called Natriuretic Peptides (NP), which are linked to cardiometabolic health. It will involve an exercise challenge, glucose challenge, and VO2 max determination.

How Is the Trial Designed?

Group I: Experimental: Low NP Genotype Group Experimental Treatment 4 Interventions

150 healthy 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.

Group II: Active Comparator: High NP Genotype Group Experimental Treatment 4 Interventions

50 healthy 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.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 105 participants with impaired glucose tolerance or type 2 diabetes, 90% showed improved insulin sensitivity after 12 to 16 weeks of aerobic exercise training, indicating that exercise can significantly enhance metabolic health.

The variability in glycemic control improvements was primarily linked to changes in pancreatic β-cell function, particularly in insulin secretion, rather than insulin sensitivity, suggesting that individual responses to exercise may depend on baseline β-cell function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic β-cell function is a stronger predictor of changes in glycemic control after an aerobic exercise intervention than insulin sensitivity. Solomon, TP., Malin, SK., Karstoft, K., et al.[2022]

An individualized algorithm for administering rapid-acting insulin after morning resistance exercise effectively reduced post-exercise hyperglycemia in individuals with Type 1 diabetes, as shown by a greater decline in blood glucose levels compared to those who did not receive insulin.

The study involved eight participants and demonstrated that this insulin administration did not lead to any episodes of hypoglycemia, indicating a safe approach to managing blood sugar levels post-exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Algorithm that delivers an individualized rapid-acting insulin dose after morning resistance exercise counters post-exercise hyperglycaemia in people with Type 1 diabetes. Turner, D., Luzio, S., Gray, BJ., et al.[2016]

In a study involving 27 participants with type 1 diabetes, an automated insulin delivery (AID) system that used real-time exercise data (exMPC) showed a significant reduction in mean glucose levels during exercise compared to a standard AID system (exAPD), indicating improved glucose management during physical activity.

Both AID systems effectively reduced the time spent in hypoglycemia and maintained glucose levels within the target range, demonstrating that integrating wearable fitness data into insulin dosing can enhance safety and efficacy for individuals with type 1 diabetes during exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating metabolic expenditure information from wearable fitness sensors into an AI-augmented automated insulin delivery system: a randomised clinical trial. Jacobs, PG., Resalat, N., Hilts, W., et al.[2023]

In older adults (70-89 years), those with the ACE D-allele showed a greater improvement in gait speed from a yearlong physical activity program (30%) compared to ACE II homozygotes (19%), suggesting genetic factors influence response to exercise.

Physical activity significantly reduces genetic risks for obesity and hypertriglyceridemia, with active individuals experiencing a 40%-50% reduction in obesity risk and a 30%-40% reduction in hypertriglyceridemia risk, highlighting the protective role of exercise against genetic predispositions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in exercise, fitness, and performance genomics in 2014. Loos, RJ., Hagberg, JM., Pérusse, L., et al.[2018]

Patients with mitochondrial DNA mutations showed significantly lower physical activity levels compared to healthy controls, highlighting the impact of genetic factors on exercise capacity.

A strong association was found between the ACVRIB gene variant (rs2854464) and knee extensor strength, confirmed in two cohorts, suggesting that specific genetic variations can influence muscular strength.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in exercise, fitness, and performance genomics in 2011. Roth, SM., Rankinen, T., Hagberg, JM., et al.[2021]

In a study involving 38 adults with type 2 diabetes, the DPP4-inhibitor sitagliptin improved cardiac diastolic function but did not lead to any changes in cardiorespiratory fitness (CRF) after 3 months of treatment.

Both sitagliptin and glimepiride effectively reduced fasting glucose levels compared to placebo, but targeting physiological contributors to CRF with sitagliptin alone was insufficient to enhance CRF in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sitagliptin improves diastolic cardiac function but not cardiorespiratory fitness in adults with type 2 diabetes. Scalzo, RL., Rafferty, D., Schauer, I., et al.[2022]

In a study of 12 healthy volunteers, higher cardiorespiratory fitness (CRF), measured by peak oxygen uptake (VO2peak), was strongly associated with better insulin sensitivity, as indicated by positive correlations with glucose infusion rates at rest and during exercise.

The findings suggest that maintaining good CRF is crucial for normal insulin action and metabolic health, as higher VO2peak was linked to lower insulin secretion, indicating a more efficient insulin response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiorespiratory fitness predicts insulin action and secretion in healthy individuals. Larsen, FJ., Anderson, M., Ekblom, B., et al.[2018]

In a study involving 251 participants with type 2 diabetes, metformin users showed a significant reduction in HbA1c levels after aerobic training compared to control, while non-users did not show this benefit.

Metformin did not negatively impact changes in fitness, body weight, or waist circumference resulting from exercise, suggesting it does not hinder the positive effects of exercise on glycaemic control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does metformin modify the effect on glycaemic control of aerobic exercise, resistance exercise or both? Boulé, NG., Kenny, GP., Larose, J., et al.[2022]

Individuals with type 1 diabetes (T1D) showed stable blood glucose (BG) levels during cardiopulmonary exercise testing (CPET), indicating that exercise does not significantly alter BG in this population.

Higher preexercise BG levels were associated with increased heart rate and lactate production during exercise, while HbA1c levels were linked to lower peak performance outcomes, suggesting that long-term glucose control impacts exercise capacity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood Glucose Responses during Cardiopulmonary Incremental Exercise Testing in Type 1 Diabetes: A Pooled Analysis. McCarthy, O., Pitt, J., Wellman, B., et al.[2023]

The study identified genetic variants, specifically in the RUNX1 and FKBP7 genes, that influence how individuals with type 2 diabetes respond to an intensive lifestyle intervention aimed at improving cardiorespiratory fitness, based on data from 3899 participants in the Look AHEAD trial.

Individuals carrying certain genetic variants showed less improvement in fitness levels (measured in METs) after one year of intervention, suggesting that genetics may play a role in the effectiveness of lifestyle changes for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic modifiers of cardiorespiratory fitness response to lifestyle intervention. Peter, I., Papandonatos, GD., Belalcazar, LM., et al.[2021]

The IL-6 -174 gene polymorphism affects glucose tolerance in sedentary older adults, with significant changes observed in glucose levels after 6 months of aerobic exercise training, particularly in individuals with the GG genotype.

Fasting glucose levels were higher in individuals with the CC genotype at baseline, suggesting that genetic factors may influence diabetes risk and response to exercise interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of the interleukin-6 -174 G/C gene polymorphism on exercise training-induced changes in glucose tolerance indexes. McKenzie, JA., Weiss, EP., Ghiu, IA., et al.[2013]

In a study of 23 participants with type 2 diabetes, the GLP-1 agonist exenatide improved diastolic cardiac function and reduced arterial stiffness, indicating potential cardiovascular benefits.

However, exenatide did not enhance overall exercise capacity, suggesting that combining it with aerobic exercise training may be necessary to fully realize its benefits for patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide improves diastolic function and attenuates arterial stiffness but does not alter exercise capacity in individuals with type 2 diabetes. Scalzo, RL., Moreau, KL., Ozemek, C., et al.[2022]

In a study of 38 pairs of young monozygotic twins, those with higher cardiorespiratory fitness (VO2max) had significantly lower fasting glucose levels, suggesting a link between fitness and better glucose metabolism.

Despite the differences in fitness levels, there were no significant variations in fasting insulin levels between the more and less active twins, indicating that cardiorespiratory fitness may specifically influence glucose regulation rather than insulin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose metabolism in discordant monozygotic twins for cardiorespiratory fitness. Queiroga, MR., Barbieri, RA., Ferreira, SA., et al.[2019]

Exercise significantly improves blood glucose levels and insulin sensitivity in people with diabetes, making it a crucial non-drug approach to managing the condition.

For patients with type 1 diabetes, careful monitoring and adjustments in medication and nutrition are essential during exercise to prevent hypoglycemia, highlighting the need for personalized exercise plans based on individual health factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and diabetes. Zisser, H., Gong, P., Kelley, CM., et al.[2011]

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