Meal Testing for Healthy Subjects

Recruiting at 1 trial location

Overseen By Susanne M Votruba, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must not be taking: Metabolism-altering drugs

Disqualifiers: Diabetes, Anemia, Pregnancy, Alcohol abuse, others

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

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

79 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how different meal sizes affect blood sugar levels in healthy individuals. Researchers are comparing two meal types: fixed meals, which remain the same size for everyone, and adjusted meals that vary based on body size. Participants will undergo various tests, including consuming a liquid meal and having their blood sampled over several hours. The trial seeks healthy individuals aged 18 or older who are not using medications or supplements that affect energy metabolism. As an unphased trial, participants contribute to foundational research that may enhance dietary guidelines for better health.

Will I have to stop taking my current medications?

Yes, if you are currently using medications, dietary supplements, or alternative therapies that alter energy metabolism, you will not be eligible to participate in this study.

What prior data suggests that these meal tests are safe for healthy subjects?

Research has shown that mixed meal tolerance tests (MMTTs) are generally easy for participants to handle, even those with type 1 diabetes. One study found that MMTTs are the best way to measure how the body releases insulin after eating. MMTTs, whether fixed or adjusted, are safe to use and have been trusted in many settings without causing significant problems.

The adjusted MMTT can help predict the onset of type 2 diabetes by measuring how the body responds to sugar. This test is important and safe for collecting useful health information. Meanwhile, the fixed MMTT reliably provides data on insulin release in research, demonstrating its safety and usefulness.

Overall, both fixed and adjusted MMTTs have a strong history of being safe and effective for testing blood sugar and insulin levels. Participants in past studies reported no major safety issues, making these tests a safe option for those interested in joining clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Meal Testing trial because it explores two different methods for assessing metabolic responses in healthy individuals. The Adjusted Mixed Meal Test offers flexibility by tailoring the meal's composition to individual needs, potentially providing more personalized insights into metabolic health. On the other hand, the Fixed Mixed Meal Test provides a consistent baseline for comparison across all subjects, making it easier to identify variations in metabolic responses. This trial could uncover new ways to evaluate and understand metabolism, which might lead to more targeted nutritional recommendations in the future.

What evidence suggests that this trial's treatments could be effective?

This trial will compare two methods: the Adjusted Mixed Meal Test and the Fixed Mixed Meal Test. Research has shown that both adjusted and fixed mixed meal tests (MMTTs) effectively measure how the body processes food. Studies have found that MMTTs assess insulin sensitivity, which helps researchers understand how the body handles sugar. The adjusted MMTT, used in one arm of this trial, customizes to a person's body size, offering a more personalized view of metabolism. In contrast, the fixed MMTT, used in another arm, applies the same meal size for everyone, making it useful for standard comparisons. Both methods are valuable for identifying how different people manage blood sugar, which is important for conditions like diabetes. ^{2 5 6 7 8}

Who Is on the Research Team?

Susanne M Votruba, Ph.D.

Principal Investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Are You a Good Fit for This Trial?

This trial is for healthy adults over 18 years old. It's designed to see how different calorie amounts in meals affect blood sugar levels. Participants will need to visit the clinic several times and undergo various tests, including drinking a sugary solution and having their metabolic rate measured.

Inclusion Criteria

Provision of signed and dated informed consent form

Agreement to adhere to Lifestyle Considerations throughout study duration

Healthy, as determined by medical history, physical examination, and laboratory tests

Exclusion Criteria

Current pregnancy, pregnancy within the past 6 months or currently lactating

Fasting plasma glucose >= 126 mg/dL

Conditions not specifically mentioned above may serve as criteria for exclusion at the discretion of the investigators

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Testing

Participants undergo baseline tests including height, weight, waist size measurements, an oral glucose tolerance test, and a body scan

1 day

1 visit (in-person)

Treatment

Participants undergo 2 Mixed Meal Tolerance Test (MMTT) visits, one with a fixed meal and one with an adjusted meal, including metabolic rate testing and blood sampling

8 weeks

2-3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Adjusted Mixed Meal Test
• Fixed Mixed Meal Test

Trial Overview Researchers are testing two types of mixed meal tolerance tests (MMTTs): one with a fixed caloric dose for everyone, and another adjusted based on individual body size. The goal is to determine which method provides more accurate results for future studies.

How Is the Trial Designed?

Group I: 2 Active Control 1 Intervention

Adjusted Mixed Meal Test

Group II: 1 Active Control 1 Intervention

Fixed Mixed Meal Test

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 894 individuals undergoing mixed-meal tolerance tests (MMTTs), the reproducibility of glucose responses was found to be moderate for breakfast but poor for lunch, indicating variability in how individuals respond to meals based on timing and glucose regulation status.

For those with type 2 diabetes (T2D), the reproducibility of glucose responses was high, suggesting that MMTTs may be more consistent in this group, while insulin responses showed lower reproducibility, highlighting the complexity of insulin dynamics in different glucose regulation states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility and determinants of the metabolic responses during a mixed-meal tolerance test. Stinson, EJ., Piaggi, P., Mitchell, CM., et al.[2023]

The study demonstrated that mixed meal tolerance tests (MMTTs) are reliable for estimating beta-cell function in individuals with type 2 diabetes, showing significantly lower intra-individual variation compared to inter-individual variation in C-peptide, insulin, and glucose responses.

Different macronutrient compositions in liquid meals (specifically varying protein and carbohydrate levels) did not lead to significant changes in C-peptide and insulin responses, indicating that moderate dietary differences may not impact beta-cell function assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of mixed meal tolerance test composition on measures of beta-cell function in type 2 diabetes. Kössler, T., Bobrov, P., Strassburger, K., et al.[2021]

In a study involving 91 adults with insulin-treated diabetes, it was found that omitting insulin during the mixed meal tolerance test may not be necessary, as the results were highly correlated whether insulin was included or not (r = 0.98).

Fasting serum C-peptide levels were also shown to be a practical alternative for assessing endogenous insulin secretion, with a cut-off of ≥ 0.07 nmol/l providing 100% sensitivity and 97% specificity for significant insulin secretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of insulin administration during the mixed meal tolerance test. Besser, RE., Jones, AG., McDonald, TJ., et al.[2022]

Mixed-meal tolerance tests were conducted on healthy controls, type 1A diabetes patients, and fulminant type 1 diabetic patients to assess their metabolic responses after an overnight fast.

The study provides insights into how different types of diabetes affect the body's ability to process mixed meals, highlighting potential differences in metabolic function among these groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Preserved" glucagon secretion in fulminant type 1 diabetes. Murase-Mishiba, Y., Bessho-Tachibana, M., Imagawa, A.[2020]

A standardized meal test produces a more consistent plasma glucose and insulin response compared to the traditional glucose tolerance test, indicating it may better reflect real-life metabolic status.

The glucose tolerance test is primarily useful for diagnosing glucose intolerance, but the standardized meal test shows that carbohydrate tolerance can decrease throughout the day, highlighting the importance of testing conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the metabolic response to a glucose tolerance test and a standardized test meal and the response to serial test meals in normal healthy subjects. Owens, DR., Wragg, KG., Briggs, PI., et al.[2019]

A fixed combination of 10 mg mitiglinide and 0.2 mg voglibose significantly reduced postprandial hyperglycemia in type 2 diabetes patients after breakfast, lunch, and dinner, indicating its efficacy in managing blood sugar levels throughout the day.

The treatment improved metabolic responses by increasing insulin and C-peptide levels while decreasing free fatty acids and triglycerides, confirming its beneficial effects on glycemic control in T2DM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The glycemic/metabolic responses to meal tolerance tests at breakfast, lunch and dinner, and effects of the mitiglinide/voglibose fixed-dose combination on postprandial profiles in Japanese patients with type 2 diabetes mellitus. Ono, Y., Nakamura, A., Cho, KY., et al.[2019]

In a study of 41 patients with monogenic diabetes, the mixed meal tolerance test (MMTT) effectively assessed beta-cell function, revealing that patients with GCK mutations had significantly better beta-cell responses compared to those with HNF4A and KCNJ11 mutations.

The study identified a baseline C-peptide level of 133.5 pmol/L as a predictive marker for successfully switching patients to oral sulfonylurea treatment, suggesting that MMTT can guide treatment decisions after molecular diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kinetics of C-peptide during mixed meal test and its value for treatment optimization in monogenic diabetes patients. Stankute, I., Verkauskiene, R., Dobrovolskiene, R., et al.[2021]

In a study involving six individuals who underwent weight loss interventions, the liquid-mixed meal was found to be the most tolerable, with a 99% completion rate, compared to solid-mixed and high-fat meals.

The liquid-mixed meal also induced significantly higher levels of incretin hormones and insulin secretion, making it the preferred choice for evaluating glucose metabolism in post-weight loss patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of meal composition on postprandial incretin, glucose and insulin responses after surgical and medical weight loss. Lee, CJ., Brown, TT., Cheskin, LJ., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6487945/

Mixed‐meal tolerance test to assess residual beta‐cell ... We analyzed data obtained from 32 participants with newly diagnosed type 1 diabetes (age 12.4[2.9] years, 12 males, HbA1c 6.8%[1.1], BMI SDS 0.62[1.02], total ...

2. nature.com nature.com/articles/s41366-025-01866-7

The mixed-meal tolerance test as an appetite assay The primary outcomes typically include appetite perceptions (i.e. visual analogues scales [VAS] for hunger, fullness, satisfaction & desire-to- ...

3. diabetesjournals.org diabetesjournals.org/care/article/39/9/1602/37075/Standardized-Mixed-Meal-Tolerance-and-Arginine

Standardized Mixed-Meal Tolerance and Arginine Stimulation ... The MMTT offers a simple-to-administer physiologic test that incorporates the incretin response. When analyzed with the minimal model, the MMTT ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0168822721002989

Kinetics of C-peptide during mixed meal test and its value ... We analyzed MMTT data of these patients retrospectively and compared the kinetics of CP of “successful” and “unsuccessful” treatment change groups.

5. mdpi.com mdpi.com/2077-0383/12/13/4295

Mixed Meal Tolerance Test Versus Continuous Glucose ... In this study, we evaluated the usefulness of a mixed meal tolerance test (MMTT) and continuous glucose monitoring (CGM) for the diagnosis of PBH.

6. nature.com nature.com/articles/s41387-024-00269-3

A mixed meal tolerance test predicts onset of type 2 ... Glucose responses to a mixed meal predicted the development of type 2 diabetes. This indicates that a mixed nutritional challenge provides important ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4878222/

Two- and Four-Hour Tests Differ in Capture of C-Peptide ... Mixed-meal tolerance tests (MMTTs) are used in clinical trials to evaluate β-cell function in patients with new-onset type 1 diabetes (1,2).

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/33/NCT03449433/SAP_001.pdf

Statistical Analysis Plan: I8B-MC-ITSL(a) A Mixed Meal ... assessed by the mixed meal tolerance test (MMTT), in patients with T1DM. ... endogenous insulin levels following the MMTT from healthy subjects ...