Meal Timing for Blood Sugar Control

Overseen By Talia Hitt, MD/MPH/MSHP

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Must not be taking: Insulin, Melatonin, others

Disqualifiers: Diabetes, Sleep disorders, Pregnancy, others

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

Compensation: Varies

Number of Visits: 12

70 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed study uses a novel and rigorous randomized cross-over study design in youth (17-23y) with late and non-late chronotype (n=35 per group) to assess the glycemic effect of "aligning" an oral glucose tolerance test (OGTT) or first-meal of day to a subject's chronotype. Both groups will undergo 2 OGTTs (aligned and mis-aligned with chronotype) to compare glucose tolerance and insulin sensitivity within-subject (primary outcome) and between groups (Aim 1). Then, youth will also undergo two standardized meals (aligned and mis-aligned with chronotype) while wearing continuous glucose monitoring to compare post-prandial glucose excursions within-subject and between groups (Aim 2). A pilot Exploratory Aim 3 (n=12 per group) will investigate delayed melatonin patterns under dim-light as a potential pathophysiologic mechanism behind abnormal glucose tolerance in youth with late chronotype on morning OGTTs.

Will I have to stop taking my current medications?

If you are taking medications that affect insulin sensitivity, glucose tolerance, or circadian rhythm, you may need to stop them to participate in this trial.

What data supports the effectiveness of the treatment Timing of OGTT, Timing of Standardized Meal for blood sugar control?

Research shows that the timing of meals and insulin can significantly impact blood sugar levels. For example, taking insulin 15-20 minutes before eating can reduce post-meal blood sugar spikes by about 30% in people with diabetes. Additionally, delaying meals can lead to higher blood sugar levels, highlighting the importance of regular meal timing. ^{1 2 3 4 5}

Is meal timing for blood sugar control safe for humans?

The research articles provided do not contain specific safety data related to meal timing for blood sugar control in humans. ^{5 6 7 8 9}

How does the treatment of meal timing for blood sugar control differ from other treatments for diabetes?

This treatment focuses on the timing of meals and glucose tests to manage blood sugar levels, which is different from traditional diabetes treatments that primarily use medications like insulin or oral drugs. By adjusting when meals and glucose tests occur, it aims to improve blood sugar control through natural body processes rather than relying solely on medication. ^{6 10 11 12 13}

Research Team

Talia Hitt, MD/MPH/MSHP

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for young individuals aged 17-23 with obesity, prediabetes, or diabetes. It's specifically designed to see how their body clock (chronotype) affects their blood sugar control when they take a glucose test or have their first meal of the day at different times.

Inclusion Criteria

Normal sleep duration (average >7 hours of sleep per night)

Social jetlag (difference between weekend and weekday sleep) of < 2 hours

I have gone through puberty.

Exclusion Criteria

Screening high risk for obstructive sleep apnea

I am not on medications that affect insulin sensitivity, glucose tolerance, or my body clock.

I have diabetes, a sleep disorder, a major illness, am pregnant, or have a genetic syndrome.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Cross-over

Participants undergo 2 OGTTs (aligned and mis-aligned with chronotype) to compare glucose tolerance and insulin sensitivity

11 days

Multiple visits for OGTTs on Day 4 and Day 11

Standardized Meal Testing

Participants undergo two standardized meals (aligned and mis-aligned with chronotype) while wearing continuous glucose monitoring

8 days

Continuous monitoring over 8 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Timing of OGTT
• Timing of Standardized Meal

Trial Overview The study is testing if timing an oral glucose tolerance test (OGTT) or the first meal of the day according to a person's natural sleep/wake cycle can affect insulin sensitivity and blood sugar levels in youth. Participants will experience tests both aligned and misaligned with their chronotype.

Participant Groups

Group I: Cohort B - Non-late Chronotype first, then alternate Experimental Treatment 2 Interventions

Sleep onset before 11pm

Group II: Cohort A - Late Chronotype first, then alternate Experimental Treatment 2 Interventions

Sleep onset after 2am

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

DexCom, Inc.

Industry Sponsor

Trials

151

Recruited

35,700+

Kevin Sayer

DexCom, Inc.

Chief Executive Officer since 2015

Bachelor’s and Master’s degrees in Accounting and Information Systems from Brigham Young University

Dr. Shelly Lane

DexCom, Inc.

Chief Medical Officer since 2023

MD from University of California, San Diego

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Lawson Wilkins Pediatric Endocrine Society

Collaborator

Trials

4

Recruited

190+

Findings from Research

Administering a rapid-acting insulin bolus 20 minutes before a meal significantly improves blood glucose control in adolescents and adults with type 1 diabetes, as shown by lower glycemic excursions and peak blood glucose levels.

In a study with 23 participants, the PRE timing of insulin delivery resulted in better post-meal glucose management compared to administering insulin immediately before or after the meal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timing of meal insulin boluses to achieve optimal postprandial glycemic control in patients with type 1 diabetes. Cobry, E., McFann, K., Messer, L., et al.[2022]

Delaying dinner by 1 hour or more significantly increases peak glucose levels and overall glucose fluctuations in healthy young adults, as measured by continuous glucose monitoring devices.

The study highlights the importance of regular meal timing, suggesting that irregular eating habits, like late dinners, can negatively impact glucose control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed dinnertime impairs glucose tolerance in healthy young adults. Nakamura, F., Shimba, Y., Toyonaga, S., et al.[2023]

In a study of 20 well-controlled type 2 diabetes patients, skipping or eating the last meal of the day earlier significantly increased the duration of hypoglycemia, particularly during the night hours from 00:00 to 06:00.

The findings suggest that when adjusting basal insulin doses, it is crucial to consider the timing of the last meal to prevent nighttime hypoglycemia, which may go unnoticed by patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omitting late-night eating may cause hypoglycemia in "well controlled" basal insulin-treated type 2 diabetes. King, AB., Clark, D.[2021]

Administering rapid-acting insulin analogues 15-20 minutes before meals can significantly improve postprandial glucose control in patients with Type 1 diabetes, reducing post-meal glucose levels by approximately 30%.

Taking insulin after meals increases the risk of postprandial hypoglycemia, highlighting the importance of timing in insulin administration for optimal diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal prandial timing of bolus insulin in diabetes management: a review. Slattery, D., Amiel, SA., Choudhary, P.[2022]

In a study of 377 Latin American patients with type 2 diabetes, exenatide taken before breakfast or lunch showed similar effectiveness in lowering HbA1c levels, with both regimens achieving significant reductions of approximately 1.2% and 1.1%, respectively.

The safety profile was comparable for both dosing schedules, with similar rates of hypoglycemia and nausea, indicating that either timing of exenatide administration is a safe option for improving glycemic control in patients who consume a small breakfast.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of exenatide administered before the two largest daily meals of Latin American patients with type 2 diabetes. Forti, A., Garcia, EG., Yu, MB., et al.[2022]

In a study of 100 patients with type 2 diabetes, exenatide was found to be more effective than Humalog Mix25 and oral antidiabetic drugs (OADs) in shifting the peak blood glucose time to an earlier point, which is a positive indicator of improved glucose metabolism.

Exenatide also significantly improved insulin secretion and insulin sensitivity, as evidenced by better insulinogenic index and homeostatic assessment of β-cell function compared to the other treatments, highlighting its superior efficacy in managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shift of Glucose Peak Time During Oral Glucose Tolerance Test is Associated with Changes in Insulin Secretion and Insulin Sensitivity After Therapy with Antidiabetic Drugs in Patients with Type 2 Diabetes. Jiang, Y., Cui, S., Zhang, R., et al.[2021]

In a study involving 35 adults with type 1 diabetes, the fully closed loop (FCL) insulin delivery system with meal anticipation (FCL+) did not significantly improve post-meal blood sugar control compared to the standard FCL system, maintaining similar time in range (TIR) after meals.

Both FCL and FCL+ systems showed a similar or reduced risk of hypoglycemia, indicating that while meal anticipation did not enhance glycemic control, it also did not increase the risk of low blood sugar during meal delays.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Meal Anticipation for Improving Fully Automated Insulin Delivery in Adults With Type 1 Diabetes. Garcia-Tirado, J., Colmegna, P., Villard, O., et al.[2023]

Administering rapid-acting insulin 15 minutes before meals significantly reduces post-meal blood sugar spikes in individuals with type 1 diabetes, as shown in a study with 10 participants.

This timing also allows for more time spent in the target glucose range (3.5-10.0 mmol/l) without increasing the risk of hypoglycemia, making it a safer option for managing blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Premeal injection of rapid-acting insulin reduces postprandial glycemic excursions in type 1 diabetes. Luijf, YM., van Bon, AC., Hoekstra, JB., et al.[2022]

In a study of 4,768 young participants with type 1 diabetes, those who administered insulin before meals had significantly lower HbA1c levels (8.4%) compared to those who took it during or after meals (8.8%), indicating better glycemic control.

Participants who missed at least one insulin dose per week had higher HbA1c levels (9.8%) and were more likely to experience diabetic ketoacidosis (DKA) events (9%) compared to those who rarely missed doses, highlighting the importance of timely insulin administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timing of Meal Insulin and Its Relation to Adherence to Therapy in Type 1 Diabetes. Datye, KA., Boyle, CT., Simmons, J., et al.[2020]

Gastric emptying (GE) significantly influences blood glucose levels during a 75-g oral glucose tolerance test (OGTT), with stronger correlations observed in individuals with impaired glucose tolerance (IGT) and type 2 diabetes (T2D) compared to those with normal glucose tolerance (NGT).

The study found that the relationship between GE and blood glucose levels varies over time, indicating that GE affects glycemic responses differently at 30, 60, and 120 minutes after glucose ingestion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationships of Early And Late Glycemic Responses With Gastric Emptying During An Oral Glucose Tolerance Test. Marathe, CS., Horowitz, M., Trahair, LG., et al.[2015]

The study analyzed insulin levels during an oral glucose tolerance test (oGTT) in 101 adults using three different immunoassays, finding that all assays had comparable sensitivity and precision, but significant differences in insulin levels and sensitivity indices were observed with the AutoDELFIA method compared to the others.

It is important to use assay-specific reference intervals for interpreting insulin levels from oGTT, as factors like body mass index (BMI) and gender significantly influence insulin measurements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assay-dependent variability of serum insulin levels during oral glucose tolerance test: influence on reference intervals for insulin and on cut-off values for insulin sensitivity indices. Werner, M., Tönjes, A., Stumvoll, M., et al.[2016]

A study involving 46 hospitalized diabetic patients with vascular disease showed that a modified meal schedule significantly improved glucose control compared to a traditional feeding schedule, with higher percentages of patients maintaining normal glucose levels after meals.

The modified schedule resulted in better glucose management, with Group I achieving 91% normal levels at breakfast and 86% at snack time, compared to lower percentages in Group II, highlighting the importance of meal timing in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Diet and insulin. Best results with an adjusted schedule]. Martínez Martínez, A., Bonaventura Sans, C., Malet Bonet, M.[2015]

In a study of 551 subjects, the shape of the plasma glucose response during an oral glucose tolerance test (OGTT) was found to vary based on glucose tolerance status and sex, with biphasic responses indicating better metabolic health compared to monophasic responses.

The study suggests that the 'shape index' of glucose response could serve as a valuable screening tool for assessing metabolic health and understanding genetic influences on glucose tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the shape of the glucose curve during an oral glucose tolerance test. Tschritter, O., Fritsche, A., Shirkavand, F., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Timing of meal insulin boluses to achieve optimal postprandial glycemic control in patients with type 1 diabetes. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

Delayed dinnertime impairs glucose tolerance in healthy young adults. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Omitting late-night eating may cause hypoglycemia in "well controlled" basal insulin-treated type 2 diabetes. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Optimal prandial timing of bolus insulin in diabetes management: a review. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of exenatide administered before the two largest daily meals of Latin American patients with type 2 diabetes. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Shift of Glucose Peak Time During Oral Glucose Tolerance Test is Associated with Changes in Insulin Secretion and Insulin Sensitivity After Therapy with Antidiabetic Drugs in Patients with Type 2 Diabetes. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Assessment of Meal Anticipation for Improving Fully Automated Insulin Delivery in Adults With Type 1 Diabetes. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Premeal injection of rapid-acting insulin reduces postprandial glycemic excursions in type 1 diabetes. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Timing of Meal Insulin and Its Relation to Adherence to Therapy in Type 1 Diabetes. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Relationships of Early And Late Glycemic Responses With Gastric Emptying During An Oral Glucose Tolerance Test. [2015]

11. Germany pubmed.ncbi.nlm.nih.gov

Assay-dependent variability of serum insulin levels during oral glucose tolerance test: influence on reference intervals for insulin and on cut-off values for insulin sensitivity indices. [2016]

12. Spain pubmed.ncbi.nlm.nih.gov

[Diet and insulin. Best results with an adjusted schedule]. [2015]

13. United States pubmed.ncbi.nlm.nih.gov

Assessing the shape of the glucose curve during an oral glucose tolerance test. [2022]