Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The investigators will test the hypothesis that reducing insulin doses using a low carbohydrate diet (LCD) will be associated with with improved insulin sensitivity (Aim 1) and blood vessel health (Aim 2).
Insulin resistance (IR) is consistently found in patients with type 1 diabetes (T1DM) and pathophysiologically links T1DM with atherosclerotic disease. IR and nascent atherosclerosis, as characterized by endothelial dysfunction, are present early in T1DM. Although atherosclerosis leads to cardiovascular disease (CVD)-the predominant cause of death in T1DM-the early cardiometabolic processes driving atherosclerosis are not currently well-characterized. My overarching hypothesis is that IR and endothelial dysfunction in T1DM are, in part, iatrogenic, occurring as a function of nonphysiologic insulin delivery.
Previous research shows IR in T1DM is closely related to iatrogenic hyperinsulinemia. Iatrogenic hyperinsulinemia in T1DM results from injecting insulin into subcutaneous tissue rather than delivering insulin more physiologically into the hepatic portal vein. Hyperinsulinemia, per se, is closely linked with IR and independently predicts CVD in diabetic and nondiabetic populations. Thus, peripheral insulin delivery brings about unintended adverse cardiometabolic consequences in T1DM. The investigators propose a practical intervention to diminish iatrogenic hyperinsulinemia and thereby mitigate CVD risk. The investigators hypothesize that a reduction in iatrogenic hyperinsulinemia brought about by a low carbohydrate diet (LCD) will independently correlate with improved insulin sensitivity (Aim 1) and endothelial function (Aim 2).
In this pilot study, the investigators will mechanistically dissect the contribution of iatrogenic hyperinsulinemia to IR and endothelial dysfunction in 8 adults with T1DM using a crossover study of LCD vs. standard carbohydrate diet (SCD) to experimentally modify hyperinsulinemia. The investigators will quantify insulin sensitivity using hyperinsulinemic, euglycemic clamps and measure endothelium-dependent flow mediated vasodilation using high-resolution ultrasound.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard Carb Diet then Low Carb Diet | Experimental |
| |
| Low Carb Diet then Standard Carb Diet | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard Carb Diet | Other | Approximately 50% of caloric intake will come from carbohydrate consumption. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Insulin Sensitivity Assessed as Glucose Infusion Rates | Participants completed both a one-week RCD and a one-week SCD, separated by a three-week washout. After each intervention, we measured insulin sensitivity using a hyperinsulinemic-euglycemic clamp.To express GIR in mg of glucose per kg of fat-free mass per minute (mg/kg FFM/min), we divided the dextrose infusion rate by the fat-free mass determined by DEXA. Insulin sensitivity showed no significant difference between diets. GIR was 8.1 mg/kg FFM/min after the RCD and 8.6 mg/kg FFM/min after the SCD. | week 1 and week 5 |
Not provided
Not provided
Inclusion Criteria:
Exclusion Criteria:
medications
other:
Additional exclusion criteria for T1DM subjects
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Justin M Gregory, MD, MSCI | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40045281 | Result | Gregory JM, Smith TJ, Duffus SH, Brooks D, Akbar MN, Huntley MA, Gottlieb JA, LeStourgeon LM, Wilson CS, Beckman JA, Cherrington AD. A one-week reduced-carbohydrate diet to mitigate iatrogenic peripheral hyperinsulinemia does not improve insulin sensitivity or endothelial function in a randomized, crossover trial in patients with type 1 diabetes. Cardiovasc Diabetol. 2025 Mar 5;24(1):107. doi: 10.1186/s12933-025-02658-z. | |
| 41882799 |
Not provided
Not provided
The datasets generated during and/or analyzed during the current study can be available from the corresponding author upon reasonable request. Data sets can be made available beginning 3 months and ending 5 years following article publication. No applicable resources have yet been generated or analyzed during the current study.
Not provided
Not provided
Not provided
In the full study, 14 participants enrolled and completed the screening visit. Two did not proceed past the run-in period due to scheduling conflicts and inconsistent nutrition logging.
14 patients were screened for eligibility between November 2021 and March 2024. We recruited adults with type 1 diabetes (age 18-60 years, BMI 18-33 kg/m2, HbA1c 5.9-9.0%) from the Vanderbilt Eskind Diabetes Clinic and community sources in Nashville, TN.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Standard Carb Diet then Low Carb Diet | Standard Carb Diet: Approximately 50% of caloric intake will come from carbohydrate consumption. Low Carb Diet: Approximately 25% of caloric intake will come from carbohydrate consumption. |
| FG001 | Low Carb Diet then Standard Carb Diet |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Intervention (7 days) |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 29, 2021 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Low Carb Diet | Other | Approximately 25% of caloric intake will come from carbohydrate consumption. |
|
| Derived |
| Akbar MN, Smith TJ, Chinnarasu S, Welch W, Zuofei W, Litts B, LeStourgeon LM, Saleem M, Khan MM, Kirabo A, Gregory JM. A one-week reduced-carbohydrate diet lowers insulin requirements and shifts the IGF axis with no detectable short-term change in endothelial function in a randomized, crossover trial of adults with type 1 diabetes. Cardiovasc Diabetol Endocrinol Rep. 2026 Mar 26;12(1):13. doi: 10.1186/s40842-026-00276-6. |
Standard Carb Diet: Approximately 50% of caloric intake will come from carbohydrate consumption. Low Carb Diet: Approximately 25% of caloric intake will come from carbohydrate consumption. |
| COMPLETED |
|
| NOT COMPLETED |
|
| Washout Period (21 days) |
|
| Second Intervention (7 days) |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Standard Carb Diet: Approximately 50% of caloric intake will come from carbohydrate consumption. Low Carb Diet: Approximately 25% of caloric intake will come from carbohydrate consumption. then all study participants crossed over to Low Carb Diet: Approximately 25% of caloric intake will come from carbohydrate consumption. Standard Carb Diet: Approximately 50% of caloric intake will come from carbohydrate consumption. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||
| BMI | Median | Inter-Quartile Range | kg/m^2 |
| |||||||||||||||||
| Weight | Median | Inter-Quartile Range | kg |
| |||||||||||||||||
| Height | Median | Inter-Quartile Range | m |
| |||||||||||||||||
| Waist-to-hip ratio | Median | Inter-Quartile Range | ratio |
| |||||||||||||||||
| HbA1c | Median | Inter-Quartile Range | percentage of HbA1c |
| |||||||||||||||||
| HbA1c | Median | Inter-Quartile Range | mmol/mol |
| |||||||||||||||||
| Type 1 diabetes duration | Median | Inter-Quartile Range | years |
| |||||||||||||||||
| Systolic blood pressure | Median | Inter-Quartile Range | mmHg |
| |||||||||||||||||
| Diastolic blood pressure | Median | Inter-Quartile Range | mmHg |
| |||||||||||||||||
| Heart rate | Median | Inter-Quartile Range | bpm |
| |||||||||||||||||
| Insulin analog used | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Insulin Sensitivity Assessed as Glucose Infusion Rates | Participants completed both a one-week RCD and a one-week SCD, separated by a three-week washout. After each intervention, we measured insulin sensitivity using a hyperinsulinemic-euglycemic clamp.To express GIR in mg of glucose per kg of fat-free mass per minute (mg/kg FFM/min), we divided the dextrose infusion rate by the fat-free mass determined by DEXA. Insulin sensitivity showed no significant difference between diets. GIR was 8.1 mg/kg FFM/min after the RCD and 8.6 mg/kg FFM/min after the SCD. | 12 participants received both interventions in this crossover study and were included in the analysis. | Posted | Median | Inter-Quartile Range | mg/kg FFM/min | week 1 and week 5 |
|
|
|
|
through study completion, an average of 1 year
Participants self-report
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard Carb Diet | Standard Carb Diet: Approximately 50% of caloric intake will come from carbohydrate consumption. | 0 | 12 | 0 | 12 | 2 | 12 |
| EG001 | Low Carb Diet | Low Carb Diet: Approximately 25% of caloric intake will come from carbohydrate consumption. | 0 | 12 | 0 | 12 | 1 | 12 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Shakiness | Nervous system disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Justin M Gregory, MD, MSCI | Vanderbilt University Medical Center | (615) 322- 7427 | metabolism@vumc.org |
| Jul 3, 2025 |
| Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 14, 2022 | Jun 7, 2023 | ICF_000.pdf |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D006946 | Hyperinsulinism |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Fast-acting insulin aspart |
|