Diabetes Mellitus, Type 1NCT04118374
A Study to Determine Iatrogenic Hyperinsulinemia's Contribution to Insulin Resistance and Endothelial Dysfunction in Type 1 Diabetes
A study testing Standard Carb Diet and Low Carb Diet in people with Diabetes Mellitus, Type 1, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- Standard Carb Diet and Low Carb Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Nov 2021to 21 Jun 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age: 18-60
- HbA1c: 5.6-9.0%
- Insulin delivery: must be on an insulin pump
- Glucose Monitor: must use a continuous glucose monitor (CGM)
- BMI 18-33 kg/m^2
- Body Mass >/= 50 kg ( 110 lbs)
Who cannot join
- severe hypoglycemia : >/= 1 episode in the past 3 months
- diabetes comorbidities (>= 1 trip to emergency department for poor glucose control in the past 6 months,
- New York Heart Association Class II-IV cardiac functional status
- SBP > 140 and DBP > 100 mmHg,
- eGFR by MDRD equation of <60 mL/min/1.73m^2
- AST or ALT > 2.5 times the upper limit of normal
Show all 27Show fewer
- HCT <35%
- medications
- any antioxidant vitamin supplement (<2 weeks before STUDY visit)
- any systemic glucocorticoid
- any antipsychotic
- atenolol, metoprolol, propranolol
- niacin
- any thiazide diuretic
- any OCP with > 35 mcg ethinyl estradiol,
- growth hormone
- any immunosuppressant
- any antihypertensive
- any antihyperlipidemic
- other:
- pregnancy
- Tanner stage < 5
- peri or postmenopausal woman
- active smoker
- gluten-free diet requirement
- Additional exclusion criteria for T1DM subjects
- any diabetes medication except insulin
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
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).
Read the detailed description
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.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- Standard Carb Diet, Low Carb Diet
- Keywords
- low carbohydrate diet, hyperinsulinemia, insulin resistance, endothelial dysfunction, vascular health
- Medical subject headings
- Diabetes Mellitus, Type 1, Hyperinsulinism, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard Carb DietOther
Approximately 50% of caloric intake will come from carbohydrate consumption.
Low Carb DietOther
Approximately 25% of caloric intake will come from carbohydrate consumption.
| Study group | Role | What they receive |
|---|---|---|
| Standard Carb Diet then Low Carb Diet | Experimental | Not described Receives: Other: Standard Carb Diet; Other: Low Carb Diet |
| Low Carb Diet then Standard Carb Diet | Experimental | Not described Receives: Other: Standard Carb Diet; Other: Low Carb Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: week 1 and week 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2019
- Study start24 Nov 2021
- Primary completion21 Jun 2024
- Study completion21 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Justin Gregory, Vanderbilt University Medical Center
- Investigators
- Justin M Gregory, MD, MSCI, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04118374
- Sponsor's protocol ID
- 190630
- Status last verified
- Sep 2025
- First submitted
- 2 Oct 2019
- Last updated
- 28 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 40045281Akbar 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.
PubMed 41882799
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Determine Iatrogenic Hyperinsulinemia's Contribution to Insulin Resistance and Endothelial Dysfunction in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT04118374
- Acronym / sponsor ID
- 190630
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- low carbohydrate diet, hyperinsulinemia, insulin resistance, endothelial dysfunction, vascular health
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 24 Nov 2021 (actual)
- Primary completion
- 21 Jun 2024 (actual)
- Study completion
- 21 Jun 2024 (actual)
- First posted
- 8 Oct 2019 (actual)
- Results
- Posted 28 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Carb Diet then Low Carb Diet | Experimental | Other: Standard Carb Diet, Other: Low Carb Diet |
| Low Carb Diet then Standard Carb Diet | Experimental | Other: Standard Carb Diet, Other: Low Carb Diet |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Age: 18-60
- HbA1c: 5.6-9.0%
- Insulin delivery: must be on an insulin pump
- Glucose Monitor: must use a continuous glucose monitor (CGM)
- BMI 18-33 kg/m^2
Key exclusion criteria (27 listed)
- severe hypoglycemia : >/= 1 episode in the past 3 months
- diabetes comorbidities (>= 1 trip to emergency department for poor glucose control in the past 6 months,
- New York Heart Association Class II-IV cardiac functional status
- SBP > 140 and DBP > 100 mmHg,
- eGFR by MDRD equation of <60 mL/min/1.73m^2
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard Carb DietApproximately 50% of caloric intake will come from carbohydrate consumption. | Other | Low Carb Diet then Standard Carb Diet, Standard Carb Diet then Low Carb Diet |
| Low Carb DietApproximately 25% of caloric intake will come from carbohydrate consumption. | Other | Low Carb Diet then Standard Carb Diet, Standard Carb Diet then Low Carb Diet |
Primary outcome
Change in Insulin Sensitivity Assessed as Glucose Infusion Rates
Time frame: week 1 and week 5
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 40045281Gregory 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.
- Derived from this study: PubMed 41882799Akbar 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Justin M Gregory, MD, MSCI principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standard Carb Diet and Low Carb Diet in people with Diabetes Mellitus, Type 1, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Insulin Sensitivity Assessed as Glucose Infusion Rates (time frame: week 1 and week 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04118374, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2025.