A Study to Determine Iatrogenic Hyperinsulinemia's Contribution to Insulin Resistance and Endothelial Dysfunction in Type 1 Diabetes

NCT04118374 | Completed Results DMC

• 1 other identifier: 190630
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Diabetes Mellitus, Type 1

Keywords

low carbohydrate diet; hyperinsulinemia; insulin resistance; endothelial dysfunction; vascular health

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

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

Interventions

Standard Carb Diet OTHER

Approximately 50% of caloric intake will come from carbohydrate consumption.

Low Carb Diet then Standard Carb Diet; Standard Carb Diet then Low Carb Diet

Low Carb Diet OTHER

Approximately 25% of caloric intake will come from carbohydrate consumption.

Low Carb Diet then Standard Carb Diet; Standard Carb Diet then Low Carb Diet

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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,

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 40045281 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hyperinsulinism; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Justin M Gregory, MD, MSCI
• Organization: Vanderbilt University Medical Center

metabolism@vumc.org

(615) 322- 7427

Study Officials

• Justin M Gregory, MD, MSCI

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 8, 2019
• Study Start: November 24, 2021
• Primary Completion: June 21, 2024
• Study Completion: June 21, 2024
• Last Updated: October 28, 2025
• Results First Posted: October 28, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

US (1)