Diabetes Mellitus, Type 1
Conditions
Keywords
low carbohydrate diet, hyperinsulinemia, insulin resistance, endothelial dysfunction, vascular health
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).
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.
Interventions
OTHERStandard Carb Diet
Approximately 50% of caloric intake will come from carbohydrate consumption.
OTHERLow Carb Diet
Approximately 25% of caloric intake will come from carbohydrate consumption.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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, * growth hormone * any immunosuppressant * any antihypertensive * any antihyperlipidemic other: * pregnancy * Tanner stage \< 5 * peri or postmenopausal woman * active smoker * gluten-free diet requirement Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Insulin Sensitivity Assessed as Glucose Infusion Rates | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 33.9 years |
| BMI | 26.5 kg/m^2 |
| Diastolic blood pressure | 82 mmHg |
| HbA1c | 7.1 percentage of HbA1c |
| Heart rate | 65 bpm |
| Height | 1.75 m |
| Insulin analog used Aspart | 5 Participants |
| Insulin analog used Fast-acting insulin aspart | 1 Participants |
| Insulin analog used Lispro | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
| Systolic blood pressure | 120 mmHg |
| Type 1 diabetes duration | 20.5 years |
| Waist-to-hip ratio | 0.83 ratio |
| Weight | 75.3 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 2 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
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.
Time frame: week 1 and week 5
Population: 12 participants received both interventions in this crossover study and were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Carb Diet | Change in Insulin Sensitivity Assessed as Glucose Infusion Rates | 8.6 mg/kg FFM/min |
| Low Carb Diet | Change in Insulin Sensitivity Assessed as Glucose Infusion Rates | 8.1 mg/kg FFM/min |
p-value: <0.0195% CI: [-0.5, 1.8]ANOVA