Effect of Postprandial Hyperglycemia on Vasculature in Type 1 Diabetes and Healthy Adults

Type 1 Diabetes Clinical Trial

— WBH001  

Official title:

Effect of Postprandial Hyperglycemia on Vasculature in Type 1 Diabetes and Healthy Adults

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04730882
• Other study ID #: 200216
• Secondary ID: KL2TR003016
• Status: Active, not recruiting
• Start date: April 6, 2021
• Est. completion date: January 2025

Study information

• Verified date: December 2023
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To the investigator's knowledge, there are no data available in the current literature regarding the acute effects of postprandial hyperglycemia and insulin timing on myocardial perfusion in people with type 1 diabetes (T1D). Observational studies using CEU in type 2 diabetes demonstrate that postprandial hyperglycemia determines myocardial perfusion defects. The investigator hypothesizes that the combination of postprandial hyperglycemia and insulin increases pulse wave velocity (i.e., aortic stiffness) and myocardial vasoconstriction, thereby reducing myocardial perfusion in T1D when compared to healthy controls. Furthermore, the investigator hypothesizes in T1D that dosing insulin before meal intake will ameliorate these cardiovascular defects.

Description:

The investigator will compare 17 T1D and 17 age-, sex-, and BMI-matched healthy controls (18-35 yrs) measuring pulse wave velocity (PWV), flow-mediated dilation (FMD) and myocardial perfusion (contrast enhanced ultrasound [CEU]) before and 2 hours after ingesting a mixed meal (40% of each subject's daily estimated caloric need, with 50%, 30%, 20% from carbohydrates, fat and protein, respectively).

T1D participants will have 2 study admissions:

A) injection of insulin 15 minutes before ingesting a mixed meal. B) injection of insulin 15 min after ingesting a mixed meal.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 36
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Healthy with no chronic illness

• Age 18-35 years

• BMI = 30 (wt kg/ht m2)

• Normal screening labs or no clinically significant values

• T1D participants must have T1D based on WHO diagnostic criteria for > 1 year

• A fasting plasma glucose level >126 mg/dl (7.0 mmol/l)

• A casual plasma glucose >200 mg/dl (11.1 mmol/l)

• In the absence of unequivocal hyperglycemia, the diagnosis must be confirmed on a subsequent day.

• Subjects using sensor-augmented insulin pump therapy and/or artificial pancreas (closed loop system) will be included

Exclusion Criteria:

• • Smoking presently or have quit < 2 years.

• BP >140/90 mmHg

• BMI >30 (wt kg/ht m2)

• Pulse oximetry <90%

• Elevated LDL cholesterol > 160 mg/dl

• HbA1c = 9 %

• Use of statins, calcium channel blocker, ACE, ARB, nitrates, alpha-beta blockers or diuretics

• History of cardiac, cerebrovascular, gastrointestinal, liver, renal decease or cancer

• Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam by PI).

• Retinopathy (beyond mild non proliferative retinopathy)

• Urine albumin/creatinine ratio > 300 mg per g

• Pregnant or breastfeeding.

• Known hypersensitivity to perflutren (contained in Definity

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hyperglycemia
• Hyperglycemia, Postprandial
• Type 1 Diabetes

Intervention

Dietary Supplement:
• Mixed Meal
the meal will be 40% of each subject's daily estimated caloric need, with 50%, 30%, 20% from carbohydrates, fat and protein, respectively

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
University of Virginia	National Center for Advancing Translational Sciences (NCATS)

Country where clinical trial is conducted

United States, 

References & Publications (72)

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Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myocardial Microvascular Perfusion (measured by contrast-enhanced ultrasound)	Measurement of change in myocardial microvascular perfusion	baseline and 2 hours after a meal
Secondary	Skeletal Muscle Microvascular Perfusion (measured by contrast-enhanced ultrasound)	Measurement of change in microvascular perfusion of skeletal muscle	baseline and 2 hours after a meal
Secondary	Flow Mediated Dilation	Vascular measure of change in conduit artery stiffness	baseline and 2 hours after a meal
Secondary	Pulse Wave Velocity ( PWV)	Measurement of change in central artery stiffness	baseline and 2 hours after a meal
Secondary	Tumor Necrosis Factor-Alpha (TNF-alpha)	Inflammatory biomarker (plasma sample) specific specific to patients with type 1 diabetes	baseline and 2 hours after a meal
Secondary	Interleukin 6 (IL-6)	Inflammatory biomarker (plasma sample) specific specific to patients with type 1 diabetes	baseline and 2 hours after a meal
Secondary	high sensitivity C-reactive protein (hsCRP)	Inflammatory biomarker (plasma sample) specific specific to patients with type 1 diabetes	baseline and 2 hours after a meal
Secondary	Intercellular Adhesion Molecule 1 (ICAM-1)	Biomarker (plasma sample) of endothelial dysfunction	baseline and 2 hours after a meal
Secondary	E-selectin	Biomarker (plasma sample) of endothelial dysfunction	baseline and 2 hours after a meal