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

Completed

• Conditions: Hyperglycemia, Postprandial; Type 1 Diabetes
• Interventions: Dietary Supplement: Mixed Meal

• Registration Number: NCT04730882
• Lead Sponsor: University of Virginia

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2021-01-25
• Study First Submitted QC: 2021-01-28
• Study First Posted: 2021-01-29
• Study Start: 2021-04-06
• Primary Completion: 2024-10-18
• Study Completion: 2024-10-18
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy Control	Mixed Meal	Healthy subjects 18-35 years of age
Type 1 Diabetes	Mixed Meal	People with type 1 diabetes (18-35 yrs) who have type 1 diabetes based on WHO diagnostic criteria for \> 1 year

Primary Outcome Measures

Name	Time	Method
Myocardial Microvascular Perfusion (measured by contrast-enhanced ultrasound)	baseline and 2 hours after a meal	Measurement of change in myocardial microvascular perfusion

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States