Clinical trial NCT04730882: Effect of Postprandial Hyperglycemia on Vasculature in Type 1 Diabetes and Healthy Adults
Official title: Effect of Postprandial Hyperglycemia on Vasculature in Type 1 Diabetes and Healthy Adults
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 1 Diabetes
Hyperglycemia, Postprandial
Lead sponsor: University of Virginia
Sponsor class: OTHER
Collaborators: name: National Center for Advancing Translational Sciences (NCATS)
First posted: 2021-01-29
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 17 Healthy controls and 17 participants with T1D

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.

Eligibility criteria: 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

Primary outcomes:
measure: Myocardial Microvascular Perfusion (measured by contrast-enhanced ultrasound)
timeFrame: baseline and 2 hours after a meal
Secondary outcomes:
measure: Skeletal Muscle Microvascular Perfusion (measured by contrast-enhanced ultrasound)
timeFrame: baseline and 2 hours after a meal
measure: Flow Mediated Dilation
timeFrame: baseline and 2 hours after a meal
measure: Pulse Wave Velocity ( PWV)
timeFrame: baseline and 2 hours after a meal
measure: Tumor Necrosis Factor-Alpha (TNF-alpha)
timeFrame: baseline and 2 hours after a meal
measure: Interleukin 6 (IL-6)
timeFrame: baseline and 2 hours after a meal
measure: high sensitivity C-reactive protein (hsCRP)
timeFrame: baseline and 2 hours after a meal
measure: Intercellular Adhesion Molecule 1 (ICAM-1)
timeFrame: baseline and 2 hours after a meal
measure: E-selectin
timeFrame: baseline and 2 hours after a meal
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia, Department of Endocrinology
name: William Horton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia, Department of Endocrinology
name: Zhenqi Liu, MD
role: STUDY_CHAIR
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