Type 1 Diabetes, Hyperglycemia, Postprandial
Conditions
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.
Interventions
DIETARY_SUPPLEMENTMixed Meal
the meal will be 40% of each subject's daily estimated caloric need, with 50%, 30%, 20% from carbohydrates, fat and protein, respectively
Sponsors
National Center for Advancing Translational Sciences (NCATS)
University of Virginia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial Microvascular Perfusion (measured by contrast-enhanced ultrasound) | baseline and 2 hours after a meal | Measurement of change in myocardial microvascular perfusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Flow Mediated Dilation | baseline and 2 hours after a meal | Vascular measure of change in conduit artery stiffness |
| Pulse Wave Velocity ( PWV) | baseline and 2 hours after a meal | Measurement of change in central 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 |
| 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 |
| 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 |
| Intercellular Adhesion Molecule 1 (ICAM-1) | baseline and 2 hours after a meal | Biomarker (plasma sample) of endothelial dysfunction |
| E-selectin | baseline and 2 hours after a meal | Biomarker (plasma sample) of endothelial dysfunction |
| Interleukin 6 (IL-6) | baseline and 2 hours after a meal | Inflammatory biomarker (plasma sample) specific specific to patients with type 1 diabetes |
Countries
United States
Outcome results
None listed