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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Type 1 Diabetes, Hyperglycemia, Postprandial

Intervention / Treatment
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* Dietary Supplement: Mixed Meal


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Control<br>Healthy subjects 18-35 years of age | Dietary Supplement: Mixed Meal<br>* the meal will be 40% of each subject's daily estimated caloric need, with 50%, 30%, 20% from carbohydrates, fat and protein, respectively<br>|
| Type 1 Diabetes<br>People with type 1 diabetes (18-35 yrs) who have type 1 diabetes based on WHO diagnostic criteria for > 1 year | Dietary Supplement: Mixed Meal<br>* the meal will be 40% of each subject's daily estimated caloric need, with 50%, 30%, 20% from carbohydrates, fat and protein, respectively<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial Microvascular Perfusion (measured by contrast-enhanced ultrasound) | Measurement of change in myocardial microvascular perfusion | baseline and 2 hours after a meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Flow Mediated Dilation | Vascular measure of change in conduit artery stiffness | baseline and 2 hours after a meal | 
| Pulse Wave Velocity ( PWV) | Measurement of change in central artery stiffness | baseline and 2 hours after a meal | 
| 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 | 
| Interleukin 6 (IL-6) | Inflammatory biomarker (plasma sample) specific specific to patients with type 1 diabetes | baseline and 2 hours after a meal | 
| 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 | 
| Intercellular Adhesion Molecule 1 (ICAM-1) | Biomarker (plasma sample) of endothelial dysfunction | baseline and 2 hours after a meal | 
| E-selectin | Biomarker (plasma sample) of endothelial dysfunction | baseline and 2 hours after a meal |