WBH001: Effect of Postprandial Hyperglycemia on Vasculature in DM1 and Healthy Adults
Study Details
Study Description
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 DM1. Observational studies using CEU in DM2 subjects 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 DM1 when compared to healthy controls. Furthermore, the investigator hypothesizes in DM1, that dosing insulin before meal intake will ameliorate these cardiovascular defects.
Condition or Disease | Intervention/Treatment | Phase |
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Detailed Description
The investigator will compare 16 DM1 and 16 Healthy control subjects( 18-35 yrs) measuring pulse wave velocity ( PWV), augmentation index ( AI), 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).
DM1 subjects will have 2 study admissions:
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DM1 subjects will have an injection of insulin 15 minutes before ingesting a mixed meal.
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DM1 subjects will have an injection of insulin 15 min after ingesting a meal .
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Healthy Control Healthy subjects 18-35 years of age |
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
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DM1 DM1 subjects (18-35 yrs) have DM1 based on WHO diagnostic criteria for > 1 year |
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
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Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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
- Interleukin 6 (IL-6) [baseline and 2 hours after a meal]
Inflammatory biomarker (plasma sample) specific specific to patients with type 1 diabetes
- 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
Other Outcome Measures
- LY6C hi monocyte [baseline and 2 hours after a meal]
This is an exploratory outcome examining a peripheral blood mononuclear cell known to be inflammatory in transient hyperglycemia
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy with no chronic illness
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Age 18-35 years
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BMI ≤ 30 (wt kg/ht m2)
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Normal screening labs or no clinically significant values
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DM1 subjects have DM1 based on WHO diagnostic criteria for > 1 year
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A fasting plasma glucose level >126 mg/dl (7.0 mmol/l)
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A casual plasma glucose >200 mg/dl (11.1 mmol/l)
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In the absence of unequivocal hyperglycemia, the diagnosis must be confirmed on a subsequent day.
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Subjects using sensor-augmented insulin pump therapy and/or artificial pancreas (closed loop system) will be included
Exclusion Criteria:
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• Smoking presently or have quit < 2 years.
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BP >140/90 mmHg
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BMI >30 (wt kg/ht m2)
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Pulse oximetry <90%
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Elevated LDL cholesterol > 160 mg/dl
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HbA1c ≥ 9 %
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Use of statins, calcium channel blocker, ACE, ARB, nitrates, alpha-beta blockers or diuretics
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History of cardiac, cerebrovascular, gastrointestinal, liver, renal decease or cancer
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Presence of an intracardiac or intrapulmonary shunt (we will screen for this by auscultation during the physical exam by PI).
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Retinopathy (beyond mild non proliferative retinopathy)
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Urine albumin/creatinine ratio > 300 mg per g
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Pregnant or breastfeeding.
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Known hypersensitivity to perflutren (contained in Definity
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | University of Virginia | Charlottesville | Virginia | United States | 22906 |
Sponsors and Collaborators
- University of Virginia
Investigators
- Principal Investigator: William Horton, MD, University of Virginia, Department of Endocrinology
- Study Chair: Zhenqi Liu, MD, University of Virginia, Department of Endocrinology
Study Documents (Full-Text)
None provided.More Information
Publications
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