The Effect of Type 1 Diabetes on Pan-Arterial Vascular Function and Insulin Sensitivity in Humans
| Status: | Completed |
|---|---|
| Conditions: | Diabetes |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 40 |
| Updated: | 4/21/2016 |
| Start Date: | December 2014 |
| End Date: | June 2015 |
Arterial vascular disease is the major cause of morbidity and mortality for Type 1 diabetic
patients (DM1). Metabolic insulin resistance (metIR), even in the absence of hyperglycemia,
conveys a 1.5 to 3-fold increased CVD risk in the general population. Metabolic Insulin
Resistance (MetIR) has been repeatedly shown to be prevalent in adults and adolescents with
DM1. MetIR in obesity and DM2 are accompanied by vascular insulin resistance (vasIR) which
is characterized by impaired vasodilatory action of insulin on resistance or microvascular
vessels. VasIR has not been systematically studied in DM1. We hypothesize that in young
adults DM1 impairs both baseline and insulin-responsive vascular function throughout the
arterial vasculature.
patients (DM1). Metabolic insulin resistance (metIR), even in the absence of hyperglycemia,
conveys a 1.5 to 3-fold increased CVD risk in the general population. Metabolic Insulin
Resistance (MetIR) has been repeatedly shown to be prevalent in adults and adolescents with
DM1. MetIR in obesity and DM2 are accompanied by vascular insulin resistance (vasIR) which
is characterized by impaired vasodilatory action of insulin on resistance or microvascular
vessels. VasIR has not been systematically studied in DM1. We hypothesize that in young
adults DM1 impairs both baseline and insulin-responsive vascular function throughout the
arterial vasculature.
In our study, 20 healthy control subjects will be compared to 20 DM1 patients (18-40 yrs).
We will assess function in conduit (pulse wave velocity-PWV, flow-mediated dilation-FMD and
augmentation index-AI), resistance (post-ischemic flow velocity-PIFV) and heart and skeletal
muscle microvascular (contrast enhanced ultrasound-CEU) vessels before and after 2 hrs of a
euglycemic insulin clamp.
We will assess function in conduit (pulse wave velocity-PWV, flow-mediated dilation-FMD and
augmentation index-AI), resistance (post-ischemic flow velocity-PIFV) and heart and skeletal
muscle microvascular (contrast enhanced ultrasound-CEU) vessels before and after 2 hrs of a
euglycemic insulin clamp.
Inclusion Criteria:
- Age 18-40
- BMI ≤ 25
- Healthy with no chronic illness (control group only)
- Normal screening labs or no clinically significant values
- DM1 subjects will have been on insulin for at least 5 years and HbA1c <9
Exclusion Criteria:
- First degree relative with Type 1 or 2 Diabetes (for control group only)
- Smoking presently or in the past 6 months
- Medications that affect the vasculature (except ACE or ARB in DM1 subjects, although
they will need to be off these drugs for 2 weeks prior to study).
- Elevated LDL cholesterol > 160
- BP <100/60 or >160/90
- Pulse oximetry <90%
- Pregnant or breastfeeding
- History of cardiovascular disease, cerebral vascular disease, peripheral vascular
disease, liver disease
- Presence of an intracardiac or intrapulmonary shunt (we will screen for this by
auscultation during the physical exam ).
- Known hypersensitivity to perflutren (contained in Definity)
- For DM1 group:
- HbA1c ≥ 9
- Microalbuminuria
- Retinipathy
- Ketoacidosis within the past year.
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