The Effect of Type 1 Diabetes on Pan-Arterial Vascular Function and Insulin Sensitivity in Humans
The Effect of Type 1 Diabetes on Pan-Arterial Vascular Function and Insulin Sensitivity in Humans
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.
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.
Inclusion Criteria:
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: