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

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

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.

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.

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