Impact of Obesity on Microvascular Insulin Action and Cardiorespiratory Fitness in Type 1 Diabetes

Inclusion Criteria:

* • Male or female ≥21 and ≤50 years old

  * For persons with T1D: Disease duration ≥ 5 years and HbA1c ≤ 8.5% on multiple daily insulin injection or insulin pump
  * Body mass index: ≥19 and ≤27 kg/m2 for control and T1D, ≥30 and ≤40 kg/m2 (27.5 to 37.5 for Asian Americans) for obesity and T1D + obesity. BMI is limited to ≤40 kg/m2 (37.5 for Asian Americans) for easier vascular access and cardiac imaging.
  * Stable use of non-insulin medications for over 6 months other than estrogen/progesterone containing medications which must be discontinued at least 3 months prior to the study (intrauterine devices may be continued due to limited systemic absorption)

Exclusion Criteria:

* • Acute or chronic disease other than T1D or obesity

  * History of microvascular or macrovascular diabetes complications
  * History of diabetic ketoacidosis in the past 24 months
  * History of hypoglycemia unawareness
  * Recently active (\>20 min of moderate/high intensity exercise, 2 times/week)
  * Subjects who are smokers or who have quit smoking \<5 years
  * Subjects with hypertriglyceridemia (\>400 mg/dl)
  * Current use of vasoactive medications (i.e. calcium channel blockers, angiotensin-converting enzyme or renin inhibitors, angiotensin-receptor blockers, nitrates, alpha- or beta-blockers, or diuretics).
  * Females taking oral contraceptives in the past 3 months
  * Subjects with a history of significant metabolic, cardiac, cerebrovascular, hematological, pulmonary, gastrointestinal, liver, renal, or endocrine disease or malignancy
  * Pregnant (as evidenced by positive pregnancy test) or nursing women
  * Musculoskeletal condition preventing participation in exercise testing or exercise training
  * History of gastroparesis
  * Pulse oximetry \<90%