Enhancement of Cerebral Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Intranasal insulin; Placebo
Intervention description: The acute effects of a single 40-IU dose of intranasal insulin; The acute effects of intranasal sterile saline.
Intervention MeSH terms: Insulin
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 30.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: diabetes, blood flow, brain perfusion, cognitive function

Summary:

      Our goal is to determine the acute effects of intranasal insulin on regional perfusion and
      cognition of older adults. We propose a pilot study to examine the effect of a single dose of
      intranasal insulin on regional vasoreactivity and cognitive functions in 30 subjects with
      T2DM and 30 healthy controls >50 years old using a double blinded, placebo-controlled,
      cross-over design.

      Hypothesis 1: Intranasal insulin improves acutely regional perfusion and vasoreactivity in
      older patients with T2DM as compared with placebo and compared with the control group.

      Hypothesis 2: Intranasal insulin improves cognitive functioning including attention, memory
      and executive function in diabetic patients as compared with placebo and compared with
      control group.
    

Eligibility criteria:

        Inclusion Criteria:

        Diabetes group:

          -  30 men and women aged >50 years old diagnosed with T2DM and treated > 5 years with
             oral agents

          -  Diabetes severity will be assessed from diabetes duration, hemoglobin A1C, and fasting
             glucose levels.

        Control group:

          -  30 healthy men and women aged >50 years selected to have the same age and sex
             distributions as the diabetic subjects

          -  Normotensive, not treated for any systemic disease, and have normal fasting blood
             glucose.

        Exclusion Criteria:

          -  Type 1 Diabetes Mellitus

          -  History of severe hypoglycemia or hypoglycemic episode during home baseline monitoring

          -  Positive stress test for CAD or other ischemic conditions

          -  Carotid stenosis > 50% by medical history

          -  History of a clinically documented stroke

          -  Treatment with any medications administered intranasally including intranasal steroids

          -  Any previous adverse or allergic reactions to insulin

          -  Acute or unstable medical condition including Myocardial infarction or major illness
             and surgery within six months

          -  Liver or renal failure or transplant

          -  Uncontrolled hypertension (systolic BP >180 and/or diastolic BP >100 mm Hg or subjects
             taking more than 3 antihypertensive medications)

          -  Seizure disorders

          -  Malignant tumors

          -  Clinical dementia (by history) or inability to follow details of the protocol(MMSE
             (Mini Mental Status Exam) score (≥3 points below the Comparative Normal Value for the
             subject's age group and education level, or ≤ 24)

          -  Current recreational drug or alcohol abuse

          -  Morbid obesity (BMI >40)

          -  Inability to obtain permission for participation from the primary care physician

          -  Transcranial Doppler (TCD) exclusion criterion - poor insonation window and TCD signal

          -  MR exclusion criteria - any metal or bioimplants not compatible with 3 Tesla MRI and
             claustrophobia

          -  Clinically significant and movement limiting hip, knee and/or back disorders or
             injury, and rheumatoid arthritis