Study to Estimate the Effects of Inhaled Versus Intravenous (IV) Infusion of Human Insulin in Subjects With Type 1 Diabetes
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 4

Summary: 
      University of Pittsburgh Medical Center (UPMC) diabetes research physicians are studying the
      action in muscle tissue of "inhaled" insulin (Exubera®) and "infused" (intravenous or IV)
      insulin on blood sugar control in people with type 1 diabetes. Type 1 diabetics often take
      2-4 shots of insulin every day. Exubera may offer an alternative to these insulin injections.
    

Detailed description: 
      A dry powder insulin formulation delivered by an aerosol inhaler has been in clinical
      development for use in types 1 and 2 diabetes mellitus (DM) and just recently (1-27-06)
      received approval from the U.S. Food and Drug Administration (FDA) for the clinical treatment
      of diabetes. Administration of insulin without the need for subcutaneous (SC) injection is an
      attractive alternative for patients with diabetes. There are preclinical and clinical data
      that indicate inhalation of insulin results in a more potent effect on glucose disposal and a
      lower fasting glucose than is attained with equivalent dosing of SC or intravenous (IV)
      insulin. The physiological mechanism(s) are unclear, but occur even when matched for
      pharmacokinetics.

      The current proposal seeks primarily to more fully delineate whether there are physiological
      differences in the metabolic effects of inhaled compared to IV infused insulin, giving IV
      insulin to match the pharmacokinetics (PK) achieved with inhaled insulin.

      There are 3 specific aims:

        1. The first aim is to establish a protocol for matching the PK of inhaled insulin with the
           PK of intravenously infused insulin. An infusion algorithm has been developed and will
           be tested and refined in healthy volunteers (n = 3-5), and will be used for the
           physiological studies (aims) outlined below.

        2. The second aim is to perform Positron Emission Tomography (PET) imaging of [18F]-FDG
           uptake by muscle, following administration of a single dose of inhaled compared to
           infused insulin. Volunteers with type 1 DM (n =12) will be studied, serving as his/her
           within-subject control, under each condition of insulin administration.

           In these type 1 diabetes mellitus (type 1 DM) volunteers, we will test the hypothesis
           that a single dose of inhaled versus infused insulin, matched for arterial
           concentrations, causes greater stimulation of muscle glucose uptake.

        3. The third aim is to determine overnight rates of glucose production and plasma glucose
           after a single pre-dinner dose of inhaled compared to IV infused insulin. The same 12
           volunteers studied for Aim 2 will be studied the evening preceding the PET imaging
           studies and will serve as his/her within-subject control, under each condition of
           insulin administration.
    

Intervention name(s): Exubera
Intervention type(s): Drug
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: type 1 diabetes mellitus; inhaled insulin; Positron Emission Tomography