PK/PD Study of U-500 Regular Insulin
Condition: Type 2 Diabetes; Insulin Resistance; High Insulin Requirements
MeSH terms: Diabetes Mellitus, Type 2; Insulin Resistance; Hyperinsulinism
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to learn more about how U500 regular insulin can be effectively
      be used to treat type 2 diabetes. Most insulin treated patients with type 2 diabetes take
      U100 insulin, but if they require large doses (such as >150 units a day) they may experience
      pain at this site of injection and the absorption of the insulin is unpredictable, thereby
      leading to poor glucose control. To overcome these problems, doctors sometimes switch to a
      more concentrated form of insulin called U500 insulin. U500 is five times as concentrated as
      U100 insulin and therefore delivers an equivalent dose of insulin in much lesser volume.
      However, how to best use U-500 insulin is not certain. The investigators are not really sure
      how long a given dose is effective in patients who require large doses (>150 units of U100
      insulin), so are not sure of how often the drug should be administered. In this study, the
      investigators will determine how effective two different doses of U-500 regular insulin (100
      U and 200 U) are in lowering blood sugar and how long these two doses last. This information
      will help doctors develop better treatment plans for patients with type 2 diabetes.
    

Detailed description: 
      How the Study is performed:

      If you agree to participate, you will be given the chance to come to the Masonic Clinical
      Research Unit (MCRU) at the University of Minnesota for a tour of the facility in the days
      before the actual experiment. While at the MCRU, one of the investigators will talk with you
      about the study and provide you with information about the experiments.

      During the week before the study, you will be asked to hold oral or injectable non-insulin
      medicines used to treat diabetes for 1 week prior to the study and to avoid exercise 48 hours
      prior to the study. During this time you will be asked to monitor your blood sugars and call
      the investigators for help in managing your sugars if they go outside of the target
      recommended by your doctor.

      On night before the study starts, you will be asked to come to Masonic Clinical Research Unit
      (MCRU) after dinner (between 8-10 PM). Upon your arrival two catheters will be placed in the
      arms to establish intravenous access. One will be used for subsequent blood sampling and the
      other will be used for infusion. We will administer intravenous insulin as necessary to
      maintain blood glucose between 100-150 mg/dL overnight. Blood sugars will be obtained every
      15-60 minutes overnight to ensure the glucose remains at target. At 7 AM the next morning,
      the intravenous insulin will be stopped. The study will the start when by giving you a dose
      of either 100 or 200 units of U-500 regular insulin subcutaneously in random order (like a
      flip of a coin). Since insulin drops the blood sugar, we will also be ready to start an
      intravenous infusion of glucose to maintain your blood sugars at 100 mg/dl. To keep your
      sugar at this target, blood will be collected every 15-60 minutes to measure blood sugar and
      the information will be used by the investigators to figure out how much glucose to give you.
      We will continue to measure blood glucose until you can maintain blood glucose without a
      glucose infusion for at least 10 hours or start to experience hyperglycemia (BG > 150 mg/dl)
      for two hours after discontinuation of the glucose infusion. At that point, the catheters
      will be removed and you will be discharged to home. During your stay at the MCRU,
      carbohydrate free meals will be provided starting at noon and continued at traditional
      mealtimes thereafter for the duration of the glucose infusion. Non-caloric decaffeinated
      beverages will be available as needed. At the completion of the study you will be told to
      resume your usual diabetes medications.

      Two to four weeks later, you will be asked to once again hold oral or injectable non-insulin
      medicines used to treat diabetes for 1 week prior to the second part of the study and to
      avoid exercise 48 hours prior to the study. During this time you will be again asked to
      monitor your blood sugars and call the investigators for help in managing your sugars if they
      go outside of the target recommended by your doctor. On night before the second part of the
      study starts, you will be asked to come to Masonic Clinical Research Unit (MCRU) after
      dinner. Intravenous lines will again be placed, intravenous insulin will again be given
      overnight to keep your blood sugar between 100-150 mg/dl, and in the morning you will be
      given the dose of U500 regular insulin you did not receive during the first visit. Your blood
      sugar will then be maintained at 100 mg/dl by the infusion of glucose. We will continue to
      measure blood glucose every 15-60 minutes until you can maintain blood glucose without a
      glucose infusion for at least 10 hours or start to experience hyperglycemia (BG > 150 mg/dl)
      for two hours after discontinuation of the glucose infusion. You will be fed the same diet as
      during your first visit and will be told to resume your diabetes medications at the time we
      send you home.
    

Intervention name(s): U-500 insulin, 100 syringe units; U-500 insulin, 200 syringe units
Intervention type(s): Drug; Drug
Intervention description(s): Subjects are randomized to receive 100 syringe units of U-500 insulin. Subjects will receive opposite treatment after 4-8 weeks.; Subjects are randomized to receive 200 syringe units of U-500 insulin. Subjects will receive opposite treatment after 4-8 weeks.
Other intervention name(s): Highly concentrated regular insulin; Highly concentrated regular insulin
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Type 2 diabetes; Insulin resistance; High insulin requirements; U 500