Measurement of Glucose Metabolism in Humans Using Magnetic Resonance at 4 Tesla. Substudy: Hypoglycemia Unawareness
Condition: Type 1 Diabetes; Hypoglycemia Unawareness
MeSH terms: Unconsciousness; Diabetes Mellitus, Type 1; Hypoglycemia
Study type: Observational

Summary: 
      The purpose of this study is to determine whether islet transplantation alters brain glucose
      concentrations in patients with type 1 diabetes, recurrent hypoglycemia, and hypoglycemia
      unawareness when compared to that measured prior to transplant in the same subjects.
    

Detailed description: 
      Individuals with type 1 diabetes and hypoglycemia unawareness who become active islet
      transplant candidates and matched controls will be recruited for participation in this study.
      Subjects will undergo a hyperglycemic clamp with somatostatin before and 6 months after islet
      transplantation. During the clamp study, their brain glucose concentrations will be measured
      by proton magnetic resonance spectroscopy. Following these measurements, subjects will
      undergo a hypoglycemic clamp study to assess their counterregulatory response.

      On the morning of the study subjects will report to the Clinical Research Center in the CMRR
      and be asked to do the following:

        1. All subjects will be asked not to eat anything after midnight on the day before the
           magnet study at the Magnet Center. A small plastic catheter will be placed in a vein in
           each arm for infusion of hormones. A third plastic catheter will be placed in a foot
           vein for measuring blood glucose levels. The foot and distal leg will be placed in a
           heated blanket for the duration of the study to speed up the flow of blood through the
           vein and for easy withdrawing of blood. During the study subjects will receive carefully
           calculated doses of insulin, glucose, potassium phosphate, and somatostatin. These
           substances will be contained in syringes or bags and pumped through intravenous
           catheters placed in the arms. Insulin and somatostatin are hormones that are made
           naturally by the body. Initially we will keep blood sugar at the normal level. The blood
           glucose will then be raised by infusing glucose at a calculated rate. We will maintain
           the high blood sugar concentration for 45 to 120 minutes. This causes no symptoms other
           than a necessity f to pass urine more frequently than normal. The blood glucose infusion
           will then be dropped to allow blood glucose to drop in small steps to the normal glucose
           concentration. We will draw at most 15 oz. of blood during this part of the study.

        2. All subjects will be asked to participate in a second experiment after the magnet study.
           Subjects may chose to perform this part of the study at Yale University. If subjects
           choose to stay at the University Of Minnesota, they will be participating in the second
           experiment either the same day or the day after the first experiment. If done the same
           day, the arm catheters will be left in place for infusion of insulin, potassium
           phosphate, and glucose. A third catheter may be placed in the hand for venous blood
           sampling. This hand will be placed in a warming box to ensure adequate blood flow and
           accurate laboratory results. Blood will be drawn every 5 minutes for measurement of
           glucose and other hormones. The total amount of blood drawn will be about 10
           tablespoons. Insulin will be infused to lower blood sugar level to a level below the
           normal range. It will be maintained at this low level for thirty minutes after which
           time the insulin infusion will be discontinued and the blood sugar level allowed to
           normalize. Subjects will then be given a meal.

        3. Subjects with type 1 diabetes will be asked to spend the night before each study at the
           General Clinical Research Center so that blood glucose values can be maintained between
           80-110 mg/dl. They will be asked to hold insulin doses in the evening before and on the
           morning of the study and insulin will be provided via an intravenous infusion. For those
           subjects with diabetes who chose to undergo all testing at the University of Minnesota,
           they will be followed as inpatients in the GCRC during one to two days of testing.

        4. Following islet transplant subjects will be asked to undergo the magnet study described
           under point #1 above and the hypoglycemia study described under point #3 above at
           approximately 3-9 months after the procedure.
    

Intervention name(s): somatostatin
Intervention type(s): Drug
Intervention description(s): Somatostatin may be used to suppress endogenous insulin secretion
Intervention MeSH terms: Somatostatin
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Endocrinology clinic, community
      
Keywords: Type 1 diabetes; Hypoglycemia unawareness; Islet transplant