Sensing With Insulin Pump Therapy to Control HbA1c

Improving glycemic control in people with diabetes, has been shown to decrease
risks of micro-vascular, neurological, and renal complications associated with
the condition[1]. The landmark DCCT trial [1] also clearly established that
achieving an HbA1c of 7.0% or less through an intensive insulin therapy (IIT)
can reduce or delay the incidence and onset of diabetic complications.

In current clinical practice IIT with multiple daily injections (MDI) or
continuous subcutaneous insulin infusion (CSII) is well established to lower
and maintain average glucose levels. Nevertheless, patients trying to reduce
their HbA1c often achieve this at the expense of increased risk of
hypoglycemia.

Reaching target HbA1c levels depends upon monitoring blood glucose (BG) levels
and titrating therapy to reduce glycemic excursions. Reducing glycaemic
excursions minimizes the risk of acute complications of hypoglycaemia and
diabetic ketoacidosis. Strict glycemic control is more difficult to achieve
with MDI, due to variability in absorption[4] and timing of insulin injections.
This reason often precipitates a switch to CSII. Several studies have shown
superiority of CSII over MDI regarding clinical outcomes[2-11] and quality of
life [5-13] .

The majority of patients assess their BG through self monitoring blood glucose
(SMBG) using fingerstick measurements, to assess and adjust their therapy.
Nevertheless, many patients perform SMBG tests infrequently due to
inconvenience, pain, or therapy burden. Using only SMBG as reference point to
establish glycemia profiles results in a certain amount of missed hyper- and
hypoglycemic events every day [14-15]. Moreover, the DCCT trial[1] showed that
subjects in the IIT arm experienced a 3.3 fold higher incidence of severe
hypoglycemia than the control group despite performing SMBG four or more times
daily.

It is possible to avoid missing hyper- and hypoglycemic excursions with the
development of new devices which continuously measure and display continuous
glucose values. Several studies using these devices have demonstrated that
availability of continuous glucose values helps patients reduce hyper- and
hypoglycemic excursions, and improve HbA1c values [16-21]. In 2006, Deiss et
al[22] published the first randomized controlled clinical trial evaluating
whether Type 1 patients using MDI or CSII, in poor glycemic control could
improve HbA1c using a continuous glucose monitor, the Guardian REAL-Time®. This
trial demonstrated a significant reduction in HbA1c over 3 months.

To determine whether patients with Type 1 diabetes mellitus in sub-optimal
glycemic control can achieve better glycemic control as evidenced by a drop in
HbA1c using the Medtronic MiniMed Paradigm® REAL-Time Pump and the continuous
Glucose Monitoring System versus the Medtronic MiniMed Paradigm® REAL-Time Pump
alone with Self Monitoring Blood Glucose (SMBG).

This study is a randomized, two-arm, controlled, cross-over, multi-center trial
in adult and pediatric subjects in Europe. There is a wash out period between
the two treatment phases.

The study is a post-market release trial, as all study devices and related
software (see section 5.3) are CE marked.

There are possible risks and side effects connected to the device and followed
procedures. Possible additional risks include the following (although others
are possible):

*Skin irritation, bruising, discomfort, redness, bump, bleeding, irritation,
pain, rash, infection, appearance of a small *freckle-like* dot where the
sensor needle was inserted, local infection at sensor site and allergy to
sensor components or dressing.

If irritation of the insertion site is noted, then the sensor will be removed.
It is recommended to wear the glucose sensor for 3 days. If it is worn for
longer periods it may cause such problems. To ensure correct placement of the
sensor and to minimize discomfort upon insertion, an insertion device
(Sen-Serter) will be used to insert the sensor (Sen-Serter will be provided to
you at the beginning of the study treatment).

*Alarms may alert you that you are too high or too low, and on checking your
blood glucose with a fingerstick, you may find that the value is acceptable.
Nevertheless it can happen that the alarm alerts you unnecessarily.
This should be discussed with your physician so that the alarms can be adjusted.

*Inaccurate glucose values or inappropriate alarms provided by the device could
result in inappropriate administration of insulin or ingestion of
carbohydrates. Such inappropriate treatment decisions could result in
exacerbation of the symptoms associated with hypoglycemia and hyperglycemia.

Such risks can be minimized if you always follow the instruction to confirm any
hypoglycemia, hyperglycemia alarms or symptoms using the glucose meter prior to
taking any action based on the alarm or displayed glucose values.

In case of risks outweighing the benefits for your well-being, your physician
or Medtronic can decide to terminate your participation in the clinical study.