Performance of the Eversense vs the Free Style Libre Flash
Monitor in (before, during and after) strenuous and extreme exercise conditions in subjects with diabetes

In subjects with diabetes, adequate to good metabolic control is necessary for
a variety of reasons. In active subjects who perform exercising and sports
activities, adequate glucose control, including prevention of hypo- and
hyperglycemias, would allow good performance. This will even more so the case
when the sports activity is going to the strenuous and extreme.
One variation on earlier continue glucose monitoring (CGM) is FreeStyle Libre
Flash Monitor (FLFM) an improved easiness of use and practical applicability.
Relying on a CGM device implicates the assumption, that the device will be
accurate and reliable. Another device registering glucose continuously, is
entering the market: Eversense (Senseonics Inc.) (ECGM).
For assessment of the accuracy and reliability of both the FLFM and the ECGM
under strenuous to extreme sports conditions, it is proposed to perform a
head-to-head comparison of these devices before , during and after the Bas van
de Goor Foundation *we bike to change diabetes* challenge in September 2018,
when a combined team of subjects with diabetes from the Netherlands and Spain
will mountainbike in the Sierra Nevada for six days, with a total minimum
distance of 263 km and a variable amount of altitude meters (minimal 4753 up to
11000 meters)
(https://bvdgf.org/evenementen/evenement/27041/webike2changediabetes-2018/).

As far as we are aware, the effect of strenuous or extreme exercise on the
performance and accuracy of both the ECGM and the FLFM has not been studied
extensively outside a clinical setting.

Hypothesis
ECGM will perform better during strenuous to extreme exercise than FLFM


Background
In the past 15 years, continuous glucose monitoring (CGM) systems have become
available. These CGM systems measure interstitial fluid glucose levels at
rather closely spaced intervals to provide semi-continuous information on
glucose levels, allowing identification and signaling of glucose level
fluctuations to a degree that cannot be obtained with intermittent capillary
blood glucose measurements. While improved glycemic control has been
demonstrated with the use of CGM systems, CGM accuracy also remains a
challenge; most of the available systems need calibrating at least twice daily
to allow a sufficiently reliable correlation between interstitial and capillary
glucose results. Nevertheless, with the advances in the development of highly
accurate and easy to use CGM systems, the ultimate use of an *artificial
pancreas* moves closer to become a reality.
Recently, two different variety of a continuous glucose measurement for
interstitial glucose fluid monitoring has been introduced in Europe the
FreeStyle Libre (Abbott) and the Eversense (Senseonics). FreeStyle Libre is
compact, lightweight, has a two-week period of use, and according to the
producer does not require calibration by the user (factory-calibrated): the
FLFM. Scanning of the sensor by the reader collects the glucose and trend at
the moment of scanning plus up to 8 hours of prior readings every 15 minutes.
The reader used for FLFM also supports glucose and ketone capillary blood
measurements using capillary BG and ketone test strips (Free Style Precision
capillary glucose test glucose/ketone strips.).

The Eversense CGM System includes an implantable sensor that lasts up to 90/180
days, a removable smart transmitter, and a mobile app. The system needs
calibration twice a day.
The Eversense CGM system measure glucose from interstitial fluid below the skin
surface.
The sensor wirelessly sends glucose data to the smart transmitter worn on the
upper arm over the sensor insertion site. The smart transmitter calculates the
current glucose values along with the direction it*s headed, how fast, and
whether glucose values are expected to exceed pre-set low and high targets.
Data and alerts are simultaneously sent to the smartphone app that provides
real-time tracking, intuitive displays to help identify patterns, and
information to help stay in range.

Independent accuracy assessments of the FLFM are scarce; findings of a study
recently performed at our department indicate that the FLFM system in the arm
can be used as a workable adjunct in the management of diabetes. However,
certain matters definitely need attention while using the CGMs in daily.
Effects of deviations can partly be overcome by optimizing the available user
instructions.

To assess accuracy of ECGM vs FLFM in 25 subjects with diabetes before, during
a 6 day mountainbike tour and after the tour in the Sierra Nevada

To assess the (differences in ) time in hypo-, normo- ,and hyperglycemia
(expressed in minutes per day and episodes per day), using cut-off point as
defined by Bolinder et al (ref 8). MAD and MARD in glucose concentrations,
using the same incremental glucose concentration steps as in the validation
study. Parkes Error grids (ISO15197:2013)

Prospective, observational study, comparing different methods to assess
reliability and accuracy of glucose measurements during strenuous to severe
exercise. Specifically: comparison of two devices with capillary measurements.

Data read-out before and during and after the challenge, concentrating on
available information from ECGM and FLFM, as well as the capillary blood
glucose (automatic stored in FLFM reader( measurements (to be performed as
standard 7 times daily, and on indication (hypoglycemic symptoms; hypoglycemia
shown on one or both of the devices, also when no hypoglycemia symptoms are
present).

Insertion and removal of the ECGM:
Insertion and removal of the sensor will be done by certified doctors. A doctor
is certified by Senseonics after three insertions.
Insertion and instruction of using the sensor will be done within 2 months
prior to the Sierra Nevada Challenge.

For Spain:
Because the participants are divided over Spain, we will look at 4 suitable
hospital locations where the insertion can take place performed by certified
doctors for this action (Pamplona, Madrid, Sevilla/Granada and Oviedo).
For The Netherlands:
Insertion will take place at the Isala Hospital in Zwolle by certified.

Insertion of the FLFL:
Insertion of the FLFL will be done first day at the Sierra Nevada

In principle, CGM is a common use in subjects with diabetes performing
strenuous to extreme sports / exercise. The extra burden is that one sensor
will be placed via a small incision and wearing not one but two devices. No
extra risks involved