Validating the SteepRamp test for estimating the physical fitness and an AGE test to predict tendinopathy structure in diabetes.

Physical exercise has a prominent role in the treatment of type 2 diabetes
mellitus (DM2). This research project aims to improve exercise intervention
programs in DM2 by validating a novel easy applicable exercise test for
determining physical fitness (substudy A) and investigating if advanced
glycation endproducts (AGE) in the skin can predict tendon structure
abnormalities that predispose tendinopathy (substudy B).

Substudy A
To improve the result and adherence of an exercise intervention in DM2 a
individual tailored program is advised. Until now only a elaborative and
expensive spiro-ergometry is available to optimize a exercise program for the
individual patient. A short supra-maximal exercise test (SteepRamp-test, 25
Watt/10 sec) is used in post-chemotherapy patients and shows accurate
correlation with VO2max measured with spiro-ergometry. The SteepRamp test has
been proven safe in heart failure patients. Hence it can be suggested that the
SteepRamp-test is accurate and effective in estimating physical fitness in DM2
patients. The study targets to validate the SteepRamp exercise test for
estimating the VO2max in DM2 patients. The secondary objective is to correlate
these data to results from a sub-maximal exercise test (0,5-1-1,5 watt/kg.2
min), an activity monitor and an isokinetic quadriceps strength test. The
secondary goal aims to investigate the SteepRamp test as a measure to estimate
daily activity pattern and muscle strength and to determine reference values
for the DM2 population. To achieve the studies objective 135 DM2 patients (age
30-80 yr, BMI 27-40 kgm/2) will be included and undergo a spiro-ergometry, a
SteepRamp and the sub-maximal exercise test on separate days. Furthermore the
subjects will wear an activity monitor for 7 days and perform an isokinetic
strength test.

Substudy B
The prevalence of tendinomuscular overuse injuries is one of the main reasons
of premature termination of the exercise program in DM2. Chronic inactivity is
considered an important cause of musculotendinous deconditioning and subsequent
injuries. However, advanced glycation endproducts (AGE) of collagen in the skin
is a known manifestation of both type 1 and type 2 diabetes and can easily be
determined using a skin autofluorescence test. This research hypothesizes that
the glycation of collagen will also occur in the musculotendinous tissue
predisposing tendinopathy in both type 1 and type 2 diabetes patiënts. Skin
autofluorescence will be correlated with tendinopathy score based on a novel
ultrasonic tissue characterization (UTC) technique. To test the hypothesis a
group of 30 type 1 (aged 18-30 yr), and 30 type 2 (aged 35-60) diabetes
patients of substudy A, will be requested to undergo a skin autofluorescence
and UTC test. This group will be compared with a control group, matched for
age, body composition, activity level and gender. A foot pressure measurement
will be used to rule out biomechanical factors for tendinopathy of the Achilles
tendon. When the hypothesis can be confirmed, the results will guide new
research on tendomuscular overuse injuries and tailor-made prevention programs
for diabetes patients.

Substudy A
• Validating the supramaximal SteepRamp exercise test to determine physical
fitness in type 2 diabetes patients by correlating the result with a
conventional VO2max exercise test and determining the test-retest reliability.

Substudy B
• Comparing Achilles tendinosis incidence in diabetes patients with the
incidence in matched controls.

Substudy A
- Cross-sectional observational validation study, intra-subject controlled

Substudy B
- Observational case vs. matched control study

Substudy A
•Maximal exercise test on a bicycle using spiroergometry, ECG and non-invasive
blood pressure monitoring.
•Two times a 6 min. submaximal exercise test using the Åstrand protocol and a
short (approx. 1-2 min.) supramaximal SteepRamp-
test, performed with a 20-30 min intermediate pause. These tests will be
executed 7-10 days separated from the maximal exercise test.
• Registration of the daily physical activity during 7 days and carrying a
validated multi-sensor accelerometer (Actigraph*).
• Isokinetic strength measurement (Biodex*, 5 rep's, 60 gr/s) of the
quadriceps.
• Standardized Sit-to-Stand test (getting up form a chair in a standardized
way).
• Weight and length measurement.
• Fat percentage estimation based on skin fold measurements.
• Waist circumference measurement.
• Blood sample obtained once from venous punction and urine test.
Testing will be performed on 5 separate days with an intermediate period of
7-10 days in 2-3 weeks.

There is a small risk of cardiac ischemia/arritmia or a hypoglycemic event
during the exercise test. To reduce the risk of cardiac ischemia/arritmia all
exercise test will be executed in a hospital setting with ECG monitoring and
direct supervision of a physician. The risk of a hypoglycemic event is low
considering the exercise tests are short. If necessary carbohydrate solutions
or, in case of loss of consciousness, Glucagon (Glycagen®, 1 mg dissolved in 1
ml) are available.

Substudy B
• Weight and length measurement.
• Fat percentage estimation based on skin fold measurements.
• Waist circumference measurement.
• Forearm skin auto-fluorescence measurement using AGE-reader®
• UTC measurement of the Achilles tendon
• Foot pressure measurement
• Blood sample obtained once from venous punction and urine
test.
• Registration of the daily physical activity during 7 days
and carrying a validated multi-sensor accelerometer (Actigraph*).

No associated risks