The impact of dietary nitrate supplementation on exercise-induced cardiac troponin T release in type 2 diabetic patients: a pilot-study

Blood cardiac troponin T (cTnT) concentration is a widely used marker of acute
cardiac injury. Previous research has shown that several type 2 diabetic
patients show large increments in cTnT levels over the subsequent hours
following a single bout of moderate-intensity endurance-type exercise. This
phenomenon is likely attributed to cardiac ischemia-reperfusion injury caused
by reduced nitric oxide (NO) bioavailability. Recent evidence indicates that
ingestion of dietary nitrates dramatically increases the bioavailability of NO,
and as such, may be protective against cardiac ischemia-reperfusion injury.

To assess whether dietary nitrate supplementation blunts the
ischemia-reperfusion-induced rise in cTnT levels following exercise in type 2
diabetic patients.

The study is a double-blind, placebo-controlled, randomized cross-over trial.

After an initial screening, subjects will be randomly assigned to a test day
during which they receive a sodium nitrate (test supplement) or sodium chloride
(placebo) supplement. During each test day, subjects will ingest the dietary
nitrate or placebo supplement at 8:00 h and perform a single session of
moderate-intensity cycling exercise 2 hours later. Sixty minutes of
moderate-intensity endurance-type exercise will be performed at 50% Wmax. Blood
samples will be collected at baseline and over the 6 hour period following
exercise. After a wash-out period of at least 2 weeks, the intervention period
will be repeated with either the placebo or sodium nitrate supplement.

With the results of this study we hope to gain novel insight in the role of NO
bioavailability in ischemia-reperfusion induced cardiac injury in type 2
diabetic patients. Because candidate subjects participated in a recent study
(MEC 09-3-028; substudy E), cardiac function has been monitored by an ECG
within the last year. Subjects with severe cardiac abnormalities were excluded
for participation in that study. As such, only subjects without major cardiac
abnormalities are candidate to participate in the present study.

The exercise session will be performed at moderate-intensity (50% Wmax), and
has proven feasible in type 2 diabetic patients. In our previous studies (MEC
09-3-028) (20, 21) no adverse events occurred during or following exercise at
the same duration and intensity. In the present study, exercise will be
performed 1.5 h following breakfast and subjects receive lunch 1.5 h following
exercise. As such, the risk for exercise-induced hypoglycaemia is minimal.
However, in case subjects show hypoglycaemic symptoms, capillary glucose
concentrations will be measured with a finger prick and subjects receive
dextrose tablets when necessary.

The sodium nitrate and sodium chloride are human grade and do not pose any
health risk at the level administered. No known complications (besides a mild
headache) from a bolus ingestion of sodium nitrate have been reported.

At the insertion site of the intravenous catheter, a hematoma could occur.