The effect of egg protein hydrolysate on arterial stiffness in overweight or moderately obese subjects with impaired glucose tolerance / diabetes type 2

The incidence of type 2 diabetes mellitus (T2DM) is rapidly growing, Patients
with T2DM are at increased rik of developing long term micro- and macrovascular
complications ; occuring in 40-56% of the T2DM patients in the Netherlands.
T2DM accounts for almost one in ten death around the world; up to 80% of these
deaths are related to cardiovascular disease. Subjects with impaired fasting
glucose (IFG) or impaired glucose tolerance (IGT) show slightly elevated
fasting glucose levels, or increased blood glucose levels after an oral glucose
load, respectively, but do not fulfill the criteria of diabetes. Approximately
30% (i.e. 900,000 persons) of the Dutch population over 60 years is thought to
have an impaired glucose tolerance, currently more commonly referred to as
pre-diabetes. These subjects are generally still considered heatlhy, but do
have a markedly increased risk of later development of T2DM.
The development of T2DM can be prevented or delayed by nonpharmacological
interventions, in the form of lifestyle modifications such as losing weight,
increasing physical activity and a healthy diet. These lifestyle modifications
are recommended as step 1 in the treatment of T2DM and IGT in both national and
international guidelines. To support these lifestyle changes and proactively
reduce the risk of development of T2DM, attempts are also made to modify
commonly available foods by removal (of components) or enrichemnt. These
so-called functional foods are currently very popular among the population.
Recently an ingredient isolated as hydrolysate from egg protein has been
experimentally shown to improve the endothelial function. Furthermore, acute
ingestion resulted in in vivo studies in mild yet significant inhibition of
plasma ACE activity and reduction of blood pressure in spontaneously
hypertensive rats. Therefore, this protein hydrolysate is a typical example of
an interesting ingredient for the treatment of cardiovascular dysfunction
associated with the metabolic syndrome and type 2 diabetes.

To assess the short-term (2 hours, and 2 days) effects of the egg protein
hydrolysate on arterial stiffness in volunteers, aged 18-70 years with
overweight and impaired glucose tolerance (defined as blood glucose >7.0 mmol/l
and <11.0 mmol/L, two hours after ingesting 75 gram glucose in 250 ml water) or
T2DM.

A , randomized, double-blind, cross-over design with assessment of effects on
the vascular function at baseline, 2 hours and 2 days after oral administration
of 5 grams protein hydrolysate or placebo capsules, respectively.

The egg protein hydrolysate or placebo (amylum as inert filling material) will
be given to the participants in capsules. The subjects will take the
hydrolysate or placebo capsules (5 gr/day) on study days 1, 2 and 3 during two
periodes seperated by a washout period of minimally two weeks.

Before the start of the study, subjects will be screened to determine
eligibility; diabetic stability will be determined during an interview and
impaired glucose tolerance (glucose > 7.0 mmol/l) will be assessed by an oral
glucose tolerance test (only for subjects who are not already diagnosed with
T2DM). Upon arrival at the study center in the fasting state, subjects will
take a glucose drink and blood will be samples once after two hours to evaluate
2h glucose concentrations. In addition, body weight, height and blood pressure
will be measured. The visit lasts approximately 2,5 hours. The study itself
includes 4 study days; duration of the first and third day of both periods will
be approximately 2,5 hours in the morning. On both days, subjects may not have
any food or drinks other than water and their usual medication up till the end
of the study session.
In total, the subjects will have nine blood samples taken, i.e. one during the
screening process (1 x 3,5 ml) and eight during the study itself (8 x 15 ml)
(day 1: fasting, 1h and 2h, and day 3: fasting during each research period). to
determine lipid profile, glucose, insulin, incretins, liver and kidney function
parameters, HbA1c, and markers of relecting endothelial function and
inflammation). Thus the total amount of blood sampled throughout the study is
123,5 ml. On rare occasions, blood sampling might cause bruises or haematoma.
Total investment for the subjects (screening plus study) will be approximately
12 hours and 30 minutes.