The effect of hesperidin administration on glucose / insulin metabolism

From epidemiological data it is observed the prevalence of overweight and the
prevalence of illnesses such as metabolic syndrome and cardiovascular diseases
have greatly increased over past decades. The metabolic syndrome represents a
combination of cardio-metabolic risk determinants including obesity (central
adiposity), insulin resistance, glucose intolerance, dyslipidemia and
hypertension. This syndrome is defined as a multifactorial disorder involving
hypertension (HTN), hyperglycemia and hyperuricaemia. Overweight is considered
to be an important factor in the etiology of the metabolic syndrome as it
contributes to insulin resistance, hyperglycemia, high serum cholesterol, low
High-density Lipoprotein (HDL) cholesterol, HTN, chronic low-grade inflammation
and it is associated with higher cardiovascular disease (CVD) risk. The
interest in this syndrome lies on the increased risk of developing DM2 and
cardio- and cerebrovascular diseases. Furthermore, under energy-rich
conditions, the inflammatory potential of metabolically important tissues can
be reactivated; the adipose tissue of obese individuals has been shown to
produce higher levels of pro-inflammatory factors. High-fat diet-induced
obesity is associated with alterations in microbial composition and mucosal
structure/functions (ref); this can result in a vulnerable microbial barrier
and increased permeability of the intestine. This decreased barrier function
may lead to movement of intestinal bacteria and/or lipopolysaccharides (LPS)
into the circulation with chronic systemic low-grade inflammation as a result
and this chronic inflammation plays an important role in the development of
many chronic metabolic diseases.
This plethora of diseases is correlated with genetic predisposition and
unfavorable lifestyle, characterized by low physical activity combined with
overconsumption of food. Its common fundamental pathogenic component is
resistance to insulin.

To determine the effects of daily administration of hesperidin on
glucose/insulin metabolism and intestinal health as assessed by an oral glucose
tolerance test (OGTT), and investigation of lipid metabolism, blood pressure,
heart rate, gut barrier function and body composition in overweight subjects.

This is a randomized, double-blind, placebo-controlled study of parallel
design.

Participants will be randomly assigned to one of the intervention groups. One
group will receive one daily dose of 500 mg Cordiart*, while the other group
receives an identical looking placebo capsule for a period of 6 weeks. The
capsules will have to be ingested with a glass of water (200 ml) every morning
just before breakfast.

There are several burdens volunteers can experience during the study period.
Upon inclusion, study procedures will take maximum 9 hours for each of the
subjects. Subjects will visit the MUMC+ at five test days. Subjects will have
to take 500 mg Cordiart* or placebo supplements before breakfast daily for a
period of 12 weeks; the supplements are safe for human use. Participants are
not allowed to eat hesperidin rich foods during the complete studie period.
They also are not allowed to smoke. On days before test days study participants
will have to abstain from physical exercise and cannot use alcohol, and they
will have to come to the test days in fasted state. During the test days the
following measurements will be performed:
- OGTT measurement (test day 2 and 5). This will take approximately 3 hours
- Venapunctures (maximum 176 ml)
- Collect feces (3 times)
- Collect 24 hours urine (2 times)
- Fill out food diary (2 times, during 3 days)
- Blood pressure- and heart rate measurements