Postprandial effects of a low vs. a high glycemic index food product on metabolic risk markers in lean and obese men

Dietary carbohydrates (CHO) with different chemical compositions (e.g. sugars,
oligosaccharides, starches and nonstarch polysaccharides) and physical
structures are digested and absorbed at different rates in the human small
intestine, and therefore give rise to different blood glucose and insulin
responses. These differences formed the basis of the glycemic index (GI), which
was introduced by Jenkins et al. in the early 1980s. It is a measure of the
change of blood glucose in healthy lean subjects following ingestion of a fixed
quantity of carbohydrates from a food. Some foods result in a marked rise
followed by a more or less rapid fall in blood glucose (high-GI foods), whereas
others produce a smaller peak along with a more gradual decline in plasma
glucose (low-GI foods). The rate of glucose entry into blood and the duration
of the elevated blood glucose are known to induce many hormonal and metabolic
changes that may affect health and disease parameters. Many experts now
consider the manipulation of the dietary GI as a useful tool for the treatment
and prevention of chronic diseases typical of industrialized countries. As
suggested by large prospective observational studies, including 2 meta-analyses
, a higher 120 min post load blood glucose concentrations independently
predicts cardiovascular morbidity and mortality in individuals without
diabetes. Moreover, randomized dietary intervention trials showed that low-GI
diets may be associated with improvements in cardiovascular disease risk
factors, including reduced LDL cholesterol and triacylglycerols (TG), and
improved insulin sensitivity. Results between studies are however inconsistent.
In our previous intervention study (results not yet published: MEC: 05-139)
with overweight subjects the longer-term effects of food products, different in
GI, were investigated on fasting glucose and lipid metabolism, and on
inflammatory markers. No differential effects of the diets were found on these
parameters after one day or after 11 weeks. In general, results of studies on
the effects of carbohydrate consumption on inflammatory parameters are
controversial. Pereira et al., for example, found that a diet with a
low-glycemic load (GL, which is derived from the GI) lowered CRP levels
compared to a low-fat diet. Sorensen et al., however, found no effects on CRP
concentrations after 10 weeks consumption of an artificial sweetener as
compared to sucrose. In these studies, the diets not only differed in GI, but
also in fiber, protein, and fat content. Therefore, effects of GI on
inflammatory parameters remain controversial. It is, however, also possible
that in our intervention study the difference in GI between the diets may have
been too small to detect any difference in inflammatory markers. Moreover, it
may be more important to look at the postprandial effects of diets with
different GIs, because subjects spent most of the day in the postprandial
state. Motton et al., however, found in healthy overweight women no increase in
monocyte activation of monocytes after consumption of a high GL meal as
compared to a low GL meal. Again, the GL was not the only difference between
the experimental diets, which may have confounded comparisons. However, it is
also possible that the GI or GL of a meal or a diet will influence the
inflammatory response in persons who are more sensitive to the carbohydrate
content of the diet.
Thus, there is a need to carry out a more controlled postprandial study in
obese subjects. Based on these considerations, we want to investigate the
postprandial effects of a low-GI vs. high-GI food on inflammatory markers in
obese subjects. As already mentioned, the GI is calculated in lean subjects,
but low-GI food products are the most useful for overweight and obese subjects
because they have an increased risk of developing type 2 diabetes or CVD.
Therefore, a second objective is to compare the effects of the GI of a food
product on inflammatory markers in lean and obese subjects.

The major research question is:
Does a low-GI food product improve in healthy and obese men postprandial plasma
concentrations of inflammatory markers as compared to a high-GI product?

Major null hypothesis, H0:
In healthy as well as obese men, a low-GI food product does not lower
postprandial plasma IL-6 concentrations when compared with a high-GI food
product.

Major alternative hypothesis, Ha:
In healthy as well as obese men, a low-GI food does lower postprandial plasma
IL-6 concentrations when compared with a high-GI food.

Minor null hypothesis, H0:
The effect of a low-GI food product vs. a high-GI food product on postprandial
plasma IL-6 concentrations is not different between healthy lean and obese men.

Minor null hypothesis, Ha:
The effect of a low-GI food product vs. a high-GI food product on postprandial
plasma IL-6 concentrations are more pronounced in healthy obese men as compared
to those in healthy lean men.

This study consists of a randomized, crossover study. 15 lean and 15 obese men
(aged 18-65y) will be included. Before the start of the study, subjects will be
randomly assigned to one of the three products; both groups will receive a
low-GI and a high-GI cookie, and on 2 other test days a glucose solution to
enable us to calculate the GI of the cakes. Between each intervention day, a
wash-out period of minimal 3 days is included. There are no indications that
carry-over effects will occur after a 3-day wash-out period.
The GI of the food products, cookies with different glucose / patent flour
ratios (table 2) will be determined, based on standard and accepted protocols.
For this, we have based us on the formal protocol recommended by the Food and
Agriculture Organization (1998). According to this protocol, healthy people
will receive a portion of the cookie containing 50 grams of digestible
(available) carbohydrate. After a fasting blood sample, the cookies will be
consumed and for the next two hours plasma glucose levels will be measured at
defined time points. For each person, the area under the curve (AUC) of plasma
glucose levels, corrected for fasting glucose concentration and ignoring
concentrations below fasting concentrations, will be calculated for each
cookie. On two other occasions, the same people will consume a reference
glucose solution (providing the same amount of carbohydrate) and their two-hour
blood glucose responses will also be measured. A GI value for the test food is
then calculated for each person by dividing their glucose AUC for the test food
by their glucose AUC for the reference food (mean of two tests). The final GI
value for the test food is the average GI value for all participants. The
evening before a test, each subject should consume a meal of his own choice and
repeat that same meal before each subsequent test. Subjects will be asked to
arrive at the same time for each session. At each test, a standard amount of
250 ml water will be given. The glucose solution is composed of 50 g glucose
diluted in 250 ml water.
In both the lean and obese groups multiple measurements will also be made to
follow the time course of metabolic risk markers in plasma after eating the
low-GI or a high-GI food product. Blood samples will be taken at time 0, 15,
30, 45, 60, 90, 120, 180 and 240 minutes after breakfast. Body weight will be
measured each day in the morning. Results will be used to relate GI with
markers for low-grade systemic inflammation, endothelial function, as well as
with parameters related to glucose and lipid metabolism.
The subjects will record in diaries any signs of illness, medication used, and
any deviations from the protocol. In addition, subjects are urged not to change
their level of physical exercise or use of alcohol during the study. The
subjects are instructed to keep a stable body weight; therefore at each visit
we will record body weight.

Table 1: Experimental design
Product 1* Product 2** Product
3 Product 3
Group lean (N=15) Low-GI cookie High-GI cookie Glucose
solution Glucose solution
Group obese (N=15) Low-GI cookie High-GI cookie Glucose solution Glucose
solution
** 30 gram of glucose / 10 gram of patent flour
* 0 gram of glucose / 40 gram of patent flour
Products will be provided in random order.

2 mornings consumption of low- or high-GI cookie
2 mornings consumption of glucose solution

Before the start of the study subjects will be screened to access eligibility
(visit duration 30 min). At the screening visit body weight, body length, and
waist and hip circumference will be measured. Subsequent, each subject will be
randomly allocated to one of the three products (low-GI cake, high-GI cookie or
twice a reference glucose solution). In the test period, the subjects will
visit the department 4 times. During these visits an indwelling cannula will be
inserted in an antecubital vein and when the subjects consume the cookies 9
blood samples (172 mL in total) will be taken during 4 hours. When subjects
consume the reference glucose solution 7 blood samples (28 mL in total) will be
taken during 2 hours. Total time investment for the subjects will be ± 14
hours. During this period, subjects will be at the university. Blood sampling
might cause bruises or haematoma.