Effect of moderate alcohol consumption on postprandial insulin secretion, appetite regulation, glucose homeostasis and insulin resistance.

A body of epidemiologic studies shows that moderate alcohol
consumption is associated with a protective effect against type 2 diabetes. The
importance of both insulin sensitivity and insulin secretion in the
pathogenesis of glucose intolerance and diabetes type 2 is widely recognized.
Clinical studies show improved insulin sensitivity after a period of alcohol
consumption compared to abstention. However, postprandial insulin secretion and
beta-cell function after a period of moderate alcohol consumption have scarcely
been addressed in published literature.
When consumed as an aperitif or with a meal, alcohol is generally
expected to stimulate appetite and food intake and thus might be a risk factor
for over consumption and obesity. However the physiological mechanisms for this
observed effect are not well understood. Furthermore, previous studies lacked a
link between physiological parameters and subjective parameters of satiety.

Previous studies have shown that moderate alcohol consumption improves
insulin sensitivity in post menopausal women and other markers of glucose
homeostasis, such as HbA1c in young men. Whether these markers also improve in
pre menopausal women and whether other markers related to glucose homeostasis
also improve after moderate alcohol consumption is unknown.
Adiponectin is an adipose tissue-derived protein. Low levels are
associated with obesity, insulin resistance and type 2 diabetes. Several
clinical studies show an increase in adiponectin concentrations after a period
of moderate alcohol consumption. However, there is little knowledge about the
kinetics of alcohol-induced increases of adiponectin.
It has been shown that diet intervention studies are powerful enough to
trigger significant differences in gene expression of adipose tissue. These
intervention studies have the power to reveal important signalling pathways
involved in glucose and fatty acid metabolism. There is little knowledge on
whether moderate alcohol consumption changes gene expression of these pathways.

Objective:
Primary objectives are to study the effects of moderate alcohol consumption on
- Postprandial insulin secretion and pancreatic beta-cell function
- Physiological and subjective parameters related to satiety and appetite
Secondary objectives are to study the effects of moderate alcohol consumption on
- Miscellaneous markers of glucose homeostasis and insulin sensitivity
- Kinetics of alcohol-induced increase of adiponectin
A tertiary objective is to study the effects of moderate alcohol consumption on
- Gene expression in subcutaneous adipose tissue
in normal-weight pre menopausal women with normal fasting plasma glucose.

Study design: Randomized, partially controlled, open label, cross-over study
with a one week wash-out preceding each treatment period

Participants will drink daily a test substance for three weeks (2 cans of
Amstel beer per day; 66 cL ~ 26 gram alcohol) followed by a reference substance
(2 cans of Amstel alcohol-free beer per day; 66 cL < 0.5 gram of alcohol) for
three weeks or vice versa. Both treatments are preceded by a one-week wash-out
period in which no alcohol is consumed.

Subjects need to visit the study site in total 10 times during the study period
of 57 days (see figure § 11.4).
The ten visits in study will consist of eight visits for collecting fasted
blood samples, body weight measurement and morning urine collection and two
visits for a lunch after which several blood samples, appetite and PPW
questionnaires on VAS will be taken over a period of time and a fat biopsy from
the buttocks. The total amount of blood, urine and fat tissue collected during
the whole study will be ca. 522 mL, 50 mL and 600 mg respectively. At each
visit, subjects need to fill in a short well-being questionnaire.

According to the knowledge of the author, no studies are published on the
effect of moderate alcohol consumption on insulin secretion (or insulin
sensitivity) and beta-cell function in pre menopausal women.
The study will be performed in normal-weight pre menopausal women with normal
fasting glucose, because young men and women and lean women with a normal
fasting glucose show tendencies of increased insulin secretion and improved
glucose sensitivity (parameter of beta-cell function) during a meal after
moderate alcohol consumption compared to abstention. This study will only be
performed in lean women since lean and obese women do not use energy from
alcohol with equal efficiency.

To minimize any differences in appetite regulation due to fluctuations in
steroid hormones related to the menstrual period and to have a more homogenous
group, only women who use oral contraceptives will be included in the study.
The two test days on which appetite regulation will be measured are exactly
four weeks apart for each person. Therefore, it does not matter in which day of
the menstrual cycle the subject is since the treatment is approximately on the
same day in the menstrual cycle. Furthermore, plasma concentrations of sex
steroid hormones are quite stable during the whole menstrual cycle when using
oral contraceptives.
The lunch at TNO will have a fixed size since a laboratory environment may
promote over consumption.