Prenatal Exposure to Alcohol Linked to Diabetes

Journal of Applied Physiology
18 Dec 2003

Alcohol Exposure During Prenatal Or Early Postnatal Period May Result In
Insulin Resistance, Glucose Intolerance Later In Life

(Bethesda, MD, USA) – Perinatal factors (those occurring about five months
before birth and one month after) have been implicated in the development of
Type 2 diabetes and other disorders.

Although the association of adverse events during pregnancy and glucose
intolerance has been well documented, little is known about the effects of certain
events that occur only during the postnatal period.

It is important to understand such effects involving lactation because
alcohol consumption among nursing women is common and there is a popular belief that
alcohol (i.e., maternal ethanol (EtOH)) promotes lactation.

Ingested EtOH is secreted in the milk and therefore has the potential for
exposing the developing offspring to toxic effects of EtOH. A new study finds
that alcohol exposure during early development -- though not necessarily during
pregnancy -- may program the offspring for insulin resistance and glucose
intolerance later in life.

A New Study

The authors of the study, “Whole Body Insulin Resistance in Rat Offspring of
Mothers Consuming Alcohol During Pregnancy or Lactation: Comparing Prenatal
and Postnatal Exposure,” are Li Chen and B. L. Grégoire Nyomba of the Department
of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, CN. Their
findings appear in the Journal of Applied Physiology, “Articles in Press”
section. The Journal is one of 14 scientific journals published each month by the
American Physiological Society (APS).

Methodology

The research team followed the protocol outlined below:

Animals: Timed-pregnant Sprague-Dawley rats were used (n=3-4/group) and
randomly divided into three weight-matched groups. Throughout pregnancy, one group
was given 2g/kg EtOH (36%) twice daily and the other groups were given the
same volume of water. Body weight and food intake were recorded daily.

From day 1 postpartum until weaning, one of the two groups that were not
given EtOH during gestation was given EtOH, while the other groups were given
water. Average litter size was 14 for each of the three groups.

Male offspring were culled to 4-5 per lactating dam and kept with their
mothers until weaning on day 21. Weaned offspring were housed and fed, and body
weight and food measurements were tracked.

Intravenous Glucose Tolerance Test: At 16 weeks of age, offspring from each
group underwent a frequently sampled intravenous glucose tolerance test
(IVGTT). The rats were later killed and incremental areas under the glucose (AUG) and
insulin (AUI) curves were calculated.

Acute insulin response to glucose (AIR) was calculated as the area under the
AUI for the first 8 min after the glucose challenge. A glucose tolerance index
(KG), representing the net glucose elimination rate in response to both
endogenous and exogenous insulin, was calculated.

Insulin sensitivity index (SI) was determined by modeling. The products of SI
with AIR were used as the disposition index (DI) to represent insulin effect.

Tissue Triglycerides: Tissue triglycerides were extracted and, later,
triglycerides were determined spectrophotometrically.

Other Assays: Plasma glucose was measured. Plasma insulin was measured with a
sensitive rat radioimmunoassay kit. Plasma free fatty acids (FFA) were
determined.

Statistics: Differences between groups were evaluated by ANOVA with Dunnett’s
multiple comparison test. Insulin values were log-transformed before analysis
and values expressed as the mean ± SEM. P<0.05 were considered significant.

Results

The researchers noted the following:

· Animal weight and food intake: All male offspring in the control group and
in the group exposed to EtOH during lactation had a birth weight greater than
6.0 g. Among male offspring exposed to EtOH during pregnancy, 12 had a birth
weight smaller than 6.0g, whereas 9 were within the control range.

The offspring exposed to EtOH during pregnancy were further separated into
two subgroups: small and normal weight at birth. In the prenatal EtOH group,
offspring that were small at birth had a catch up growth after 4 weeks of age, at
which time their growth rate became indistinguishable from controls.

This was also the time their food intake, which was slightly reduced during
the first 2 weeks post-weaning, increased to controls levels.

Surprisingly, however, offspring in the prenatal EtOH group that had a normal
birth weight had a slower growth rate by 11 weeks of age, despite normal food
intake. Offspring exposed to EtOH during lactation had a growth curve that
was comparable to controls.

· Glucose Tolerance and Insulin Sensitivity: The glucose curves were similar
among the three EtOH groups, but showed higher glycemiae compared with control
rats, especially during the last 70 min. The AUG curves were also similar
among the EtOH groups and were significantly greater in all three groups compared
with controls.

Both groups of offspring that were exposed to EtOH before birth had elevated
AIR, with the greater value in the lighter group compared with controls. AIR
in offspring exposed to EtOH during lactation was similar to controls. KG, SI,
and DI were significantly decreased in the three EtOH groups compared with
controls. SG was not different between groups. Pooled data showed a hyperbolic
relationship between AIR and SI.

· FFA and Triglycerides: Because hypertriglyceridemia and accumulation of
triglycerides in nonadipose tissues have been associated with insulin resistance,
the researchers measured plasma FFA and triglyceride as well as muscle and
liver triglycerides.

Plasma FFA levels were similar between EtOH groups and controls. However,
plasma, muscle, and liver triglyceride levels were about twofold higher in EtOH
rats that were born small compared with controls. Surprisingly, plasma and
tissue triglyceride levels in the other two EtOH groups were comparable to
controls.

Conclusions

This study demonstrates that exposure to EtOH during early development,
albeit not necessarily during pregnancy, may program the offspring to abnormal
glucose homeostasis later in life.

Further, EtOH exposure during the prenatal or early postnatal period resulted
in insulin resistance and glucose intolerance later in life. The underlying
mechanisms are still unknown, however, and require further investigation.

Source: Journal of Applied Physiology, “Articles in Press” section. The
Journal is one of 14 scientific journals published each month by the American
Physiological Society (APS).

The American Physiological Society (APS) was founded in 1887 to foster basic
and applied science, much of it relating to human health. The Bethesda,
MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14
peer-reviewed journals every year.

Editor’s Note: A copy of the research article is available in pdf format to
the press. Members of the press are invited to obtain a pdf copy of the study
and to interview members of the research team. To do so, please contact Donna
Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell) or djkrupa1@aol.com.