Alcohol Exposure in Pre- and Early Post-Natal Stages May Cause Insulin Resistance

January 2004 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. Grgoire 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).


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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.


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.


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.

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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).