Prenatal diet may affect insulin resistance for multiple generations

Insulin sensitivity is normalized in the third generation (F3) offspring of developmentally programmed insulin resistant
(F2) rats fed an energy-restricted diet
Original source: Nutrition and Metabolism 2008, 5:26
Authors: Daniel C Benyshek (corresponding author), Carol S Johnston, John F Martin and William D Ross
Publication date: 17 October 2008
DOI (digital document ID): 10.1186/1743-7075-5-26
Requires subscription? No
Publicly-available abstract: Yes

Synopsis:
A number of studies have shown that the way animals develop before birth can affect the birth weights, blood pressure, and glucose metabolisms of their children, grandchildren, and so on. Most research to date has only gone two generations beyond the original parents. This study takes observation to the third generation (great-grandchildren) and focuses on impairments to the animals' glucose metabolisms. A parent generation of female rats were fed protein-deficient diets while pregnant and nursing, and both they and three generations of their offspring were fed low-calorie diets, to see how this affected the insulin sensitivity of multiple generations of their offspring. A group of control rats was fed normal-calorie diets over the same number of generations.

The first generation of offspring (children) tended to be of low birth weight, while the second and third generations (grandchildren and great-grandchildren) were of normal birth weight. All generations were of lower than normal weight as adults, due to the caloric restriction. The first=generation offspring had normal insulin metabolism, While the second generation, as adults, had reduced insulin sensitivity and reduced insulin production -- a set of symptoms consistent with impaired glucose tolerance. The third generation did not show insulin resistance -- indeed, the males were even more insulin-sensitive than the control animals, whether they were fed calorie-restricted diets or allowed to eat at will.

Previous studies of this type showed insulin resistance in the first-generation offspring, which was not found in this particular study; however, the second-generation female offspring in this study were insulin-resistant.

The investigators are unsure why the third-generation offspring did not show impaired glucose tolerance or insulin resistance, even though both of those traits are considered to be adaptive traits that show up in "nutrient poor environments" (reduced protein, reduced calories). They suggest that one reason for this may be that the second-generation mother's insulin resistance left more energy in the bloodstream to be used by the fetus. On the other hand, the relative insulin sensitivity of previous-generation mothers (who had not been fed sufficient calories after weaning) made fewer nutrients available for the developing fetus, resulting in insulin resistance in the offspring.

The investigators suggest that more research is required to determine how pregnancy and nursing diets, and maternal insulin sensitivity, affects the insulin sensitivity of her offspring.

Reliability:
The authors are from accredited institutions, across a number of medical and social disciplines. The research was published in a peer-reviewed online journal. References are all from peer-reviewed journals. Therefore the experiment design is reliable. Since only four female rats from each child generation were bred, the study was small in size and therefore subject to skew. The authors did note that further research was warranted to find out why they got the results they did.

Practical Applications:
The normal birth weight and increased insulin sensitivity of child generations born to insulin-resistant mothers suggests a parallel mechanism for the large baby size common for human mothers with diabetes. While this study was conducted on rats, the rats are intended to be a shorter-lived and expendable model for human childbirth and development. A closer understanding of which maternal nutrients affect insulin resistance may lead to improved recommendations for pregnancy and nursing diets and supplements, and will ideally prevent insulin resistance in future generations of human adults.

This synopsis was based on the entire article.