Highlights From the Society for Gynecologic Investigation 51st Annual Meeting

John F. Randolph, Jr, MD


April 18, 2003

In This Article

Fetal Origins of Adult Diseases -- Insulin Resistance

Peter Gluckman, Director of the Liggins Institute at the University of Auckland in New Zealand, gave the SGI International Lecture on the potential mechanisms of the fetal origins of adult diseases. He reviewed the relatively recent recognition of the relationship between low birth weight and later rates of coronary heart disease and type 2 diabetes mellitus. This finding has led to the concept that the fetus interacts with its environment, specifically with regard to nutritional availability, and is "programmed" for lifelong metabolic and behavioral adaptation. Individuals who are nutritionally restricted in utero and are small during development or at birth tend to hold on to calories, gain more weight, and be less active than well-nourished peers. He presented evidence demonstrating that growth-restricted babies have decreased insulin sensitivity and that even infants with early growth restriction from which they recover and achieve a normal birth weight have insulin resistance and a tendency to premature labor.

These data, and animal models, have prompted the "couch potato syndrome" concept that somewhat pessimistically argues for a fetally programmed tendency to unrestricted eating and decreased activity that may have little potential for behavioral modification. This tendency has been proposed as a major predisposing factor for coronary heart disease, diabetes mellitus, dyslipidemias, syndrome X, osteoporosis, polycystic ovary syndrome, and such diverse disorders as psychoses, mood disorders, psychosexual problems, obstructive pulmonary diseases, and immune disorders.

Dr. Gluckman offered a genetic explanation for this phenomenon whereby early developmental genes are imprinted by nutritional status, leading to variations in tissue differentiation. Nutritional restriction may lead to a "thrifty phenotype" that seeks and retains calories throughout life. Conversely, a "thrifty genotype" may be genetically predisposed to the same tendency and require less nutritional restriction to become a calorie saver. Either way, the genotype interacts with its environment very early in a way that may be the final common pathway to adult diseases such as syndrome X. He summarized with the image of a "human camel," programmed very early in gestation to hoard calories in response to nutritional restriction and condemned to a lifelong struggle with a surplus of stored energy in a society where food supplies are plentiful.

Comment: Although the concept that early fetal programming of behavior may make adult behavior modification nearly impossible is quite discouraging, if true, it also holds the possibility that environmental modification early in gestation may offer a public health strategy that could have far-reaching implications if applied on a population-wide basis. Research on the effects, and the potential manipulation of those effects, of maternal nutrition and behavior on the fetus has not received much attention until now, and seems to be an area whose time has come.


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