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Changing the trajectory
Both maternal obesity and gestational diabetes get at the heart of the Barker Hypothesis, albeit a twist, in that excessive maternal adiposity and associated insulin resistance results in high maternal blood glucose, transferring excessive nutrients to the fetus. This causes accumulation of fat in the fetus and programs the fetus for an increased and persistent risk of adiposity after birth, early-onset metabolic syndrome, and downstream cardiovascular disease in adulthood.
Dr. Dana Dabelea’s sibling study of almost 15 years ago demonstrated the long-term impact of the adverse intrauterine environment associated with maternal diabetes. Matched siblings who were born after their mothers had developed diabetes had almost double the rate of obesity as adolescents, compared with the siblings born before their mothers were diagnosed with diabetes. In childhood, these siblings ate at the same table and came from the same gene pools (with the same fathers), but they experienced dramatically different health outcomes (Diabetes 2000:49:2208-11).
This landmark study has been reproduced by other investigators who have compared children of mothers who had gestational diabetes and/or were overweight, with children whose mothers did not have gestational diabetes mellitus (GDM) or were of normal weight. Such studies have consistently shown that, faced with either or both maternal obesity and diabetes in utero, offspring were significantly more likely to become overweight children and adults with insulin resistance and other components of the metabolic syndrome.
Importantly, we have evidence from randomized trials that interventions to treat GDM can effectively reduce rates of newborn obesity. While differences in birthweight between treatment and no-treatment arms have been modest, reductions in neonatal body fat, as measured by skin-fold thickness, the ponderal index, and birthweight percentile, have been highly significant.
The offspring of mothers who were treated in these trials, the Australian Carbohydrate Intolerance Study in Pregnant Women (N. Engl. J. Med. 2005;352:2477-86), and a study by Dr. Mark B. Landon and his colleagues (N. Engl. J. Med. 2009;361:1339-48), had approximately half of the newborn adiposity than did offspring of mothers who were not treated. In the latter study, maternal dietary measures alone were successful in reducing neonatal adiposity in over 80% of infants.
While published follow-up data of the offspring in these cohorts have covered only 5-8 years (showing persistently less adiposity in the treated groups), the offspring in the Australian cohort are still being monitored. Based on the cohort and case-control studies summarized above, it seems fair to expect that the children of mothers who were treated for GDM will have significantly better health profiles into and through adulthood.