Post-natal diet determines insulin resistance in fetally malnourished, low birthweight rats (F1) but diet does not modify the insulin resistance of their offspring (F2)

We examined the effects of prenatal and postnatal nutrition on birthweight and insulin sensitivity, indicated by the glucose/insulin (G/I) ratio, in adult rats (F1 generation) and in their adult offspring (F2 generation). Rat pups (F1) whose dams consumed low-protein diets during gestation (malnourished) consumed either nutritionally adequate (control) or high-fat diets ad libitum post-weaning. The offspring of these rats (F2) were maintained on the same diets as their respective dams. Separate pups (F1) whose dams consumed high-fat diets during gestation (over-nourished) were maintained on high-fat diets post-weaning, as were their offspring (F2). Birthweights were significantly reduced in all fetally malnourished F1 animals. At ∼70 d of age, fasting insulin sensitivity in over-nourished F1 rats was significantly reduced compared to controls regardless of whether they were malnourished or over-nourished in utero; however, fetally malnourished F1 rats consuming control diets post-natally had significantly greater fasting insulin sensitivity than control animals. At 30 and 120 min post-glucose load, insulin sensitivity was reduced 12-65% in both groups of over-nourished F1 rats as compared to the fetally malnourished F1 rats consuming the control diet. Birthweights were significantly lower in F2 animals whose dams (F1) were fetally malnourished and weaned to high fat diets. Insulin sensitivity was significantly reduced in all F2 animals versus control animals, regardless of dietary treatment. Thus, post-natal diets alter insulin sensitivity in fetally malnourished, adult rats; and maternal malnutrition during gestation results in insulin resistance in offspring, irrespective of offsprings' birthweight or diet.