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Exposure to maternal gestational diabetes (GD) "programs" offspring for obesity in childhood and later life. Recent clinical data suggest that neonatal ingestion of breast milk from diabetic mothers might be crucially involved. Mediobasal hypothalamic nuclei such as the ventromedial nucleus (VMN), the paraventricular nucleus (PVN) and the arcuate nucleus (ARC) play a key role in the central nervous system regulation of food intake and body weight. In the ARC, orexigenic neuropeptides such as neuropeptide Y (NPY), galanin (GAL), and agouti-related peptide (AGRP) and anorexigenic neuropeptides such as proopiomelanocortin (POMC) and alpha-melanocyte-stimulating hormone (MSH) are expressed. We investigated the effects of neonatal exposure to milk from GD rat dams on the development of hypothalamic nuclei in weanling rats. Offspring of control (CO) rat dams cross-fostered to GD rat dams (CO-GD) developed early postnatal growth delay. On d 21 of life, CO-GD rats showed structural and functional hypothalamic "malprogramming." The ARC of CO-GD rats showed increased immunopositivity of both NPY and AGRP under basal conditions, despite normal levels of glucose, leptin, and insulin. Conversely, CO-GD rats showed decreased immunopositivity of both POMC and MSH and decreased density of immunopositive neurons, compared with offspring of control rat dams cross-fostered to control rat dams. No morphometric alterations were found in the VMN, whereas CO-GD rats showed an increased total number of neurons in the PVN. In summary, neonatal exposure to maternal diabetes through the intake of dam's milk in rats leads to a complex malprogramming of hypothalamic orexigenic and anorexigenic circuits that are critically involved in the lifelong regulation of food intake, body weight, and metabolism.

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OBJECTIVE -In general, breast-feeding positively influences development of psychomotor function and cognition in children. Offspring of diabetic mothers (ODM) have delayed psychomotor and cognitive development. Recently, we observed a dose-dependent negative effect of early neonatal ingestion of breast milk from diabetic mothers (diabetic breast milk [DBM]) on the risk of overweight during early childhood. Here, we investigated the influence of early neonatal intake of DBM on neurodevelopment in ODM. RESEARCH DESIGN AND METHODS-A total of 242 ODM were evaluated for age of achieving major developmental milestones (Denver Developmental Scale) according to the volume of DBM ingested during the first week of life, using Kruskal-Wallis and Kaplan-Meier analysis.RESULTS -Children in the upper tertile of early neonatal ingestion of DBM achieved early psychomotor developmental milestones ("lifting head while prone," "following with eyes") earlier than those in lower tertiles (P ϭ 0.002). In contrast, a delay in the onset of speaking was observed in children who had ingested larger volumes of DBM compared with those with lower DBM intake (P ϭ 0.002). This negative impact of DBM ingestion was not confounded by birth characteristics, total milk intake, or socioeconomic/educational status. CONCLUSIONS -Our data indicate differential effects of early neonatal DBM ingestion on psychomotor and cognitive development. Ingesting larger compared with smaller volumes of DBM may normalize early psychomotor development in ODM but delays onset of speaking as a parameter indicative of cognitive development. This effect may result from qualitative alterations in the composition of DBM. Further studies are urgently recommended on the benefits and harms of breastfeeding in ODM. Diabetes Care 28:573-578, 2005B reast-feeding is the best way to nurture healthy-term offspring of healthy mothers. It is well known to have positive short-and long-term effects, e.g., decreased risk of obesity or type 2 diabetes (1,2). Furthermore, evidence exists of a positive influence of breast feeding on psychomotor and cognitive development (3,4), persisting into adult age (5).Positive long-term effects of breastfeeding have been attributed to the composition of breast milk, including factors promoting neurodevelopment, such as long-chain polyunsaturated fatty acids (6). However, it has rarely been considered so far whether breast-feeding is still of advantage if the mother is affected by a noncommunicable disease, e.g., a metabolic disease, which may alter the composition of breast milk.Offspring of diabetic mothers (ODM) have delayed psychomotor and cognitive development (7-10). Pathophysiologic mechanisms remain unknown. Recently, we showed that early neonatal intake of breast milk from diabetic mothers may dose-dependently lead to an increased risk of overweight and impaired glucose tolerance during early childhood (11). Here, we evaluated whether the early neonatal intake of diabetic breast milk (DBM) may also influence cognitive and psychomotor developm...

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