OBJECTIVE -Offspring born to women with pregnancies complicated by diabetes are at increased childhood risk of developing obesity and impaired glucose tolerance (IGT). In population-based studies, breast-feeding has been shown to be protective against obesity and diabetes later in life. To date, the role of breast-feeding on offspring of diabetic mothers (ODM) has not been investigated in this context. RESEARCH DESIGN AND METHODS-A total of 112 ODM (type 1 diabetes, n ϭ 83; gestational diabetes, n ϭ 29) were evaluated prospectively for impact of ingestion of either diabetic breast milk (DBM) or nondiabetic banked donor breast milk (BBM) during the early neonatal period (day 1-7 of life) on relative body weight and glucose tolerance at a mean age of 2 years.RESULTS -There was a positive correlation between the volume of DBM ingested and risk of overweight at 2 years of age (odds ratio [OR] 2.47, 95% CI 1.25-4.87). In contrast, the volume of BBM ingested was inversely correlated to body weight at follow-up (P ϭ 0.001). Risk of childhood IGT decreased by increasing amounts of BBM ingested neonatally (OR 0.19, 95% CI 0.05-0.70). Stepwise regression analysis showed volume of DBM to be the only significant predictor of relative body weight at 2 years of age (P ϭ 0.001).CONCLUSIONS -Early neonatal ingestion of breast milk from diabetic mothers may increase risk of becoming overweight and, consequently, developing IGT during childhood. Additional studies are needed to assess long-term consequences that might result from the type of neonatal nutrition in ODM. Diabetes Care 25:16 -22, 2002

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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.

OBJECTIVE -Offspring of diabetic mothers (ODM) are at increased risk of developing overweight and impaired glucose tolerance (IGT). Recently, we observed that early neonatal ingestion of breast milk from diabetic mothers (DBM) may dose-dependently increase the risk of overweight in childhood. Here, we investigate whether DBM intake during the late neonatal period and early infancy also influences later adipogenic and diabetogenic risk in ODM.RESEARCH DESIGN AND METHODS -A total of 112 ODM were evaluated for influence of DBM ingestion during the late neonatal period (2nd-4th neonatal week) and early infancy on relative body weight (RBW) and glucose tolerance in early childhood. RESULTS -Exclusive breast-feeding was associated with increased childhood RBW (P ϭ 0.011). Breast-fed ODM had an increased risk of overweight (odds ratio 1.98 [95% CI 1.12-3.50]). Breast-feeding duration was also positively related to childhood RBW (P ϭ 0.004) and 120-min blood glucose during an oral glucose tolerance test (P ϭ 0.022). However, adjustment for the DBM volume ingested during the early neonatal period, i.e., 1st week of life, eliminated all these relations with late neonatal breast-feeding and its duration. Interestingly, no relationship was observed between maternal blood glucose in the middle of the third trimester and the outcome.CONCLUSIONS -Neither late neonatal DBM intake nor the duration of breast-feeding has an independent influence on childhood risk of overweight or IGT in ODM. Therefore, the 1st week of life appears to be the critical window for nutritional programming in ODM by ingestion of maternal "diabetic" breast milk. Diabetes Care 28:1457-1462, 2005B reast feeding was variously shown to protect against later overweight and diabetes (1-6). This effect is attributed to differences in the composition of formula compared with breast milk (3). Offspring of diabetic mothers (ODM) are at increased risk of developing overweight and impaired glucose tolerance (IGT) even in childhood (7-10). Underlying mechanisms are still not understood. Clinical (8 -10) and experimental (11-13) studies have shown that a diabetic intrauterine environment plays a key role in programming of increased susceptibility to overweight and diabetes.We recently observed that ingestion of breast milk from diabetic mothers (diabetic breast milk; DBM) during the 1st neonatal week may dose-dependently lead to increased rather than decreased risk of overweight in later childhood of ODM (14). This lasting deleterious effect of DBM ingestion might result from altered macronutrient and hormonal milk composition (15-18).However, as the study addressed the early neonatal nutrition, results did not show whether breast-feeding after the 1st neonatal week also has any lasting influence. The vast majority of studies on the influence of breast-feeding on later disease risk ignored whether the mother was affected by a noncommunicable, i.e., metabolic disease, during lactation and, moreover, focused only on whether breast-feeding and/or the duration of breast-f...

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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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Animal studies have shown that prenatal exposure to a diabetic intrauterine milieu leads to an increased risk in the female offspring of developing gestational diabetes (GD). In the present study, the family history of non-insulin-dependent diabetes mellitus type II (NIDDM) and insulin-dependent diabetes mellitus type I (IDDM) was evaluated in 106 women with GD, as compared to 189 women with IDDM. In GD patients, the prevalence of diabetes was significantly greater in mothers than in fathers (p = 0.03). This was mainly due to a greater prevalence of NIDDM in the mothers (p = 0.05). Furthermore, a significant aggregation of NIDDM was also observed in the maternal-grandmaternal line of GD women, as compared to the paternal-grandpaternal side (p = 0.02). In patients with IDDM no significant difference concerning the prevalence of any type of diabetes between mothers and fathers was observed. In conclusion, an aggregation of NIDDM in mothers and grandmothers of women with GD is reported here. A history of NIDDM on the maternal side of pregnant women should be considered as a particular risk factor for GD and, hence, for intergenerative transmission of NIDDM, which therefore might be prevented, at least in part, by strict avoidance of GD.