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

Since Pedersen's fundamental work [1] the metabolic situation in infants of mothers with diabetes mellitus during pregnancy has been investigated in a number of studies [2][3][4]. While most authors focussed on altered glucose homeostasis during neonatal life, it remains unclear if these alterations do persist or resolve in later life. Clinical investigations during childhood indicated elevated frequencies of impaired glucose tolerance (IGT) in the offspring of mothers with diabetes during pregnancy [5,6]. Some authors reported alterations of insulin secretion such as hyperinsulinaemia [6,7] which is known to play a key role in the development of metabolic and cardiovascular disturbances in adulthood [8]. Experimental studies in rats displayed long-term alterations of glucose tolerance and insulin secretion due to the induction of maternal gestational hyperglycaemia which leads to fetal and neonatal hyperinsulinism [9][10][11][12][13].However, only a very small number of studies are available which compared glucose metabolism and Diabetologia (1997Diabetologia ( ) 40: 1094Diabetologia ( -1100 Glucose tolerance and insulin secretion in children of mothers with pregestational IDDM or gestational diabetes Summary The offspring of mothers with diabetes mellitus during pregnancy are presumed to develop altered glucose homeostasis. We analysed metabolic parameters at birth and glucose tolerance and insulin secretion during oral glucose tolerance tests at 1-9 years of age in 129 children born to mothers with pregestational insulin-dependent diabetes (IDDM) and 69 infants of gestational diabetic mothers. Newborns of IDDM mothers displayed higher insulin (p < 0.001), glucose (p < 0.05), and insulin/glucose ratios (p < 0.002) than newborns of gestational diabetic mothers. During childhood, frequencies of impaired glucose tolerance (IGT) rose in infants of IDDM mothers from 9.4 % at 1-4 years to 17.4 % at 5-9 years of age, while in children of gestational diabetic mothers an increase from 11.1 % up to 20.0 % was observed. Offspring of gestational diabetic mothers displayed higher stimulated blood glucose (p < 0.025) than infants of IDDM mothers, while children of IDDM mothers showed higher stimulated insulin (p < 0.025), accompanied by increased fasting and stimulated insulin/glucose ratios (p < 0.05 and p < 0.02, respectively). Stimulated insulin in childhood was positively correlated to insulin at birth (p < 0.05). Furthermore, insulin/glucose ratio in childhood showed a positive correlation to insulin (p < 0.01) and insulin/glucose ratio at birth (p < 0.005). In conclusion, a pathogenetic role of fetal and neonatal hyperinsulinism for the development of IGT in both groups of infants of diabetic mothers is suggested, in particular for early induction of insulin resistance in the offspring of mothers with pregestational IDDM. [Diabetologia (1997)

OBJECTIVES: To analyse the development of body weight and frequencies of overweight and obesity in infants of long-term insulin-dependent diabetic mothers as compared to those of gestational diabetic mothers. DESIGN: Retrospective study. SUBJECTS: Two hundred infants of mothers with pregestational insulin-dependent diabetes mellitus (IDM) and 117 infants of gestational diabetic mothers (IGDM) born between 1980 and 1990 at the Clinic of Obstetrics and Gynaecology, Berlin-Kaulsdorf, Germany. MEASUREMENTS: Birth weight, birth length, plasma insulin, interscapular skinfold, symmetry index (SI) and body mass index (BMI) at birth; SI and BMI in childhood (1±9 y of age). RESULTS: Neonatally, mean relative weight (SI) was found to be increased in both groups of infants. It was positively correlated to interscapular skinfold (P`0.001) and insulin (P`0.005). However, IDM had higher insulin levels (P`0.001) and a higher frequency of obesity (P`0.05) than IGDM at birth. Throughout childhood frequencies of overweight (SI b 1.1) were elevated in both IDM as well as IGDM. In IDM the percentage of obesity (SI b 1.2) displayed a signi®cant increase from 11.2% in children 1±4 y old up to 25.8% at 5±9 y (P`0.05). Similar frequencies and a highly signi®cant increase of overweight during childhood of IDM (P`0.005) were observed when BMI ! 95th percentile was used to determine overweight. Relative weight in childhood was positively correlated to relative weight at birth (P`0.05). Large-for-gestational-age infants displayed a signi®cantly higher percentage of overweight (SI b 1.1) in childhood than appropriate-for-gestational-age infants (P`0.05). CONCLUSIONS: Infants of mothers with diabetes during pregnancy are predisposed to develop overweight and obesity during childhood. These alterations seem to be related to insulin and relative body weight at birth. Pathophysiological mechanisms which might be involved into the development of these changes are discussed. Prophylactic measures are recommended to reduce morbidity in infants of diabetic mothers.

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...

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...