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Thomas Harder

Publications and source records attributed to Thomas Harder.

At least 19 recordsLinked to original sources

Birth weight and subsequent risk of type 2 diabetes: a meta-analysis.

The "small baby syndrome hypothesis" suggests that an inverse linear relation exists between birth weight and risk of type 2 diabetes. The authors conducted a meta-analysis to examine this association. They included studies that reported odds ratios and 95% confidence intervals (or data with which to calculate them) for the association of type 2 diabetes with birth weight. Fourteen studies involving a total of 132,180 persons were identified. Low birth weight (<2,500 g), as compared with a birth weight of >/=2,500 g, was associated with increased risk of type 2 diabetes (odds ratio (OR) = 1.32, 95% confidence interval (CI): 1.06, 1.64). High birth weight (>4,000 g), as compared with a birth weight of </=4,000 g, was associated with increased risk to the same extent (OR = 1.27, 95% CI: 1.01, 1.59). Pooled estimates increased further when normal birth weight (2,500-4,000 g) was used as the reference category (low birth weight: OR = 1.47, 95% CI: 1.26, 1.72; high birth weight: OR = 1.36, 95% CI: 1.07, 1.73). Meta-regression and categorical analyses showed a U-shaped relation between birth weight and diabetes risk. These findings indicate that there exists a relation between birth weight and later-life risk of type 2 diabetes which is not linearly inverse but U-shaped.

Birth Weight↗

Impact of breast-feeding on psychomotor and neuropsychological development in children of diabetic mothers: role of the late neonatal period.

AIM: Previous data from our Kaulsdorf Cohort Study (KCS) suggest that early neonatal ingestion (1st week) of breast milk from diabetic mothers (diabetic breast milk, DBM) may increase the risk of being overweight and delay speech development in offspring of diabetic mothers (ODM). Late neonatal DBM ingestion (2nd-4th week), however, not independently influenced the risk of overweight. We investigated whether late neonatal DBM ingestion might independently influence neuro-development. METHODS: Achievement of developmental milestones according to late neonatal DBM intake was analyzed in 242 ODM. RESULTS: No impact of DBM ingestion on psychomotor parameters was observed. In contrast, it negatively influenced onset of speaking (no DBM: median 44.0 weeks, range 31.0-72.0; some DBM: 48.0, 24.0-100.0; DBM only: 52.0, 28.0-84.0; P=0.037) and halved the probability of reaching this milestone at any time point (hazard ratio: 0.53, 95% confidence interval: 0.31-0.91). However, adjustment for DBM volume ingested during the early neonatal period weakened the hazard ratio towards non-significance. In the fully adjusted model, the hazard ratio was halved, but insignificant. CONCLUSIONS: Our results underscore that neonatal DBM ingestion, particularly during the first week of life, may delay speech development, an important indicator of cognitive development. Further studies are urgently recommended on consequences of breast-feeding for neurodevelopment in ODM.

Adult↗

Condensation of the plasma membrane at the site of T lymphocyte activation.

After activation, T lymphocytes restructure their cell surface to form membrane domains at T cell receptor (TCR)-signaling foci and immunological synapses (ISs). To address whether these rearrangements involve alteration in the structure of the plasma membrane bilayer, we used the fluorescent probe Laurdan to visualize its lipid order. We observed a condensation of the plasma membrane at TCR activation sites. The formation of ordered domains depends on the presence of the transmembrane protein linker for the activation of T cells and Src kinase activity. Moreover, these ordered domains are stabilized by the actin cytoskeleton. Membrane condensation occurs upon TCR stimulation alone but is prolonged by CD28 costimulation with TCR. In ISs, which are formed by conjugates of TCR transgenic T lymphocytes and cognate antigen-presenting cells, similar condensed membrane phases form first in central regions and later at the periphery of synapses. The formation of condensed membrane domains at T cell activation sites biophysically reflects membrane raft accumulation, which has potential implications for signaling at ISs.

Animals↗

Duration of breastfeeding and risk of overweight: a meta-analysis.

Observational studies suggest a longer duration of breastfeeding to be associated dose dependently with a decrease in risk of overweight in later life. The authors performed a comprehensive meta-analysis of the existing studies on duration of breastfeeding and risk of overweight. Studies were included that reported the odds ratio and 95% confidence interval (or the data to calculate them) of overweight associated with breastfeeding and that reported the duration of breastfeeding and used exclusively formula-fed subjects as the referent. Seventeen studies met the inclusion criteria. By meta-regression, the duration of breastfeeding was inversely associated with the risk of overweight (regression coefficient=0.94, 95% confidence interval (CI): 0.89, 0.98). Categorical analysis confirmed this dose-response association (<1 month of breastfeeding: odds ratio (OR)=1.0, 95% CI: 0.65, 1.55; 1-3 months: OR=0.81, 95% CI: 0.74, 0.88; 4-6 months: OR=0.76, 95% CI: 0.67, 0.86; 7-9 months: OR=0.67, 95% CI: 0.55, 0.82; >9 months: OR=0.68, 95% CI: 0.50, 0.91). One month of breastfeeding was associated with a 4% decrease in risk (OR=0.96/month of breastfeeding, 95% CI: 0.94, 0.98). The definitions of overweight and age had no influence. These findings strongly support a dose-dependent association between longer duration of breastfeeding and decrease in risk of overweight.

Breast Feeding↗

Independent association between leptin and blood pressure during third trimester in normal and gestational diabetic pregnancies.

OBJECTIVE: To assess the relationship between plasma leptin concentration during third trimester of pregnancy and blood pressure, independent of body mass index at examination and other potential confounders. STUDY DESIGN: A cross-sectional study was performed including 95 women (61 non-diabetic women, 34 women with gestational diabetes (GD)) in their third trimester of pregnancy. The relationship between plasma leptin and blood pressure was investigated using multiple linear regression analysis. RESULTS: Independent of body mass index (BMI), leptin was positively correlated to systolic (P = 0.024) and diastolic blood pressure (P = 0.002). Stepwise linear regression identified leptin as the only variable independently associated with systolic blood pressure (P = 0.003), while leptin (P < 0.001) and age (P = 0.024) were the only variables independently correlated to diastolic blood pressure. CONCLUSIONS: This study reports for the first time that, independent of BMI at examination, presence of GD or other confounders, plasma leptin is positively correlated with blood pressure in pregnant women.

Blood Pressure↗

'Programming' of orexigenic and anorexigenic hypothalamic neurons in offspring of treated and untreated diabetic mother rats.

Exposure to maternal diabetes in utero (GD) may 'program' for obesity. Orexigenic neuropeptides, like neuropeptide Y (NPY) and agouti-related peptide (AGRP), and anorexigenic neuropeptides, like proopiomelanocortin (POMC) and alpha-melanocyte-stimulating hormone (MSH), are decisively involved in body weight regulation. We investigated consequences of GD and its treatment by pancreatic islet transplantation in rats for development of neuropeptidergic neurons in the arcuate hypothalamic nucleus (ARC) in weanling offspring. In GD, islet transplantation on d15 of pregnancy led to normalized blood glucose. Sham-transplanted GD mothers (TSGD) remained hyperglycemic. Twenty-one-day-old TSGD offspring developed hypothalamic 'malorganization'. Despite of normal leptin and insulin levels in TSGD offspring, increased immunopositivity of NPY and AGRP appeared. TSGD offspring showed unchanged POMC, but decreased MSH-immunopositivity. In conclusion, untreated diabetes in pregnant rats leads to 'malprogramming' of hypothalamic neuropeptidergic neurons in offspring, probably contributing to later development of overweight. These acquired alterations are preventable by treatment of maternal GD.

Animals↗

Impact of early neonatal breast-feeding on psychomotor and neuropsychological development in children of diabetic mothers.

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 = 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 = 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 breast-feeding in ODM.

Adult↗

Long-term impact of breast-feeding on body weight and glucose tolerance in children of diabetic mothers: role of the late neonatal period and early infancy.

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 = 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 = 0.004) and 120-min blood glucose during an oral glucose tolerance test (P = 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.

Adult↗

Birth weight and parental BMI predict overweight in children from mothers with gestational diabetes.

OBJECTIVE: To investigate the growth of children from pregnancies with gestational diabetes mellitus (GDM) and its association with antenatal maternal, fetal, and recent anthropometric parameters of mother and father. RESEARCH DESIGN AND METHODS: In 324 pregnancies of Caucasian women with GDM, BMI before pregnancy, maternal glycemic values, and measurements of the fetal abdominal circumference were recorded. The weight and height of infants were measured at birth and at follow-up at 5.4 years (range 2.5-8.5). In addition, somatic data from routine examinations at 6, 12, and 24 months and the BMI of parents at follow-up were obtained. BMI standard deviation scores (SDSs) were calculated based on age-correspondent data. RESULTS: At all time points, BMI was significantly above average (+0.82 SDS at birth; +0.56 at 6, +0.35 at 12, and +0.32 at 24 months; and +0.66 at follow-up; P < 0.001). BMI at birth was related to BMI at follow-up (r = 0.27, P < 0.001). The rate of overweight at follow-up was 37% in children with birth BMI > or =90th percentile and 25% in those with normal BMI at birth (P < 0.05). Abdominal circumference of third trimester and postprandial glucose values were related to BMI at follow-up (r = 0.22 and r = 0.18, P < 0.01). Recent maternal, paternal, and birth BMI were independent predictors of BMI at follow-up (r = 0.42, P < 0.001). Sixty-nine percent of children of parents with BMI > or =30 kg/m(2) were overweight at follow-up compared with 20% of those with parental BMI <30 kg/m(2) (P < 0.001). CONCLUSIONS: Children of mothers with GDM have a high rate of overweight that is associated both with intrauterine growth and parental obesity.

Anthropometry↗

CT and MRI in haemolytic uraemic syndrome with central nervous system involvement: distribution of lesions and prognostic value of imaging findings.

BACKGROUND: Central nervous system (CNS) involvement is a common complication in haemolytic uraemic syndrome (HUS). Various imaging findings have been described, mostly as case reports. Although there are a few retrospective studies on larger patient groups there is no report that focuses on MRI. OBJECTIVE: To analyse the CT and MRI studies of patients with neurological complications of HUS, to describe the typical imaging findings, and to evaluate their predictive character with regard to follow-up examinations and clinical outcome. MATERIALS AND METHODS: Of 57 patients with clinically proven HUS who were referred to our hospital between 1995 and 2003, 17 had signs of serious CNS involvement and 10 underwent neuroimaging. Nine MRI and seven CT studies were performed in the acute phase and five MRI and two CT studies were done for follow-up. RESULTS: In six patients, pathological imaging findings were seen on CT or MRI performed in the acute phase of the disease whereas CT and MRI scans were completely normal in four patients. All patients with positive imaging findings had pathological changes within the basal ganglia. Additional findings were seen in the thalami (n=2), cerebellum (n=2) and brain stem (n=1). On follow-up imaging performed in five cases, the pathological imaging findings had resolved completely in two and partially in three patients. All patients had a good neurological outcome. Comparing the various MRI findings, a haemorrhagic component within an acute lesion was the most reliable parameter predicting residual pathologic findings on follow-up imaging. CONCLUSIONS: Basal ganglia involvement is a typical finding in patients with neurological complications of HUS. Even in patients with severe CNS involvement on acute imaging studies, prognosis was favourable for clinical outcome and resolution of pathological imaging findings.

Central Nervous System Diseases↗