The association between TNF-α and insulin resistance in euglycemic women.

Chronic low levels of inflammation have links to obesity, diabetes and insulin resistance. We sought to assess the relationship between cytokine tumor necrosis factor (TNF-α) and insulin resistance in a healthy, euglycemic population. This is a prospective study of 574 non-diabetic mother and infant pairs. Maternal body mass index (BMI), TNF-α, glucose and insulin were measured in early pregnancy and at 28 weeks. Insulin resistance was calculated by HOMA index. At delivery birthweight was recorded and cord blood analysed for fetal C-peptide and TNF-α. In a multivariate model, maternal TNF-α in early pregnancy was predicted by maternal insulin resistance at the same time-point, (ß=0.54, p<0.01), and maternal TNF-α at 28 weeks was predicted by maternal insulin resistance in early pregnancy (ß=0.24, p<0.01) and at 28 weeks (ß=0.39, p<0.01). These results, in a large cohort of healthy, non-diabetic women have shown that insulin resistance, even at levels below those diagnostic of gestational diabetes, is associated with maternal and fetal inflammatory response. These findings have important implications for defining the pathways of fetal programming of later metabolic syndrome and childhood obesity.

The influence of a low glycemic index dietary intervention on maternal dietary intake, glycemic index and gestational weight gain during pregnancy: a randomized controlled trial.

BACKGROUND: Maternal diet is known to impact pregnancy outcome. Following a low glycemic index (GI) diet during pregnancy has been shown to improve maternal glycemia and reduce infant birthweight and may be associated with a higher fibre intake. We assessed the impact of a low GI dietary intervention on maternal GI, nutritional intake and gestational weight gain (GWG) during pregnancy. Compliance and acceptability of the low GI diet was also examined. METHOD: Eight hundred women were randomised in early pregnancy to receive low GI and healthy eating dietary advice or to receive standard maternity care. The intervention group received dietary advice at a group education session before 22 weeks gestation. All women completed a 3 day food diary during each trimester of pregnancy. Two hundred and thirty five women from the intervention arm and 285 women from the control arm returned complete 3x3d FDs and were included in the present analysis. RESULTS: Maternal GI was significantly reduced in the intervention group at trimester 2 and 3. The numbers of women within the lowest quartile of GI increased from 37% in trimester 1 to 52% in trimester 3 (P < 0.001) among the intervention group. The intervention group had significantly lower energy intake (P < 0.05), higher protein (% TE) (P < 0.01) and higher dietary fibre intake (P < 0.01) post intervention. Consumption of food groups with known high GI values were significantly reduced among the intervention group. Women in the intervention low GI group were less likely to exceed the Institute of Medicine's GWG goals. CONCLUSION: A dietary intervention in early pregnancy had a positive influence on maternal GI, food and nutrient intakes and GWG. Following a low GI diet may be particularly beneficial for women at risk of exceeding the GWG goals for pregnancy.

Maternal Nutrition and Glycaemic Index during Pregnancy Impacts on Offspring Adiposity at 6 Months of Age--Analysis from the ROLO Randomised Controlled Trial.

Childhood obesity is associated with increased risk of adult obesity and metabolic disease. Diet and lifestyle in pregnancy influence fetal programming; however the influence of specific dietary components, including low glycaemic index (GI), remains complex. We examined the effect of a maternal low GI dietary intervention on offspring adiposity at 6 months and explored the association between diet and lifestyle factors in pregnancy and infant body composition at 6 months. 280 6-month old infant and mother pairs from the control (n = 142) and intervention group (n = 138), who received low GI dietary advice in pregnancy, in the ROLO study were analysed. Questionnaires (food diaries and lifestyle) were completed during pregnancy, followed by maternal lifestyle and infant feeding questionnaires at 6 months postpartum. Maternal anthropometry was measured throughout pregnancy and at 6 months post-delivery, along with infant anthropometry. No difference was found in 6 months infant adiposity between control and intervention groups. Maternal trimester three GI, trimester two saturated fats and trimester one and three sodium intake were positively associated with offspring adiposity, while trimester two and three vitamin C intake was negatively associated. In conclusion associations were observed between maternal dietary intake and GI during pregnancy and offspring adiposity at 6 months of age.

Leptin, fetal growth and insulin resistance in non-diabetic pregnancies.

BACKGROUND: Interrogation of the association between leptin, insulin resistance and fetal growth may provide a biological link for the fetal programming of later metabolic health. AIMS: Our aim was to clarify the relationship between maternal and fetal leptin, insulin resistance and fetal growth. STUDY DESIGN: Maternal leptin, glucose and insulin were measured in early pregnancy and at 28weeks and the HOMA index calculated. At 34weeks, ultrasound scan assessed fetal weight and adiposity (abdominal wall width). At delivery birthweight was recorded and cord blood analyzed for fetal c-peptide and leptin. Analysis was performed using a multivariate linear regression model. SUBJECTS: 574 non-diabetic pregnant women. OUTCOME MEASURES: Fetal growth and maternal and fetal insulin resistance. RESULTS: On multivariate analysis a relationship was identified between maternal and fetal leptin concentrations at each time point and maternal body mass index. Maternal leptin was related to insulin resistance in early pregnancy (ß=0.15, p=0.02) and at 28week gestation (ß=0.27, p<0.001). Fetal insulin resistance correlated with maternal leptin in early pregnancy (ß=0.17, p=0.004); at 28weeks (ß=0.12, p=0.05), and with leptin in cord blood (r=0.28, p<0.001). Fetal weight at 34weeks was related to maternal leptin in early pregnancy (ß=0.16, p=0.02). Both maternal and fetal leptin correlated with infant size at birth (ß=0.12, p=0.07 in early pregnancy, ß=0.21, p=0.004 in cord blood), independent of all other outcome measures. CONCLUSION: Our findings have confirmed that in a non-diabetic cohort there is a link between maternal and fetal leptin and insulin resistance. We also established a link between maternal leptin in early pregnancy and both fetal and neonatal size. These results add to the growing body of evidence suggesting a role for leptin in the fetal programming of childhood obesity and metabolic dysfunction.

The association of maternal and fetal glucose homeostasis with fetal adiposity and birthweight.

OBJECTIVE: To examine the association between maternal and fetal glucose levels and fetal adiposity and infant birthweight. STUDY DESIGN: This is a prospective study of 479 healthy, non-diabetic mother and infant pairs attending the National Maternity Hospital in Ireland. Fasting glucose was measured in early pregnancy (11.8±2.3 weeks). At 28 weeks gestation a repeat fasting glucose was measured and 1h glucose challenge testing (1h GCT) was performed. At 34 weeks' gestation (33+5-34+5 weeks) fetal growth and fetal anterior abdominal wall width, a marker of fetal adiposity, were measured. At delivery cord glucose was measured and neonatal anthropometry recorded. RESULTS: There was a positive correlation between fasting glucose concentration during pregnancy and both infant birthweight and fetal anterior abdominal wall width at 34 weeks gestation. The incidence of macrosomia (birthweight>4.5kg) was significantly greater for maternal and cord blood glucose levels in the highest quartile compared to the lowest quartile (20.7% vs. 11.7%, p<0.05 in the first trimester, 21.3% vs. 7.2%, p<0.05, at 28 weeks, and 33.3% vs. 10%, p<0.05, in cord blood). Maternal glucose concentrations at each time point, though not cord glucose, were related to early pregnancy maternal body mass index (r=0.19, p<0.001 in first trimester, r=0.25, p<0.001 at 28 weeks, r=0.15, p<0.01 with 1h GCT). CONCLUSION: Maternal glucose homeostasis is an important determinant of fetal size. We have shown that even small variations in fasting glucose concentrations can influence fetal growth and adiposity. This effect is seen from the first trimester and maintained until delivery.