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, (β=0.54, p<0.01), and maternal TNF-α at 28 weeks was predicted by maternal insulin resistance in early pregnancy (β=0.24, p<0.01) and at 28 weeks (β=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.