Abstract P191: Higher Levels of Tumor Necrosis Factor Alpha are Associated with Elevated Insulin Resistance during Pregnancy and Increased Risk of Gestational Diabetes Mellitus
Background: Gestational diabetes mellitus (GDM) results from an imbalance between insulin resistance and insulin secretion capacity during pregnancy. Tumor Necrosis Factor alpha (TNFα), a cytokine produced by adipose tissue and the placenta, seems to be involved in insulin resistance development. Higher levels of TNFα have been associated with insulin resistance in non-pregnant populations, but reports on its potential role in glycemic regulation during pregnancy have been inconsistent.
Aims: To determine if TNFα levels are associated with GDM and with insulin resistance during pregnancy.
Methods: A population-based cohort of pregnant women was evaluated between 24 and 28 weeks of gestation using standardized anthropometric measurements, medical questionnaires, and a standard 75g oral glucose tolerance test (OGTT). GDM diagnosis was based on the International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria. Additional blood samples were collected to measure insulin and TNFα levels (by ELISA). Insulin sensitivity was estimated by the Matsuda index; insulin secretion was estimated by the ratio of area under the curve of insulin/glucose (AUC ins/gluc).
Results: This analysis included 523 pregnant women who were representative of our population (age= 28.3±4.4 years old; 96% of European descent, body mass index (BMI)= 27.9±5.4 kg/m2). Based on OGTT at 27 weeks, 478 women showed normal glucose tolerance (NGT) and 45 women developed GDM (incidence = 8.6%). Pregnant women with GDM had higher fasting TNFα levels (GDM=2.09 [1.38-2.67] pg/ml; NG=1.53 [1.03-2.26] pg/ml; p=0.01). Mean TNFα levels decreased over the course of the OGTT (fasting=1.80 pg/ml; 1h=1.65 pg/ml; 2h=1.55 pg/ml). Higher fasting TNFα levels were associated with lower insulin sensitivity assessed by Matsuda index (r= -0.34; p<0.0001) and this association remained significant after adjustment for age, adiposity measurements (BMI or percent body fat), lipid profile (triglycerides and LDL levels), and AUC ins/gluc (p<0.0001).
Conclusion: Higher TNFα levels at 2nd trimester are associated with lower insulin sensitivity independently of age, adiposity and insulin secretion in a prospective population-based cohort. Thus, TNFα could be involved in the pathophysiological processes leading to GDM through insulin resistance pathways.
- © 2013 by American Heart Association, Inc.