Fetuses of obese mothers develop insulin resistance in utero

Abstract

Objective: Offspring of obese mothers have an increased risk for obesity and diabetes. The purpose of this study was to determine whether fetuses of obese women have increased obesity, insulin resistance, and markers of inflammation, supporting the concept of fetal programming.

Research design and methods: Fifty-three lean and 68 obese women with singleton term pregnancies were evaluated at elective cesarean delivery. Maternal and umbilical cord blood was obtained for measures of insulin resistance and cytokines. Neonatal body composition was estimated using anthropometric measurements within 24 h of delivery.

Results: The fetuses of obese mothers had greater percent body fat (13.1 +/- 3.4 vs. 11.6 +/- 2.9%, P = 0.02), homeostasis model assessment of insulin resistance (1.51 +/- 0.86 vs. 1.06 +/- 0.70, P = 0.003), cord leptin (14.5 +/- 13.5 vs. 8.2 +/- 4.7 ng/ml, P = 0.001), and interleukin-6 (3.5 +/- 2.3 vs. 2.4 +/- 1.4 pg/ml, P = 0.02) than fetuses of lean women. There was a strong positive correlation between fetal adiposity and insulin resistance (r = 0.32, P = 0.0008) as well as maternal pregravid BMI and fetal insulin resistance (r = 0.31, P = 0.007) even with adjustment for potential confounders. Cord leptin had a significant correlation with fetal insulin resistance (r = 0.30, P = 0.001), but there was no significant correlation between any other umbilical cord cytokines and fetal insulin resistance.

Conclusions: These data suggest that maternal obesity creates a significant risk for the next generations with metabolic compromise already apparent at birth. Therefore, if prevention of obesity is the goal rather than treatment, the perinatal period may be an important focus of future research.

Figure 1

HOMA-IR indexes in fetuses of lean and obese mothers. A: The fetuses of obese mothers have higher HOMA-IR indexes, i.e., they are more insulin resistant than those of lean mothers. The lower HOMA-IR values in offspring compared with mothers are indicative of higher insulin sensitivity in utero. B: Regression analysis shows a positive correlation between maternal (Mat) and fetal insulin resistance. ○, lean (BMI <25 kg/m²); ●, obese (BMI >30 kg/m²). Data are means ± SEM. *P < 0.003 and **P < 0.0001 versus lean. □, lean women and fetuses of lean women; , obese women and fetuses of obese women.

Figure 2

Relationship of fetal insulin with fetal adiposity. Regression analyses show a positive correlation between fetal insulin resistance estimated by HOMA-IR at birth and percent neonatal body fat of the fetus.