BACKGROUND: In-utero under-nutrition dramatically alters the development of adipose tissue, during the fetal and the neonatal period. THE AIM OF THE STUDY: To investigate whether adults born with intra-uterine growth retardation (IUGR) show evidence of impaired adipose tissue development and leptin regulation. DESIGN: Serum leptin concentrations were measured in 26 healthy adults born with IUGR and 25 controls aged 24 y who have been studied previously, 3 y ago. RESULTS:The IUGR group demonstrated a signi®cant increase of body mass index (BMI) in comparison to controls between 21 and 24 y of age (4.8 AE 7.7%, P 0.004 vs 0.8 AE 6.7%, P 0.70). Percentage of total body fat mass was signi®cantly higher in IUGR-born subjects than in controls (27.2 AE 7.6 vs 22.0 AE 7.3%, P 0.02). Fasting insulin was signi®cantly higher in the IUGR group (7.5 AE 3.8 vs 5.3 AE 2.3 mUaml, P 0.03). Surprisingly, crude serum leptin concentrations did not signi®cantly differ between the two groups. Moreover, adjusted means of serum leptin levels were signi®cantly lower in IUGR-born subjects than in controls when corrected for body fat mass, gender and fasting insulin (11.3 vs 13.8 ngaml, P 0.02). SUMMARY: Adults born with IUGR developed an excess of adipose tissue associated with relatively low serum leptin levels suggestive of an altered adipocyte function. Considering the close relationship between adipose tissue and insulin-sensitivity, these observations point to the potential implication of abnormal adipose tissue development in the long-term metabolic consequences associated with in-utero undernutrition.

In a case-control study that investigated the effect of intrauterine growth retardation (IUGR) on glucose homeostasis, 20-yr-old adults born with IUGR were shown to be hyperinsulinemic in an oral glucose tolerance test, suggestive of insulin resistance. The aim of this study was to ascertain the decreased insulin sensitivity in young IUGR-born adults compared to that in controls. We studied 26 IUGR-born subjects and 25 controls, aged 25 yr. Insulin sensitivity was assessed by peripheral glucose uptake and monitoring free fatty acid (FFA) concentrations under euglycemic hyperinsulinemic clamp. The percent body fat was significantly higher in the IUGR group (27.2 +/- 7.6% vs. 22.0 +/- 7.3%; P = 0.02), contrasting with comparable body mass index in both groups. Insulin-stimulated glucose uptake was significantly lower in IUGR-born subjects than in controls (6.7 +/- 2.9 vs. 8.0 +/- 1.9 mg/kg fat-free mass x min; P = 0.05), and the difference remained significant after adjustment for body mass index, total body fat, or waist to hip ratio. In IUGR-born subjects, insulin-stimulated FFA suppression correlated significantly with peripheral glucose uptake (r2 = 0.23; P = 0.02). First phase insulin release in the iv glucose tolerance test, adjusted for insulin sensitivity, did not significantly differ between IUGR and control groups (442 +/- 284 vs. 391 +/- 209 pmol/L; P = 0.86). In conclusion, IUGR subjects have decreased insulin-stimulated glucose uptake as early as 25 yr of age without major impairment of insulin secretion. Low glucose uptake is associated with a lesser degree of FFA suppression in adipose tissue, which suggests a role of adipose tissue at an early stage of insulin resistance in these subjects.