Endocrine Pancreas Development in Growth-Retarded Human Fetuses

Abstract

Glucose intolerance in adults born with intrauterine growth retardation (IUGR) may involve peripheral insulin resistance and/or abnormal endocrine pancreas development during fetal life. We quantified insulincontaining cells in deceased human fetuses with IUGR (<10th percentile, n ‫؍‬ 21) or normal growth (control fetuses, n ‫؍‬ 15). Paraffin-embedded pancreatic tissues from fetuses older than 32 weeks were obtained from two fetopathology departments. Mean gestational age was 36 weeks in both groups. Tissues with lysis and those fetuses with defects, aneuploidy, or genetic abnormalities were excluded. For each subject, six pancreatic sections spaced evenly throughout the organ were immunostained with anti-insulin antibody. Total tissue and insulin-positive areas were measured by computer-assisted quantitative morphometry. Results were expressed in percentages. To evaluate islet morphogenesis, the percentages of ␤-cells inside and outside islets were determined. Islet density was similar in the two groups (P ‫؍‬ 0.86). The percentage of pancreatic area occupied by ␤-cells (␤-cell fraction) was not correlated with gestational age (r ‫؍‬ 0.06 and P ‫؍‬ 0.97 in IUGR fetuses; r ‫؍‬ 0.12 and P ‫؍‬ 0.67 in control fetuses) or body weight (r ‫؍‬ 0.16 and P ‫؍‬ 0.47 in IUGR fetuses; r ‫؍‬ 0.24 and P ‫؍‬ 0.39 in control fetuses). Mean ␤-cell fraction was 2.53% in the IUGR fetuses and 2.86% in the control fetuses (P ‫؍‬ 0.47). The percentage of ␤-cells located within islets was identical in the two groups (mean 35%). Our data militate against a primary developmental pancreatic abnormality in human IUGR, leaving peripheral insulin resistance as the most likely mechanism of glucose intolerance in adults born with IUGR. Diabetes 51:385-391, 2002

Decreased Fetal Size Is Associated With β-Cell Hyperfunction in Early Life and Failure With Age

“…Data for ␤-cell mass in humans with IUGR are inconsistent. One group reported a decrease (45) and another no change in islets from IUGR fetuses (46). These data are not directly comparable with our work because we studied mice near the end of gestation (E18.5), while human fetuses in both of these studies were analyzed early in the third trimester when islet morphogenesis is not complete.…”

Small for Gestational Age: Short Stature and Beyond

“…Additional confirmation that major ␤-cell dysfunction is not the primary defect associated with undernutrition in utero is provided by the work of Beringue et al (199). They found that ␤-cell morphology, islet density, and the percentage of pancreatic area occupied by ␤-cells were identical in fetuses born SGA and those born AGA.…”

Impact and Mechanisms of Pancreatic Beta-Cell Mass Programming by Maternal Diabetes - Insight from Animal Model Studies

“…This is consistent with the observation that pancreatic tissue taken from human fetuses with severe IUGR is characterized by a reduction in endocrine cell mass (Van Assche & Aerts, 1979). However this has not been confirmed since no difference was also found between IUGR and control human fetuses in insulin-positive area or islet organization during the last two months of pregnancy (Beringue et al, 2002).…”