Postnatal Pancreatic Islet β Cell Function and Insulin Sensitivity at Different Stages of Lifetime in Rats Born with Intrauterine Growth Retardation

Epidemiological studies have linked intrauterine growth retardation (IUGR) to the metabolic diseases, consisting of insulin resistance, type 2 diabetes, obesity and coronary artery disease, during adult life. To determine the internal relationship between IUGR and islet β cell function and insulin sensitivity, we established the IUGR model by maternal nutrition restriction during mid- to late-gestation. Glucose tolerance test and insulin tolerance test(ITT) in vivo and glucose stimulated insulin secretion(GSIS) test in vitro were performed at different stages in IUGR and normal groups. Body weight, pancreas weight and pancreas/body weight of IUGR rats were much lower than those in normal group before 3 weeks of age. While the growth of IUGR rats accelerated after 3 weeks, pancreas weight and pancreas/body weight remained lower till 15 weeks of age. In the newborns, the fasting glucose and insulin levels of IUGR rats were both lower than those of controls, whereas glucose levels at 120 and 180 min after glucose load were significantly higher in IUGR group. Between 3 and 15 weeks of age, both the fasting glucose and insulin levels were elevated and the glucose tolerance was impaired with time in IUGR rats. At age 15 weeks, the area under curve of insulin(AUCi) after glucose load in IUGR rats elevated markedly. Meanwhile, the stimulating index of islets in IUGR group during GSIS test at age 15 weeks was significantly lower than that of controls. ITT showed no significant difference in two groups before 7 weeks of age. However, in 15-week-old IUGR rats, there was a markedly blunted glycemic response to insulin load compared with normal group. These findings demonstrate that IUGR rats had both impaired pancreatic development and deteriorated glucose tolerance and insulin sensitivity, which would be the internal causes why they were prone to develop type 2 diabetes

Effects of altitude versus economic status on birth weight and body shape at birth

The compelling evidence linking small size at birth with later cardiovascular disease has renewed and amplified a clinical and scientific interest in the determinants of fetal growth. Although the effects of maternal nutrition on fetal growth have been extensively studied, comparatively little is known about the effects of maternofetal hypoxia. This study tested the hypothesis that in highland regions, high altitude rather than maternal economic status is associated with reduced and altered fetal growth by investigating the effects of high altitude versus economic status on birth weight and body shape at birth in Bolivia. Bolivia is geographically and socioeconomically unique. It contains several highland (>3500 m above sea level) and lowland (<500 m) cities that are inhabited by very economically divergent populations. Birth weight, body length, and head circumference were compared between a high- (n = 100) and low- (n = 100) income region of La Paz (3649 m; largest high-altitude city) and a high- (n = 100) and low- (n = 100) income region of Santa Cruz (437 m; largest low-altitude city). In addition, the frequency distribution across the continuum of birth weights was plotted for babies born from high- and low-income families in La Paz and Santa Cruz. Mean birth weights were lower in babies from La Paz than in babies from Santa Cruz in both high- and low-income groups. The cumulative frequency curve across all compiled birth weights was shifted to the left in babies from La Paz compared with those from Santa Cruz, regardless of economic status. The frequency of low birth weight (<2500 g) was higher in babies from La Paz than from Santa Cruz in both high- and low-income groups. In addition, at high altitude but not at low altitude, high income was associated with an increase in the head circumference:birth weight ratio. These findings suggest that high altitude rather than economic status is associated with low birth weight and altered body shape at birth in babies from Bolivia