A Thin Phenotype Is Protective for Impaired Glucose Tolerance and Related to Low Birth Weight in Mice

BackgroundLow birth weight is an independent risk factor for impaired glucose tolerance (IGT) and diabetes in adult life. This risk extends to both preterm and term infants, a particularly important finding given the increased survival of low-birth-weight infants with improvements in neonatal care. One potential strategy for prevention of low-birth-weight-associated glucose intolerance is postnatal nutritional modification and prevention of early postnatal weight gain. To determine the efficacy of this approach, we utilized our mouse model of low birth weight related to maternal undernutrition during the third week of pregnancy.MethodsWe studied three experimental groups of offspring mice: controls (C), undernutrition with low birth weight (UN) fed ad lib postnatally, and undernutrition with food restriction continued in postnatal life (UN-UN). Mean birth weight was significantly reduced in both groups of undernutrition offspring in utero (C: 1.86 ± 0.03 vs. UN: 1.37 ± 0.04 and UN-UN: 1.32 ± 0.06, p <0.001). As expected, and in accord with human data, differences in weight between C and UN mice disappeared by week 2 of life, indicating catch-up growth in the UN group.ResultsBody weight was similar in all groups until 4 months of age, after which the UN-UN group had reduced body weight as compared with controls (p <0.05 at 6 months). Insulin tolerance test (1 U/kg), glucose tolerance test (2 g/kg) and glucose-stimulated insulin secretion test (3 g/kg) at 2 months of age were identical among C, UN, and UN-UN groups. By age 6 months, IGT had developed in the UN mice (p <0.05 vs. C). By contrast, UN offspring with caloric restriction postnatally (UN-UN) were protected from the development of glucose intolerance, with glucose levels identical to that of control mice. These differences appeared to be related to improved insulin sensitivity in the UN-UN mice as compared with UN mice, although data did not reach statistical significance.ConclusionsOur data suggest that alterations in early postnatal nutrition are associated with prevention of weight gain and the development of IGT in low-birth-weight mice.