Reductions in caloric intake and early postnatal growth prevent glucose intolerance and obesity associated with low birthweight.
OBJECTIVE
Low birthweight (LBW) and rapid postnatal weight gain, or catch-up growth, are independent risk factors for the development of obesity and diabetes during adult life. Individuals who are both small at birth and have postnatal catch-up growth are at the highest risk. We hypothesised that dietary interventions designed to attenuate catch-up growth in LBW subjects may have long-term beneficial consequences.


METHODS
We used our previously described mouse model of LBW-associated diabetes, created by restricting maternal food intake to 50% during the last week of gestation. Control (C) dams and dams that had been subjected to undernutrition (U) were then provided either chow ad libitum after delivery or 50% food restriction on a per-day basis from delivery until weaning. We designated the resulting four groups control-control (CC), undernutrition-control (UC), control-undernutriton (CU) and undernutrition-undernutrition (UU), indicating the prenatal and postnatal experimental conditions, respectively. Carbohydrate metabolism and adiposity were assessed prospectively in offspring until age 6 months.


RESULTS
Males that were small at birth and exhibited early postnatal catch-up growth developed glucose intolerance and obesity by age 6 months. In contrast, LBW mice without catch-up growth (UU) remained smaller than controls (CC), and glucose intolerance and obesity was prevented. Similarly, mice with normal birthweight that had blunted catch-up growth (CU) were leaner and had better tolerance test than CC mice. Catch-up growth during the first week of life correlated better than birthweight with glucose, fat mass and glucose tolerance up to 6 months of age.


CONCLUSIONS
Prevention of early catch-up growth reversed the development of glucose intolerance and obesity in our mouse model of LBW-associated diabetes.
Jimenez-Chillaron
J C
JC
Department of Cellular and Molecular Physiology, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USA.
Hernandez-Valencia
M
M
Lightner
A
A
Faucette
R R
RR
Reamer
C
C
Przybyla
R
R
Ruest
S
S
Barry
K
K
Otis
J P
JP
Patti
M E
ME
D004038:Diet, Reducing; D002149:Energy Intake; D018149:Glucose Intolerance / Q000453:epidemiology / Q000517:prevention & control*; D006128:Growth / Q000502:physiology*; D006801:Humans; D007223:Infant; D007230:Infant, Low Birth Weight / Q000502:physiology*; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D009765:Obesity / Q000453:epidemiology / Q000517:prevention & control*
D007328:Insulin; D020738:Leptin