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J Neurochem 2003 Feb84(3)417-31 Me
al size and frequency affect neuronal plasticity
and vulnerability to disease cellular and
molecular mechanisms.Mattson MP, Duan W, Guo
Z.Laboratory of Neurosciences, National
Institute on Aging, Gerontology Research Center,
Baltimore, Maryland 21224, USA.
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• (i) programming of body composition
• (ii) fetal determinants of immunity
• (iii) programming renal development
• cardiovascular disease and
• (iv) the regulatory mechanisms involved.

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Metabolic Programming

• Persistent changes in organ structure and/or
  function caused by exposure to adverse
  environmental influences during critical periods
  of development
• These adaptations result in higher risks for
  developing a variety of chronic diseases later in
  life, including Type 2 diabetes

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Organ Development
In utero
Organ Structure and Function at birth
Environment- Risk of disease expression
Genetics- Predisposition to disease
Early life
Hormonal and Metabolic Profiles
Alterations of Organ Structure/Function
Expression of Disease
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Genetic FactorsParental diabetes and birth
weight (Pimas) (from R. Lindsay et al. Diabetes
49 445,2000)
Mean birth wt (gm)
Overall diff between groups, plt 0.0001
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Organ Development
In utero (hormonal/metabolic)
Organ Structure and Function at birth
Environment- Risk of disease expression
Genetics- Predisposition to disease
Early life (feeding patterns)
Hormonal and Metabolic Profiles
Alterations of Organ Structure/Function
Expression of Disease
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Environmental factors First yearGrowth rates
and childhood obesity (N Stettler et al.
Pediatrics 109194,2002)

• Prospective cohort study among 12 US sites
• (n 19,397 followed from birth to 7 yr old)
• Rapid weight gain during first 4 months was
• associated with increased risk of being
• overweight(BMI gt 95th percentile) at 7 yr old
• independent of birth weight and weight at 1 yr
  old

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Cross-sectional growth rates in Pima Indian
children(from Lindsay et al. Pediatrics 109e33,
2002)
Weight
Weight-for-length
1.0
1.0
Girls
o
o
Boys
0.5
0.5
P lt0.001
Z score
o
o
Z score
0
0
o
o
-0.5
-0.5
1 2 4 6 9 12
1 2 4 6 9 12
Age (months)
Age (months)
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Environmental Factors First yearBreastfeeding
and Type 2 diabetes(from Pettit et al Lancet
350166,1997)
Rate of diabetes Adjusted for age and sex ()
Feeding groups
Odds Ratio for Breast v Bottle 0.41 (p 0.03)
Relative weight ()
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Importance of early interventions
Greater impact on the risk trajectories for
developing obesity and/or type 2 diabetes over
a lifetime ? lessens economic burden on
society
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Impact of environment ongenetic expression of
diabetes
In utero (LGA,SGA)
Childhood onset obesity
Disease threshold
Adult onset obesity
Genetic risk factor
negative factors accelerate expression
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Impact of environment contd
Genetic risk factor
positive factors delay expression
Exercise,diet-Adult
Exercise,diet Adult BF
Breastfed
Exercise,diet - Childhood
Exercise,diet Child BF
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Impact of environment- contd
In utero (LGA,SGA)
Genetic risk factor
Breastfeeding
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Significance of Metabolic Programming
A healthy pregnancy and breastfeeding appear to
have an impact on delaying the genetic
expression of Type 2 diabetes later in life
therefore
Womens health IS everyones health