KINESIOL 1Y03 Lecture Notes - Lecture 23: Impaired Glucose Tolerance, Dyslipidemia, Cytosine
22 Jun 2018
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Maternal-Foetal programming
Pregnancy
1st trimester = period of teratogenesis
2nd trimester = maximal foetal programming
3rd trimester = maximal foetal growth
Intra-uterine environment
Environmental influences begin in utero (maternal diet = nutrient supply)
Barker 1997 related foetal insult to later diabetes, CVD and BP (due to effects on kidneys)
nutritional insults at critical ontogenic stages leads to permanent epigenetic changes to
DNA alterations in chromatic remodeling and gene expression
Rat model of Intra-uterine development of diabetes
1) Pregnant rat has one uterine artery tied off utero-placental insufficiency
2) Child is SMA (small for gestation age), fed nutrient rish diet catches up 7 weeks
after birth
3) child then develops DM at 5-6months, and if gets pregnant = gains more weight /
becomes diabetic earlier
4) third generation have high BW, foetal hyperinsulinaemia (in utero), high beta-cell
mass at birth, then develop DM (reduced beta-cell mass + insulin resistance) and
downregulation of GLUT1 and GLUT4
Human model of Intra-uterine development of diabetes: Pima Indians
-= used to be successful arable farmers, were then moved to plantations by US
government with less work, and sugary/fatty diets provided
-children with DM mothers had higher adolescent incidence of serve obesity and
were more likely to develop T2DM
-The obesity was more severe in those with mothers that had DM before birth i.e.
experienced high glucose levels in utero = evidence for in utero effect
-50% of Pima Indian population now T2DM
Pederson hypothesis for effect of maternal hyperglycaemia during pregnancy
1) lots of glucose, no insulin crosses placenta
2) foetal pancreas stimulated at 14 weeks
3) foetal hyperinsulinaemia
4) foetal insulin resistance
Development of diabetes due to intra-uterine environment – thrifty gene hypothesis
- Low BW = low nutrition in pregnancy = glucose in muscle diverted to nervous system
- can confer advantages i.e. efficient metabolism leading to people who can
procreate on very restricted diets, but in a world of plenty this metabolic ‘efficiency’
1) obesity 2) insulin resistance due to less glucose reaching the pancreas in utero
- High BW = also increased risk of DM
Hence there is a U-shaped curve for the risk of DM
-T1DM, gestational DM and T2DM causes metabolic syndrome in the children due to
Intra-uterine growth promotion.
-Babies of T1DM / gestational DM mothers have 40% over the 90th percentile (c.f.
normal – 10%); T2DM mothers have over 50% over the 90th percentile. This is also
shown in children studied aged 6-8yo.
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Document Summary
Environmental influences begin in utero (maternal diet = nutrient supply) Barker 1997 related foetal insult to later diabetes, cvd and bp (due to effects on kidneys) Nutritional insults at critical ontogenic stages leads to permanent epigenetic changes to. Dna alterations in chromatic remodeling and gene expression. Human model of intra-uterine development of diabetes: pima indians. The obesity was more severe in those with mothers that had dm before birth i. e. experienced high glucose levels in utero = evidence for in utero effect. Pederson hypothesis for effect of maternal hyperglycaemia during pregnancy: lots of glucose, no insulin crosses placenta, foetal pancreas stimulated at 14 weeks, foetal hyperinsulinaemia, foetal insulin resistance. Development of diabetes due to intra-uterine environment thrifty gene hypothesis. Low bw = low nutrition in pregnancy = glucose in muscle diverted to nervous system. Can confer advantages i. e. efficient metabolism leading to people who can procreate on very restricted diets, but in a world of plenty this metabolic efficiency".
