Lecture 5: Influence of in Utero Malnutrition on Disease in Adult Life

Question 1

What are the major non-communicable diseases (lifestyle diseases)

Answer 1

• Cardiovascular Disease
• Metabolic diseases (obesity, type 2 DM and fatty liver)
• Sarcopenia
• Osteoporosis
• Respiratory Diseases
• Cancers
• Cognitive decline and dementia

Question 2

What are the top three global annual deaths?

Answer 2

1. Cardiovascular diseases and Communicable diseases, maternal and peritenal condition and nutritional deficiencies.
2. Cancer
3. Injuries

Question 3

WHO projects a global increased of _______% in some non-communicable diseases over the next decade

Answer 3

17%

Question 4

In 2008, an estimate ____ million of the _____ million global deaths were due to non-communicable diseases and that nearly ____% of those deaths occurred in developing countries

Answer 4

36 million of the 57 million

nearly 80%

Question 5

Maternal and child health is inextricably linked with what?

Answer 5

Non-communicable diseases and their risk factors, specifically as prenatal malnutrition and low birth weight create a predisposition to obesity, high blood pressure, heart disease and diabetes later in life.
Pregnancy conditions, such as maternal obesity and gestational diabetes, are associated with similar risks in both the mother and her offspring.

Question 6

what adulthood disease is birthweight associated with

Answer 6

low birthweight = higher CHD mortality, higher percent metabolic syndrome, higher prevalence of type 2 diabetes mellitus

Question 7

Women exposed to famine (less then 700kcal/day) in early pregnancy had babies with increased _____ in adulthood?

Answer 7

HTN

babies usually of normal weight

Question 8

Women exposed to famine (less then 700kcal/day) in late pregnancy had smaller babies who developed _____ and ____ ______ in adulthood

Answer 8

obesity and glucose intolerance

Question 9

What is the Barker Hypothesis “fetal origins of adult disease”

Answer 9

Poor Nutrient exposure in early life (fetus, infant, early childhood) leads to Permanent change in structure and function of tissues and organs leads to Poor ability to cope with later environment means increased risk of disease in adulthood

Question 10

What are the factors that lead to perturbed maternal-fetal environment?

Answer 10

Inadequate Placental Supply 
Nutrient Restriction 
Hormonal Abnormalities 
Gestational Diabetes 
Maternal Obesity

Question 11

How does skeletal muscle, brain ,kidney, pancreas and adipose tissue adapt to this perturbed intrauterine environment?

Answer 11

Skeletal muscle: decreased muscle mass, decreased insulin sensitivity, and increased lipid oxidation
Brain: altered neuronal development, leptin resistance and lipid accumulation
Kidney: decreased nephrogenesis and altered renin-angiotensin system activities
Pancreas: decreased Beta-cell mass, decreased insulin secretion
Adipose tissue: decreased insulin-stimulated glucose uptake, increased fat storage and endoplasmic reticulum stress

Question 12

All the adaptions of the various organs to the perturbed intrauterine environment can lead to what diseases?

Answer 12

Impaired glucose tolerance
Insulin resistance
Type 2 diabetes mellitus
Metabolic syndrome

Question 13

What was the BMI in 2 year old children who were breast fed, lower and higher protein content formula?

Answer 13

Higher protein formula (largest BMI)
Breast Fed
Lower protein formula (lowest BMI)

Question 14

Obesity/Visceral obesity, Metabolic syndrome, Diabetes, HTN, CHD and Asthma in adulthood, link to what factors in utero and early life?

Answer 14

1. Genes and Environment
2. Fetal over-nutrition (maternal obesity, high pregnancy weight gain, diet in pregnancy, gestational DM)
3. Postnatal nutrition and growth (lack or short BF, over feeding or excessive protein intake)
4. Fetal undernurtrition and low birth weight (maternal imbalances and placental dysfunction)

Question 15

A poor start to life is associated with effects on structure and function of a range of organs and control systems in the offspring. What are these organs and control systems?

Answer 15

Fat 
Muscle 
Bone 
CHD, respiratory and renal systems
Mood and Behavior 
Stress responses 
Cognitive function 
Timing of puberty, reproductive function 
Immune responses 
(these effects can be subtle, so they dont immediately signal danger. But they have lifelong effects. They do not cause NCDs but they alter how a person responses to their lifestyle later, and so their risk of NCDs)

Question 16

Earlier intervention in chronic non communicable diseases in mothers and infants improves what?

Answer 16

Improves functional capacity and responses to new challenges

Question 17

Late intervention or no intervention in adulthood in chronic non communicable diseases impacts who?

Answer 17

Late intervention impactful for vulnerable groups

Question 18

From a study done in Finland, adults who had CHD, showed what trends in height, BMI and weight in early life?

Answer 18

Height, BMI and Weight were all decreased from 0months until about 10 years of age.
At about 10 years of age the height weight and BMI drastically started increasing
(girls tend was sooner in age then boys, because girls tend to hit puberty faster)
—therefore this shows that small size in birth followed by rapid catch up later on may increase disease risk

Question 19

Overweight/obese child and overweight/obese adult shows an increased relative risk for what diseases?

Answer 19

Type 2 Diabetes (childhood and adult fatness both play a role)
HTN
High risk LDL
High risk HDL
High risk triglycerides
High risk carotid artery intima media thickness

Question 20

What body size factors play a role in later disease risk?

Answer 20

1. Small birth weight/size
2. Large birth weight/size
3. Small birth size and later rapid catchup (to excess)
4. Childhood obesity
5. Adult obesity
6. Combination of childhood and adult obesity

Question 21

Epigenetics is the mechanism that plays a role in the body size factors and later disease risk. What is epigenetics?

Answer 21

• –Refers to stable changes in DNA structure (not changes in base sequence though) and modified gene expression
• –carried between generations

Question 22

Another mechanism that plays a role in the body size factors and later disease risk is differential methylation. Explain what differential methylation is and what the mechanism is.

Answer 22

Differential methylation of individual CpGs induces graded regulation of transcription

• –cytosine is methylated to 5-methyl cytosine
• –the majority of methylated cytosine is found as a dinucleotide CpG
• -CpGs are not randomly distributed throughout the genome but are clustered at the 5’ ends of genes (CpG islands)
• -Methylated promoter is now unable to do transcription and then eventually translation to proteins

Question 23

A study done on rats showed the correlation between maternal diet and methylation of promoter region of gene and gene expression. What were these results?

Answer 23

In the control group: there was increased DNA methylation of promoter region and therefore decreased mRNA concentration (again due to lack of the ability to perform transcription)
In Low Protein dietary group: decreased DNA methylation and increased mRNA concentration
(notice the correlation between this methylation of the promoter group and mRNA concentration)
–note done with hepatic glucocorticoid receptor

Question 24

The rat study showed what results?

Answer 24

Low protein diet induces, and folic acid prevents altered epigenetic regulation that in turn affects metabolism

Question 25

In a women a poor education attainment, poor diet, less exercise and obesity leads to what in pregnancy, infantile life and childhood life and adult life?

Answer 25

Pregnancy: minimal changes in diet and health behaviors
Infant: poor birth outcome (small or large baby); poor infant diet
Childhood: greater fat mass, less lean mass and lower IQ
Adulthood: poorer educational attainment

Question 26

order of decreasing risks of type 2 diabetes according to child and adult weight

Answer 26

most risk: ow/obese as a child and adult
normal weight as child but obese as an adult
obese as child but normal weight as as adult
least risk: normal weight as child and an adult