Flashcards in Lecture 5: Influence of in Utero Malnutrition on Disease in Adult Life Deck (26)
What are the major non-communicable diseases (lifestyle diseases)
*Metabolic diseases (obesity, type 2 DM and fatty liver)
*Cognitive decline and dementia
What are the top three global annual deaths?
1. Cardiovascular diseases and Communicable diseases, maternal and peritenal condition and nutritional deficiencies.
WHO projects a global increased of _______% in some non-communicable diseases over the next decade
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
36 million of the 57 million
Maternal and child health is inextricably linked with what?
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.
what adulthood disease is birthweight associated with
low birthweight = higher CHD mortality, higher percent metabolic syndrome, higher prevalence of type 2 diabetes mellitus
Women exposed to famine (less then 700kcal/day) in early pregnancy had babies with increased _____ in adulthood?
(babies usually of normal weight)
Women exposed to famine (less then 700kcal/day) in late pregnancy had smaller babies who developed _____ and ____ ______ in adulthood
obesity and glucose intolerance
What is the Barker Hypothesis "fetal origins of adult disease"
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
What are the factors that lead to perturbed maternal-fetal environment?
Inadequate Placental Supply
How does skeletal muscle, brain ,kidney, pancreas and adipose tissue adapt to this perturbed intrauterine environment?
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
All the adaptions of the various organs to the perturbed intrauterine environment can lead to what diseases?
Impaired glucose tolerance
Type 2 diabetes mellitus
What was the BMI in 2 year old children who were breast fed, lower and higher protein content formula?
Higher protein formula (largest BMI)
Lower protein formula (lowest BMI)
Obesity/Visceral obesity, Metabolic syndrome, Diabetes, HTN, CHD and Asthma in adulthood, link to what factors in utero and early life?
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)
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?
CHD, respiratory and renal systems
Mood and Behavior
Timing of puberty, reproductive function
(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)
Earlier intervention in chronic non communicable diseases in mothers and infants improves what?
Improves functional capacity and responses to new challenges
Late intervention or no intervention in adulthood in chronic non communicable diseases impacts who?
Late intervention impactful for vulnerable groups
From a study done in Finland, adults who had CHD, showed what trends in height, BMI and weight in early life?
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
Overweight/obese child and overweight/obese adult shows an increased relative risk for what diseases?
Type 2 Diabetes (childhood and adult fatness both play a role)
High risk LDL
High risk HDL
High risk triglycerides
High risk carotid artery intima media thickness
What body size factors play a role in later disease risk?
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
Epigenetics is the mechanism that plays a role in the body size factors and later disease risk. What is epigenetics?
---Refers to stable changes in DNA structure (not changes in base sequence though) and modified gene expression
---carried between generations
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.
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
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?
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
The rat study showed what results?
Low protein diet induces, and folic acid prevents altered epigenetic regulation that in turn affects metabolism
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?
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