Theme C lecture 7 Flashcards
What is the leading cause of death in patients with known/unknown diabetes?
Cardiovascular disease
*Many people with diabetes don’t know they have it
What percentage of diabetics have hypertension?
70%
Why does diabetes contribute to cardiovascular disease?
Elevated blood glucose damages endothelial cells. This results in weakened blood vessels and in turn cardiovascular disease.
What causes diabetes, generally speaking?
Defects in insulin secretion, action, or both.
How many people in the world suffer from diabetes?
366 million people globally.
How many people suffer from diabetes in Australia?
2.5 - 3 million in Australia
Interesting fact:
half the people with diabetes don’t even know they have it
What are the types of complications that can arise from diabetes?
Microvascular: retinopathy and nephropathy
Macrovascular:
Heart disease and stroke.
Why is it important for glucose levels to be maintained?
Glucose levels should be maintained in the blood to constantly supply the brain.
How does insulin get produced?
biphasic secretion. It allows entry of glucose into the cell by upregulating GLUT.
It also suppresses liver glucose production.
What stimulate change in beta cell mass?
beta cell mass changes in response to demand
How does insulin regulate glucose levels in the blood?
1) Increase in blood glucose.
2) Increase in insulin secretion
3) Glucose is utilised by muscle, liver, adipose tissue, etc
4) Blood glucose decreases
5) negative feedback reduces insulin secretion
What is the difference between insulin resistance and sensitivity?
Insulin resistance is a condition where the body does not respond to insulin signals
Insulin sensitivity is the degree to which the body responds to insulin.
The less sensitive an individual is to insulin the more resistant he is.
What are some risk factors for diabetes?
Diet
Lifestyle
Low birth weight
What did monozygotic twin experiments show about the nature of insulin resistance?
Between 2 twins the one with lowest birth weight have an increased insulin secretion and higher blood sugar levels.
What period during gestation is most important in programming of metabolic dysfunction?
Developmental insults during late gestation may be a critical period in programming metabolic dysfunction.
What is the “thrifty phenotype” hypothesis?
Fetus can adapt to suboptimal intrauterine conditions by redirecting nutrients to most vital organs (brain) at expense of other organs.
Events during critical periods may permanently program the fetus metabolism to enhance survival.
If postnatal nutrition is abundant, advantage is lost.
What is the result of IUGR malnutrition?
Increase in malnutrition:
Decreases beta cell mass
Decrease in glucose uptake and increases glucose production
Decrease in insulin sensitivity
Inhibition of lipolysis
All these factors result in a decrease in pancreatic function and glucose intolerance and insulin and resistance and in turn diabetes
What happens to insulin sensitivity during aging?
It decreases
What are the steps in type 2 diabetes development?
1) Body less sensitive to insulin
2) beta cells compensate by increasing insulin secretion
3) Beta cells get exhausted and undergo more apoptosis causing decrease in insulin secretion
4) Sustained IFG
5) Further decline
6) Sustained type 2 diabetes
How do pancreatic beta cells respond to increased insulin resistance?
Pancreatic beta cells increase insulin secretion in response to decline in insulin sensitivity until a point of beta cell exhaustion
What does fetal programming do to the pancreas?
It decreases beta cell mass at birth. For this reason the exhaustion point is lower for the beta cells of these individuals
Why is uteroplacental insufficiency the most commonly used method during research of fetal programming?
uteroplacental insufficiency is most commonly used in experiments because it is the leading cause of low birth weight in western countries
How do the genders differ in glucose tolerance?
the fetal programming effect of glucose tolerance happens more often in males than females.
If the growth restricted females become pregnant they have impacted glucose tolerance during pregnancy.
What was seen in IUGR and metabolic dysfunction rats?
Structurally:
Decrease in pancreas and muscle mass
Decrease in islet and beta cell mass by 70%
Decrease in pancreatic vascularisation
Molecular changes:
Gene and protein expression (receptors, growth, and transcription factors.)
Mitochondrial dysfunction (ATP is critical-insulin production and release.
Epigenetic changes
What is gestational diabetes?
Occurs during pregnancy when body can not cope with extra demands for insulin.
What does gestational diabetes do to offspring?
Increases risk of diabetes in offspring.
Increases lifetime risk of diabetes in the mother.
Gestational diabetes can influence several generations in a row
What are some interventions that can decrease the risk associated with gestational diabetes?
Improved diet
Vitamin supplements
Therapeutics/Drugs
Exercise/physical activity
How does exercise help decrease the risk caused by gestational diabetes?
It increases beta cell mass restored in growth restricted adult rats.
