Lecture 7: Developmental Origins of Metabolic Disease Flashcards
What is the leading cause of death in patients with diabetes?
CVD - 65% of people who died from CVD had some form of abnormal glucose metabolism
What % of diabetic patients had hypertension?
70%
How does diabetes lead to CVD?
Diabetes - elevated glucose levels damage cells within blood vessels, making them weaker, leading to CVD
What characterises diabetes?
Chronic hyperglycaemia
Why does diabetes occur?
Disrupted glucose homeostasis due to defects in insulin secretion or action
How many people in Aus with Type 2 diabetes?
1.7 mil
What is type 1 diabetes?
Type 1: intrinsic defect in insulin production, autoimmune, body cannot make insulin, early onset (
What is type 2 diabetes?
Type 2: insulin resistance, body produces insulin but cannot respond to it, usually late onset (bad diet and lifestyle factors), 85-90% of Australian diabetes
What structures does diabetes damage and what may this lead to?
Eyes, kidneys and blood vessels (damage to vessels can lead to lack of blood flow to tissues - amputations)
What range do glucose levels stay at (healthy)?
~4-6.5 mmol/L
Why does glucose level always need to remain at least at basal rate?
Brain is unable to synthesise glucose and so glucose needs to always be maintained at a basal rate, even when not eating
Where is insulin released from?
Pancreatic beta cells in islets
What is the secretion mechanism of insulin?
Biphasic
What does insulin allow?
Uptake of glucose into cells via GLUT4
What is normal glucose homeostasis?
What is impaired glucose homeostasis?
What is insulin resistance?
Condition where the body does not respond to insulin signals
What is insulin sensitivity?
To what degree the body responds to insulin signals
What are the mechanisms of low birth weight and diabetes?
-Reduced beta cell mass and insulin secretion -Reduced glucose uptake and increased glucose production -Reduced insulin sensitivity -Reduced insulin inhibition of lipolysis -Reduced pancreatic function
Do genetic factors contribute to the IUGR diabetic phenotype?
No
What is the thrifty phenotype?
- Fetus can adapt to suboptimal intrauterine conditions and restrict nutrient supply to most vital organs - Events during critical periods may permanently program the fetus metabolism to enhance survival (expecting a poor postnatal environment) - If postnatal nutrition is abundant then the advantages are lost – developmental mismatch can lead to harmful long term effects
What is the insulin resistant concept?
- Body less sensitive to insulin with age 2. Beta cells compensate – increase insulin secretion 3. Beta cells exhausted – apoptosis and reduced insulin 4. Sustained IFG 5. Further decline 6. Type 2 diabetes
What is the beta cell apoptosis concept?
- Beta cell apoptosis – spontaneous 2. Remaining beta cells compensate – increase insulin secretion 3. Beta cells exhausted – apoptosis and reduced insulin 4. Sustained IFG 5. Further decline 6. Type 2 diabetes
What is the islet malformation concept?
- Intrinsic beta cell deficit 2. Remaining beta cells compensate – increase insulin secretion 3. Age related insulin resistance 4. Sustained IFG 5. Increase in insulin resistance and inability to compensate 6. Type 2 diabetes
What does uteroplacental insufficiency in the rat cause?
-Impaired glucose tolerance and diabetes in males (not females until pregnancy) -Mitochondrial dysfunction -Genetic and epigenetic changes
What is gestational diabetes and what can it lead to?
Occurs during pregnancy when body cannot cope with extra demand for insulin. Can lead to increased risk of diabetes in offspring and increase in lifetime risk of diabetes in mother
What are interventions for type 2 diabetes?
Improved diet, vitamin supplements, therapeutics/drugs, EXERCISE
How does exercise affect diabetes?
Adult beta cells mass restored in growth restricted adult rats after 4 weeks of exercise
