Lecture 7: Developmental Origins of Metabolic Disease

Question 1

What is the leading cause of death in patients with diabetes?

Answer 1

CVD - 65% of people who died from CVD had some form of abnormal glucose metabolism

Question 2

What % of diabetic patients had hypertension?

Answer 2

70%

Question 3

How does diabetes lead to CVD?

Answer 3

Diabetes - elevated glucose levels damage cells within blood vessels, making them weaker, leading to CVD

Question 4

What characterises diabetes?

Answer 4

Chronic hyperglycaemia

Question 5

Why does diabetes occur?

Answer 5

Disrupted glucose homeostasis due to defects in insulin secretion or action

Question 6

How many people in Aus with Type 2 diabetes?

Answer 6

1.7 mil

Question 7

What is type 1 diabetes?

Answer 7

Type 1: intrinsic defect in insulin production, autoimmune, body cannot make insulin, early onset (

Question 8

What is type 2 diabetes?

Answer 8

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

Question 9

What structures does diabetes damage and what may this lead to?

Answer 9

Eyes, kidneys and blood vessels (damage to vessels can lead to lack of blood flow to tissues - amputations)

Question 10

What range do glucose levels stay at (healthy)?

Answer 10

~4-6.5 mmol/L

Question 11

Why does glucose level always need to remain at least at basal rate?

Answer 11

Brain is unable to synthesise glucose and so glucose needs to always be maintained at a basal rate, even when not eating

Question 12

Where is insulin released from?

Answer 12

Pancreatic beta cells in islets

Question 13

What is the secretion mechanism of insulin?

Answer 13

Biphasic

Question 14

What does insulin allow?

Answer 14

Uptake of glucose into cells via GLUT4

Question 15

What is normal glucose homeostasis?

Answer 15

Question 16

What is impaired glucose homeostasis?

Answer 16

Question 17

What is insulin resistance?

Answer 17

Condition where the body does not respond to insulin signals

Question 18

What is insulin sensitivity?

Answer 18

To what degree the body responds to insulin signals

Question 19

What are the mechanisms of low birth weight and diabetes?

Answer 19

-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

Question 20

Do genetic factors contribute to the IUGR diabetic phenotype?

Answer 20

No

Question 21

What is the thrifty phenotype?

Answer 21

• 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

Question 22

What is the insulin resistant concept?

Answer 22

1. 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

Question 23

What is the beta cell apoptosis concept?

Answer 23

1. 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

Question 24

What is the islet malformation concept?

Answer 24

1. 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

Question 25

What does uteroplacental insufficiency in the rat cause?

Answer 25

-Impaired glucose tolerance and diabetes in males (not females until pregnancy) -Mitochondrial dysfunction -Genetic and epigenetic changes

Question 26

What is gestational diabetes and what can it lead to?

Answer 26

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

Question 27

What are interventions for type 2 diabetes?

Answer 27

Improved diet, vitamin supplements, therapeutics/drugs, EXERCISE

Question 28

How does exercise affect diabetes?

Answer 28

Adult beta cells mass restored in growth restricted adult rats after 4 weeks of exercise