L11.1 Developmental origins of metabolic diseases Flashcards
1
Q
Relationship of diabetes and CVD
A
- CVD is the leading cause of death in patients with diabetes
- 70% of diabetic patients have hypertension
2
Q
How does diabetes lead to CVD
A
- Due to BV damage from elevated blood glucose
3
Q
Type 1 diabetes
A
- Insulin dependent (defective insulin production)
- Early onset, 10-15% cases
4
Q
Type 2 diabetes
A
- Non-insulin dependent
- Insulin resistance
- Late onset, but recently ↑ in children (due to bad diet and lifestyle factors)
5
Q
Why don’t many people realise they have diabetes?
A
- Symptoms don’t manifest at early stages and blood glucose has been elevated
- Leads to Complications:
- Microvascular
- Damage to BV: Retinopathy/nephropathy
- BV don’t supply to periphery → tissues can’t regenerate and need to be amputated
- Damage to BV: Retinopathy/nephropathy
- Macrovascular
- Heart diseases/stroke…
- Microvascular
6
Q
Secretion of insulin
A
- Secreted by β-cells in islet cells in pancreas
- β-cell mass is dynamic → changes according to demand
- Biphasic secretion
7
Q
Insulin
A
- Allows uptake of glucose into cells (via GLUT4)
- Suppress liver glucose production
- Glucose homeostasis
8
Q
Glucose homeostasis
A
- Food → causes spike in glucose
- Body maintains strict glucose range (~4-~6.5mmol/L)
- Brain is unable to syn/store glucose → constant supply is needed
- Insulin is closely mirrored by glucose → ↑glucose → ↑insulin to ↓glucose
- -ve FB from ↓glucose to inhibit further insulin secretion
9
Q
Impaired glucose homeostasis
A
- Not secreting insulin/insulin resistance
- Impairment leads to hyperglycaemia and diabetes
- Impaired glucose tolerance does not equal diabetes
10
Q
Insulin sensitivity vs resistance
A
- Resistance → body does not respond to insulin signals
- Sensitivity → how responsive the body is to insulin signals
11
Q
Low birth weight associated with metabolic dysfunction
A
- Hyperinsulinaemic → suggesting insulin resistance
- β-cells overcompensate to maintain normal glucose levels
- Genetic factors not contributing to the phenotype
- Intra-uterine condition is what is programming it
12
Q
When is the critical period for programming of metabolic dysfunction
A
- Developmental insults during late gestation may be a critical period for programming of metabolic dysfunction
13
Q
Thrifty phenotype hypothesis
A
- Fetus can adapt to suboptimal intrauterine conditions
- Limited nutritional supply → able to redirect nutrients to important organs like brain at the expense of other organs (pancreas/kidneys)
- Such events during critical periods → permanently program fetus metabolism to enhance survival in poor nutrition env (even postnatally)
- Programs itself to a deficient env post-natally as well → if postnatal nutrition is abundant → advantageous adaptation may be lost and may have harmful long-term consequences
14
Q
Mechanisms of low birth weight and diabetes
A
IUGR/malnutrition/GC leads to:
- ↓β-cell mass & secretion
- ↓glucse uptake/production in liver
- ↓insulin sensitivity in muscles
- ↓insulin inhibition of lipolysis in adipose tissue
- All leads to type 2 diabetes
15
Q
Insulin resistant concept
A
- Body less sensitive to insulin
- β-cells compensate ↑insulin secretion
- β-cells exhausted (↑apoptosis) → ↓insulin secretion
- Sustained impaired fasting glucose (IFG)
- Further ↓insulin sensitivity, secretion, β-cells
- Sustained type 2 diabetes
16
Q
B-cell apoptosis concept
A
- Βcells apoptosis → remaining βcells compensate → exhaust → IFG
17
Q
Islet malformation concept
A
- Most commonly seen in people born small
- Βcell deficient → compensate → insulin resistance with age → sustained IFG
