Diabetes type 1 Flashcards
What is diabetes
Group of metabolic disorders characteristed by hyperglycemia, disturbances in the metabolism of carbs, proteins and fats due to defects in insulin action or secretion or both.
Diabetes type 1 aetiology
-Unknown
-Dysfunctional HLA genes: help T cells recognize self antigens from non-self antigens
• When these do not work leads to autoimmune attacks on B cells
• Destruction of B cells- less insulin- more glucose in serum
• In type I- there is an autoimmune attack on islets- infiltration of Lymphocytes (Insulitis) and destruction of B cells
-Environmental triggers
• Chemicals
• Bacteria
• Viral: molecules on the surface of viral cells lead imitate molecules on the outside of B cells- MOLECULAR MIMICRY
How does diabetes increase the risk of macrovascular disease
One theory
- Glucose binds to LDL
- Prevents LDLs from binding to liver receptors
- LDLs cannot be taken up by liver
- LDLs stay in blood and lead to atherosclerosis
Second theory
- Arterioles are surrounded by an endothelial lining
- Endothelial lining makes up basal lining
- Between endothelial lining and the basal lining there is potential space that molecules can move into
- Around the basal laming there are smooth cells
- In DM: molecules (collagens and plasma proteins) move into the potential cell and then cannot move out- thickening of the basal lamina
How does diabetes lead to microvascular disease
Hyaline changes
- The narrowed vessels means less blood can flow through it
- Ischemia
- very damaging in kidneys, eyes, arterioles which supply nerves
Risk of morbity
- Amputation: x40
- End stage renal disease: X25
- Blindness: X25
how does diabetes lead to small vessel disease
- glucose added to proteins: glycosylation
- Initially reversible
- If strong covalent bonds form it is irreversible
How does glycosylation occur in small vessels
1-Collagen makes up basal lamina
- collagen does not usually bind to albumin
- when glucose present in the endothelial space, albumin binds to it
- albumin gets stuck in endothelial space
2-Cross-linked proteins
- usually basal lamina proteins do not cross link so can be removed easily
- Glycosylated proteins bind to their neighbouring proteins
- Cross linked proteins are difficult to remove
How does diabetes increase the risk of macrovascular disease
- Increases risk of Coronary HD 2-20x
- Increases risk of MI 2-5 x
- Increases risk of atherothrombotic stroke 2-3x
Who is most at risk of diabetes type 1
10-30 year olds
Hereditary links in diabetes type 1
- mother
- Father
- Identical twin
- Non-identical twin
- sibling
- Both parents
- If mother has Type 1: 1% risk
- If father has Type 1: 6% risk
- If sibling has Type 1: 8% risk
- If non-identical twin has Type 1: 10% risk
- If both parents have Type 1: 30% risk
- Monozygotic twins 30-50% concordance
Symptoms of diabetes type 1
- Thirst
- Tired
- Need to use toilet = Polyuria
- Weight loss
- Abdominal pain
what do you see on examination of patients with diabetes type 1
- Sweet breath due to ketone production
- May present with signs of infection e.g. tachycardia, RR
- Dehydration
- Minor infections e.g. thrush
Describe which genes are interfered with in autoimmune disruption in diabetes type 1
- Genes that modify immune function
- Genes that interfere with immune regulation
- Genes that influence beta-cell survival
What are the consequences of diabetes type 1
- Increased glucose production in the liver
- Reduced uptake of glucose in muscle cells
- Increased lipolysis in adipose cells
- Can lead to diabeteic Ketoacidosis
