Diabetes Mellitus

Question 1

Type 1

Answer 1

• immune reaction against our beta cells
• decrease in beta cells leads to decrease in plasma insulin
• responsive cells increase receptor number
• if untreated leads to ketoacidosis, coma
• autoimmunity emphasised by-
  Helper T and cytotoxic T cells in islets- cell mediated response.
  Circulating islet cell antibodies
  10-20% develop other autoimmune diseases
  Concordance rate is lower than 50% indicating environmental factors

Question 2

Normal glucose metabolism

Answer 2

• increase in plasma glucose
• increase in insulin release from beta cells of islets of langherans
  Insulin required for:
• transport of glucose and amino acids into cells
• glycogen formation (liver and muscle)
• triglyceride formation from glucose
• protein synthesis
• nucleic acid synthesis
  Therefore if not enough glucose in cells, these processes reverse

Question 3

Type 2

Answer 3

More common
Multiple gene defects
No HLA linkage
No autoimmunity
Concordance rate >50% due to genetics
Main metabolic defect: insulin resistance
- problems with post receptor signalling
- decrease no receptors?
- increased FFA’s, increased resistin, decrease adiponectin, others?
- with time, amylin deposition, amyloidosis, islet fibrosis, decreased beta cell mass
- plasmid insulin levels initially normal to high

Question 4

Untreated or poorly treated diabetes

Answer 4

Insulin deficiency type 1, insulin resistance type 2

• hyperglycaemia -> polyphagia
• glycosuria
• plyuria
• volume depletion -> polydipsia
• diabetic coma

Insulin deficiency type 1

• increased lipolysis
• increased plasma free fatty acids
• increased hepatic FFA oxidation
• increased ketone bodies
• ketoacidosis
• diabetic coma

Question 5

Type 1 and 2 complications: hyperglycaemia- non enzymatic glycosylation

Answer 5

Increase in blood glucose in the blood.

• non enzymatic, glycosylation is adding glucose to peitein.
• glucose can stick to protein without enzyme when there is an abundance- abnormal. Include albumin, collagen, LDLs and most proteins.
• cannot allow remodelling to occur and changes other structures and functions
• cross linkage occurs between proteins, unable to break down and can cause atherosclerosis eg. Accumulation of LDLs in arteries, glucose attached to LDL’s forming these cross linkages- causes atherosclerosis

Question 6

Type 1 and 2 complications: hyperglycaemia: excess intercellular glucose

Answer 6

• nerves, lens, kidneys and blood vessels do not require insulin to allow glucose to enter- problematic.
• extra cellular glucose - sorbitol and fructose- increase intercellular osmolarity- increase in water- cell injury (swelling) eg. Schwann cells, axons (neuropathy), cataracts

Question 7

Type 1 and 2 complications: hyperglycaemia: Basement membrane thickening

Answer 7

• hyperglycaemia stimulates production of more basement membrane
• poor perfusion. Membrane becomes leaky to fluid and proteins (microangiopathy)
• increased glucose in interstitial fluid

Question 8

Type 1 and 2 complications: hyperglycaemia: vascular system

Answer 8

- atherosclerosis - myocardial infarction, stroke, gangrene 
Risk factors: 
High LDLs 
Decreased HDLs
Hypertension 
Increased platelet adhesiveness

Question 9

Type 1 and 2 complications: hyperglycaemia: nervous system

Answer 9

• peripheral, symmetric
• sensory (proprioception, touch, pressure, pain), autonomic (dilation of arterioles, poor circulation, heat, results in poor peripheral perfusion in capillaries, incontinence) and lower motor.
• due to direct damage or less commonly microangiopathy

Skin has increased risk of infections and ulcers due to poor perfusion of blood. More glucose than normal (hypoxic). Bacterial loving environment. Impaired body defences, white blood cells do not work as well.