Diabetes Flashcards
Staging of diabetes
Type 1
Can be found with HLA makers and auto-antibodies without abnormality for a while before developing impairment of glucose tolerance then proceeding into complete insulin dependence
Type 2
Insulin production begins to fail and begin to have a low glucose tolerance. Initially lifestyle changes, the tablets then insulin
How many diabetics in the uk
2.6 million in 2009 and undiagnosed million
15 in 100000 type 1
2% pop type 2
Why is persistent hyperglycaemia harmful to peripheral tissues and what enzyme does It affect
Some peripheral nerves like the eye and kidney don’t need insulin to uptake glucose, but based on extracellular glucose conc.
Affects, and depletes NADPH
- as intracellular gluc conc increases, the enzyme aldose reductase metabolises the glucose ( glucose + NADPH + H+ = sorbitol + NADP+)
What is HbA1c
Glucose binds to the terminal valine of haemoglobin forming HbA1c and as RBC lasts 3 months, the percentage of HbA1c is good indication of average glucose concentration over 3 months.
Normal is 5%
Poorly controlled is 10%+
What are the clinical complications
Micro vascular
- stroke
- MI
- poor circulation
Macro vascular
- retinopathy
- nephroapathy
- neuropathy
- gangrenous limbs - feet
What performs endocrine function in pancreas
About a million Islets of langerhans (0.25 mm and ~6000 cells)
- contains beta cells (70%) which makes insulin
- contains alpha cells (20%) which makes glucagon
Treatment of type 2
Lifestyle and diet Insulin Non insulin - biguandies - thiazolidinediones - GLP1 analogues
How is insulin stored and transported
Stored in beta cell granules as crystalline zinc insulin complex. When released, it dissolves in the plasma and circulates as a free hormone - not bound to protein
What are the target tissues of insulin
Major targets are liver, skeletal muscle and adipose tissue.
Insulin is required for the normal growth and development of most other tissues
What are the main actions of insulin
Major actions on metabolism of carbs, lipids and amino acids
- increased glucose o adipose and sk muscle
- increased glycogenesis decreased glycogenolysis in liver and muscle
- decreased gluconeogensis in liver
- increased glycolysis in liver and adipose
- decreased lipolysis in adipose
- increase esterification of fatty acids
- decreased keto genesis in liver
- decrease proteolysis in liver, sk muscle and heart muscle
How is insulin controlled
Metabolites
- glucose, amino acids, fatty acids
GI tract
- gastrin, secretin, cholecystokinin
Neurotransmitters
- adrenaline, noradrenaline, acetylcholine
What is the structure and synthesis
Single polypeptide hormone without disulphide bridges but 3D structure that takes active conformation whe n binding to target site
Synthesis by larger precursor (pre-pro glucagon)
What are the four main actions of glucagon
- increase glycogenolysis and decrease glycogenesis in liver
- increase gluconeogenesis in liver
- increase ketogenesis in liver
- increase lipolysis in adipose
What is the MOA of glucagon
Glucagon binds to G protein coupled receptors (GPR)
Bind activates adenylate cyclase which increase cAMP
High levels of cAMP activates protein kinase A (PKA)
PKA phosphorylates target cells
Clinical separators of type 1 and type 2
Type 1 Commonest type in young people Progressive loss of pancreatic beta cells Rapidly fatal if untreated Treated with insulin
Type 2
90% suffers - mainly older
May be present for long time before diagnosis
May not immediate treatment, but eventually does
Progressive loss of beta cells but disorders of insulin secretion and tissue sensitivity
