Lecture 26: Treatment of Diabetes 1 Flashcards
define diabetes
metabolic disorder of multiple aetiology characterised by:
- chronic hyperglycaemia
- disturbances of carb, fat and protein metabolism
- defects in insulin secretion, insulin action or both
what 3 things would you look out for in a young patient suspected of diabetes (Type 1)
- polyuria
- polydipsia
- polyphagia
give the two main classifications of diabetes and describe them
Type 1
- insulin dependent
- pancreatic B cells destroyed so no insulin made
Type 2
- insulin resistant
- insulin stops working at target tissues ( muscle)
explain how a T2D patient might become insulin dependent
- insulin resistant
- pancreatic B cells produces excess insulin to try and overcome this
- B cells become exhausted and die
what molecule is measured when trying to measure insulin levels in plasma
C peptide
what are the types of diabetic complications that can occur
- microvascular e.g. retinopathy, nephropathy
- macrovascular e.g. atherosclerosis
- neuropathy
outline the differences between T1D and T2D
T1D:
- childhood/teen onset
- freq. malnourished
- 10-20% prevalence
- moderate genetic predisposition (epigenetic)
- B cell/insulin defect
T2D
- middle age onset
- freq. obese
- 80-90% prevalence
- very strong genetic predisposition
- insulin resistance or insulin insufficiency
how are insulin levels measured
C peptide ELISA
why is C peptide measured (not just insulin) to determine insulin levels in blood
- might measure inactive forms of insulin
- active form only consists of A chain and B chain
what stimulates insulin secretion
- metabolic signals e.g. blood glucose
- vagal stimulation
describe B cells release of insulin in phases
- biphasic pulsatile release into portal vein –> significant amount removed by first pass through liver
- rapid 1st phase triggered by ^ glucose levels
- slow sustained 2nd phase of newly formed vesicles triggered independently of glucose
- half life is 5-6mins
what would be seen in insulin secretion phases for T2D
no/insufficient 2nd phase
how is insulin released from B cells
- glucose enters B cells via GLUT 2
- glucose metabolism initiated by glucokinase (phosphorylation - liver and B cells only)
- ^ ATP and dec. in ADP
- alters/closes K-ATP channels
- B cell depolarises –> activation of voltage dependent Ca2+ influx
- ^ of intracellular Ca2+ triggers insulin secretion
how does insulin stimulate glucose uptake
- insuline binds to tyrosine kinase receptors
- signalling pathway stimulated
- triggers glucose uptake by GLUT 4 in liver muscle and fat cells
describe the metabolic effects of insulin on liver
- anabolic
- ^ glycolysis
- ^ glycogen synthesis
- dec. gluconeogenesis
- dec. glycogenolysis
describe effect of insulin on skeletal muscle
- ^ GLUT4 translocation
- ^ glycogen synthesis
- ^ glycolysis
- ^ a.a. uptake and prot synthesis
describe effect of insulin on fat cells
- ^ GLUT4 translocation
- ^ glycerol
- -> ^ synthesis of fatty acids and triglycerides
- -> inhibits lipolytic actions of adrenaline, GH and glucagon
outline some medical indications for insulin
- needed for Px w/ T1D
- emergency treatment of ketoacidosis
- improves control of diabetes in T2D and for intercurrent events e.g. surgery or infection
- during pregnancy
- emergency treatment of hyperkalaemia
how is insulin that is used for therapy treatments retrieved from
made as recombinant human protein in bacteria
why is oral administration of insulin not successful
- insulin is a peptide
- degraded by GIT
how is insulin most commonly administered
Subcutaneously
what effect does having different formulations of insulin have
rate of absorption delayed by ^ particle size
what are the 3 insulin formulations and how do they differ
short acting (pen)
- onset 30min
- short duration
intermediate acting
- 16-35hr onset
- longer half life
- insulin coupled w/ zinc
long acting
- > 35hr onset
- coupled w/ zinc
what is insulin glargine (Lantus) and why is it good
- modified insulin
- long acting
- provides constant basal insulin supply
- prolonged absorption from site of injection
- reduces risk of night time hypoglycaemia
what is the best therapy for T1D
mixture of short and medium lasting insulin injected before meals
- new strategy incl. long lasting insulin delivered by pump w/ short acting taken before meals
list some factors affecting subcutaneous absorption of insulin after self administration
- site of injection
- exercise = blood flow at site
- depth of injection
- conc. and dose of insulin
- insulin degrading activity in subcutaneous tissue
give some side effects of insulin therapy
- hypoglycaemia –> coma –> brain damage
(reversible with glucagon or sweet drinks) - allergic reactions
- lipodystrophy
- lipohypertrophy
how can insulin affect serum K+ levels
- stimulates K+ uptake into cells via activation of Na/K ATPase pump
- IV insulin can lead to dangerous reduction in serum K+
- diabetic ketoacidosis
explain how ketoacidosis occurs
- T1D Px doesn’t take insulin
- body shifts to start breaking down fat as source of energy
- prod. ketones and acids which lower blood pH
give some signs of diabetic ketoacidosis
- thirsty
- dehydrated
- fruity smelling breath
- ^ blood glucose
- drowsiness
- ^ HR
- vomiting
- weight loss
- frequent urination
treatment for DKA
give saline and IV insulin
