Lecture 26: Treatment of Diabetes 1

Question 1

define diabetes

Answer 1

metabolic disorder of multiple aetiology characterised by:

• chronic hyperglycaemia
• disturbances of carb, fat and protein metabolism
• defects in insulin secretion, insulin action or both

Question 2

what 3 things would you look out for in a young patient suspected of diabetes (Type 1)

Answer 2

• polyuria
• polydipsia
• polyphagia

Question 3

give the two main classifications of diabetes and describe them

Answer 3

Type 1

• insulin dependent
• pancreatic B cells destroyed so no insulin made

Type 2

• insulin resistant
• insulin stops working at target tissues ( muscle)

Question 4

explain how a T2D patient might become insulin dependent

Answer 4

• insulin resistant
• pancreatic B cells produces excess insulin to try and overcome this
• B cells become exhausted and die

Question 5

what molecule is measured when trying to measure insulin levels in plasma

Answer 5

C peptide

Question 6

what are the types of diabetic complications that can occur

Answer 6

• microvascular e.g. retinopathy, nephropathy
• macrovascular e.g. atherosclerosis
• neuropathy

Question 7

outline the differences between T1D and T2D

Answer 7

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

Question 8

how are insulin levels measured

Answer 8

C peptide ELISA

Question 9

why is C peptide measured (not just insulin) to determine insulin levels in blood

Answer 9

• might measure inactive forms of insulin

- active form only consists of A chain and B chain

Question 10

what stimulates insulin secretion

Answer 10

• metabolic signals e.g. blood glucose

- vagal stimulation

Question 11

describe B cells release of insulin in phases

Answer 11

• 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

Question 12

what would be seen in insulin secretion phases for T2D

Answer 12

no/insufficient 2nd phase

Question 13

how is insulin released from B cells

Answer 13

• 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

Question 14

how does insulin stimulate glucose uptake

Answer 14

• insuline binds to tyrosine kinase receptors
• signalling pathway stimulated
• triggers glucose uptake by GLUT 4 in liver muscle and fat cells

Question 15

describe the metabolic effects of insulin on liver

Answer 15

• anabolic
• ^ glycolysis
• ^ glycogen synthesis
• dec. gluconeogenesis
• dec. glycogenolysis

Question 16

describe effect of insulin on skeletal muscle

Answer 16

• ^ GLUT4 translocation
• ^ glycogen synthesis
• ^ glycolysis
• ^ a.a. uptake and prot synthesis

Question 17

describe effect of insulin on fat cells

Answer 17

• ^ GLUT4 translocation
• ^ glycerol
• -> ^ synthesis of fatty acids and triglycerides
• -> inhibits lipolytic actions of adrenaline, GH and glucagon

Question 18

outline some medical indications for insulin

Answer 18

• 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

Question 19

how is insulin that is used for therapy treatments retrieved from

Answer 19

made as recombinant human protein in bacteria

Question 20

why is oral administration of insulin not successful

Answer 20

• insulin is a peptide

- degraded by GIT

Question 21

how is insulin most commonly administered

Answer 21

Subcutaneously

Question 22

what effect does having different formulations of insulin have

Answer 22

rate of absorption delayed by ^ particle size

Question 23

what are the 3 insulin formulations and how do they differ

Answer 23

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

Question 24

what is insulin glargine (Lantus) and why is it good

Answer 24

• modified insulin
• long acting
• provides constant basal insulin supply
• prolonged absorption from site of injection
• reduces risk of night time hypoglycaemia

Question 25

what is the best therapy for T1D

Answer 25

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

Question 26

list some factors affecting subcutaneous absorption of insulin after self administration

Answer 26

• site of injection
• exercise = blood flow at site
• depth of injection
• conc. and dose of insulin
• insulin degrading activity in subcutaneous tissue

Question 27

give some side effects of insulin therapy

Answer 27

• hypoglycaemia –> coma –> brain damage
  (reversible with glucagon or sweet drinks)
• allergic reactions
• lipodystrophy
• lipohypertrophy

Question 28

how can insulin affect serum K+ levels

Answer 28

• stimulates K+ uptake into cells via activation of Na/K ATPase pump
• IV insulin can lead to dangerous reduction in serum K+
• diabetic ketoacidosis

Question 29

explain how ketoacidosis occurs

Answer 29

• 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

Question 30

give some signs of diabetic ketoacidosis

Answer 30

• thirsty
• dehydrated
• fruity smelling breath
• ^ blood glucose
• drowsiness
• ^ HR
• vomiting
• weight loss
• frequent urination

Question 31

treatment for DKA

Answer 31

give saline and IV insulin