Diabetes and Drug Management

Question 1

What is the function of insulin?

Answer 1

To control blood glucose by moving glucose out of the blood stream into tissues mainly hepatocytes and muscles first then adipose tissue

Promotes protein synthesis and regulates metabolism in muscle cells

Inhibits the breakdown of fats

Question 2

Where is insulin produced

Answer 2

In the B cells in the Islet’s of Langerhans located in the pancreas

Question 3

Outline insulin synthesis

Answer 3

Precursor molecule produced form a single gene (proinsulin)

proinsulin cleaved into a and B chains linked by a disulphide bridge

further cleavage to produce active insulin a peptide hormone as well as a C polypeptide (no known function is excreted in the urine)

Question 4

How can urine testing be done to diagnose diabetes

Answer 4

isn’t the best test and isn’t sensitive enough or specific

any glucose present in the urine should be investigated further as it could be an indication of diabetes

Question 5

What is the random blood glucose level test?

Answer 5

Blood glucose taken 1/2 hour after last meal should be below 11.1 mmol/L for a health individual is above or equal to in diabetics

Question 6

What is the fasting blood glucose test?

Answer 6

Patient is starved for 8 hours only water

should be less than 5.5 mmol/L for a healthy person diabetics will be greater or equal to 7.0 mmol/L

Question 7

What is the HBA1c test?
Why is it so good?
What levels indicate diabetes?
When can you diagnose someone with diabetes?

Answer 7

measure glycated haemoglobin levels in the blood giving average blood glucose level over the past 10wks

over 48mmol/mol indicated diabetes
42 mmol/mol indicated pre-diabetes

If the test is over 48 mmol/mol and they have symptoms you can diagnose as diabetic
if they don’t have diabetes another test must be done

Question 8

What is type I diabetes

Answer 8

Absolute insulin deficiency no insulin is being produced due to an autoimmune disease destroying B cells in the pancreas

Question 9

Typical characteristics of type I

Answer 9

Can occur at any age

typically found in children

People tend to be normal weight slim

onset is usually dramatic

family history is less common

Question 10

What are the main symptoms of type I diabetes?

Answer 10

tiredness
weight loss
more frequent infections
polyuria
polydipsia
blurred vision
hyperglycaemic coma

Question 11

What are the main clinical presentations indicating type I

Answer 11

Presence of ketones in the urine due to fatty acid metabolism
no insulin present fat stores are broken down

Question 12

Why are ketones present in the urine of type I diabetics?

What can be tested for and what can be an easy sign in poorly managed type I

Answer 12

absence of insulin triglycerides are broken down to fatty acids and glycerol
some fatty acids are used in TCA cycle to generate ATP majority converted to acetoacetate in ketone pathway

B hydroxybutyrate can be detected in the urine as well as acetone in the breath (pear drop smell)

Question 13

What is type II diabetes

Answer 13

Insulin resistance
due to insulin receptors not working as they should (desensitised)

Or due to B cell dysfunction meaning insulin is no gradually no longer produced over a long period of time

Question 14

What are the characteristics of type II

Answer 14

Slow onset

associated with increased age and obesity

no ketones are present in the urine

there is a genetic predisposition

Question 15

Symptoms of type II

Answer 15

tiredness
weight loss
more frequent infections
polyuria
polydipsia
blurred vision
hyperglycaemic coma

Question 16

Treatment of type I

Answer 16

Insulin injections

Insulin is essential to maintain life

long acting insulin given to maintain a basal level
as well as fast acting insulin after meals

also manage diet

Question 17

Type II treatment

Answer 17

Lifestyle changes managing diet and increasing exercise
Drugs
insulin injections eventually

Question 18

What other factors occur due to hyperglycaemia?

Answer 18

Increased blood pressure

Increased lipid cholesterol levels in blood

Question 19

What is Retinopathy and what are some of the issues that can occur as a result of diabetes?

Answer 19

Microvascular complication of diabetes

Changes in blood glucose can result in leaky retinal blood vessels fluid back of the eye leads to macular oedema can lead to glaucoma

growth of wispy incorrectly formed blood vessels that are prone to rupturing leads to a clot forming in the eye which can lead to blindness

increased risk of developing cataracts

Question 20

What is done to prevent retinopathy?

Answer 20

Screening of diabetics

can cauterise blood vessels before they burst

managing blood glucose below 48mmol/mol

Question 21

What is diabetic nephropathy?

Answer 21

microvascular complication

high blood pressure damages glomerulus in kidney

high blood glucose can overwork the glucose filtration system in nephron

Diabetic kidney function checked by looking in urine for proteins

Question 22

What is diabetic neruopathy?

Answer 22

microvascular complication

blood vessels supplying neurones become clogged

nerve cell dies

sensation impacted in peripheral nerves leads to people not knowing they have cuts gangrene amputations

or can also get autonomic neuropathies that lead to incontinence constipation vomiting

Question 23

What are the main macro-vascular issues arising from diabetes

Answer 23

Increased risk of stroke
increased risk of heart attacks and ischaemic heart disease
Peripheral vascular disease reduced blood flow to extremities (gangrene amputations)

Question 24

What is the mechanism of insulin secretion?

Answer 24

increase glucose absorption and metabolism by B cells causes an increase in intracellular ATP

This inhibits the activity o f ATP sensitive K+ channels

Thus resulting in depolarisation of the cell

This results in opening of vg Ca2+ ion channels Ca2+ influx

Ca2+ causes release of insulin vesicles

Question 25

Why is insulin said to be a hypoglycaemic agent? | How does insulin work?

Answer 25

It lowers blood glucose Binds to insulin receptor a tyrosine kinase receptor found on most cells lots on hepatocytes and SK muscles insulin binding to two external alpha sites on receptor results in a conformational change resulting in dimerisation of the two B subunits in turn causing auto phosphorylation of tyrosine residues this activates a signal transaction cascade and phosphorylation of insulin receptor substrate proteins that ultimately leads to activation of enzymes and increased gene transcription There is increased production and expression of glut 4 transporter channels as well as increased glycogen synthesis in muscle cells

Question 26

Why can insulin not be administered orally?

Answer 26

Peptide hormone would be broken down in GI system

Question 27

How is insulin administered?

Answer 27

Parenteral route subcutaneously or intramuscularly

Question 28

How is type I diabetes managed

Answer 28

Insulin injections short term injections after meals and long term injections to maintain stable basal level

Question 29

What are the short acting insulins? | how often and when are they given?

Answer 29

Insulin or insulin lispro (less likely to be binding between insulin molecules) works rapidly after meals to lower blood glucose levels to normal level carbohydrates counted to determine how much to inject usually 2-3 times daily

Question 30

What are the long acting insulins? | how often and when are they given?

Answer 30

Insulin complexes e.g. with zinc that binds to the insulin allowing for slower release and absorption insulin glargine a micro-precipitate form onset 1-2 hours peaks 4-14 hours usually one daily

Question 31

What are some complications of insulin injections

Answer 31

risk of hypoglycaemia risk of allergy lipodystrophy fat tissue overgrows or wastes away at site of injection

Question 32

What is the principal treatment for type II diabetes

Answer 32

Lifestyle change control diet cut out sugary processed foods and decrease carbohydrate intake increase exercise levels

Question 33

Give an example of a drug that is an oral hypoglycaemic agent

Answer 33

Metformin

Question 34

How does metformin work?

Answer 34

requires presence of insulin to work works by acting like insulin increasing glucose uptake in muscles and liver cells decreases gluconeogenesis in liver cells through activation of AMP activated protein kinases reducing gene expression of enzymes involved in gluconeogenesis

Question 35

What are the advantages of metformin and disadvantages? | When is it most commonly used?

Answer 35

doesn't cause hypoglycaemia doesn't increase appetite important if treating obese diabetics can cause lactic acidosis mainly for use on obese overweight diabetics and in combination with other drugs usually

Question 36

Give an example of some sulphonylureas are these long term or short term?

Answer 36

Gliclazide Glibenclamide both longer term Tolbutamide Shorter term

Question 37

How do sulphonylureas work?

Answer 37

Bind to sulphonylurea receptor on B cells that is part of the K+ATP channel this causes the channel to close results in depolarisation of the cell results in opening of Vg Ca2+ ion channels resulting in insulin vesicle release Can also make tissues more sensitive to insulin

Question 38

What are the side effects of sulphonylureas

Answer 38

hypoglycaemia risk stimulate appetie not good in obese patients contradicted in pregnancy and breastfeeding as they can cross the placenta and effect baby

Question 39

What are thiazolidinediones?

Answer 39

Pioglitazone bind to transcription factors and effect gene transcription Primary action is in adipose tissues where they increase fatty acid uptake resulting in weight gain the decrease in FA plasma concentration seems to increase glucose uptake

Question 40

Side effects thiazolidinediones? When are they used?

Answer 40

result in weight gain found to increase fluid retention in the body increase volume of blood and can cause heart failure Often used in combination if metformin. and SU's don't work

Question 41

What is Acarbose? | When is it used?

Answer 41

a glucose inhibitor decreases carbohydrate absorption decreasing load an strain on body commonly used in obese diabetics alone or with metformin

Question 42

What are incretins

Answer 42

GI hormones that act on the pancreas to increase insulin secretion and decrease glucagon secretion

Question 43

What happens to incretins naturally

Answer 43

Broken down by an enzyme called Dipeptidyl peptidase 4

Question 44

What are gliptins how do they work

Answer 44

Gliptins act as DPP-4 inhibitors preventing incretin breakdown prolonging isulin presence and production allowing for reduction of blood glucose

Question 45

What are glucagon like peptide 1 (GLP-1) drugs? | give an example

Answer 45

Exenatide given subcutaneously is as peptide Binds to GLP-1 receptors causing an increase in insulin secretion slows gastric emptying making people feel fuller for longer also prevents the breakdown of incretins

Question 46

What are SGLT2 inhibitors? | Whats the issue with them?

Answer 46

Sodium glucose transporter -2- inhibitors E.g. canagliflozin Inhibit SGLT2 transporter in PCT of kidney increasing glucose and Na+ loss in the urine Dont really want to loose Na+ in a otherwise healthy person as it will lead to a reduction in volume which could worsen blood flow for people with Peripheral vascular disease