Endocrine - diabetes

Question 1

What are the types of insulin available?

Answer 1

Rapid-acting
Short-acting
Intermediate-acting
Long-acting
Continuous sub-cutaneous insulin infusion (insulin pump)

Question 2

What are the regimes available for insulin therapy?

Answer 2

Twice daily
Three times daily
Four times daily

Question 3

When do you take the twice daily regime?

Answer 3

Rapid acting mixed with intermediate acting 
Before breakfast (BB) and evening meal (BT)

Question 4

What is the three times daily regime?

Answer 4

Rapid acting mixed with intermediate acting Before breakfast
Rapid acting Before dinner
intermediate acting at bedtime

Question 5

What is the four times daily insulin regime?

Answer 5

Short acting Before breakfast, lunch and dinner

Intermediate BBed or long acting insulin at a fixed time once daily

Question 6

What is the basal bolus therapy and who is it good for?

Answer 6

Long acting insulin in the background
Rapid acting insulin calculated before meals
Very good for shift workers who don’t know when they will eat

Question 7

What are the cautions with insulin pumps?

Answer 7

No background insulin

Must check blood glucose themselves

Question 8

What is the glucose needed to drive?

Answer 8

5 to drive (greater than 5mmoles)

Question 9

What is the lowest blood glucose a diabetic should ever go to?

Answer 9

4s the floor

Question 10

What are the main causes of hypoglycaemia?

Answer 10

Food (too little./wrong type)
Activity
Insulin (too much or taken poorly)

Question 11

What are the symptoms of hypogylcaemia?

Answer 11

Sweating
Palpitations
Shaking
Hunger
Confusion
Drowsiness
Speech difficulty
Incoordinatio
Nausea

Question 12

What are the symptoms of a DKA?

Answer 12

Polyuria
Polydipsia
Weakness
Weight loss
Nausea
Abdominal pain
Breathlessness

Question 13

What are the signs of a DKA?

Answer 13

Dry mucus membranes
Sunken eyes
Tachycardia
Hypotension
Ketotic breath
Altered mental state
Hypothermia

Question 14

What are the complications of DKA?

Answer 14

Hyper and hypokalaemia
Hypoglycaemia
>Rebound ketosis
>Arrhythmias
>Acute brain injury
Cerebral oedema
>Children more susceptible
>70-80% diabetes related deaths in children <12
Aspiration pneumonia
Arterial and venous thromboembolism
ARDS

Question 15

How do you treat a DKA?

Answer 15

Measure glucose / U and E’s / ketones / bicarbonate / arterial blood gas
Give iv saline (5 l in 24 hours)
Give iv insulin (drives glucose and potassium into cells)
Give iv potassium in saline
May need antibiotics
Consider heparin, NG tube
Mortality Rate 2%

Question 16

Which drugs improve the action of insulin?

Answer 16

Biguanides

Thiazolidiones

Question 17

What drugs improve the excretion of glucose?

Answer 17

SGLT2 inhibitors

Question 18

Which drugs improve insulin release?

Answer 18

Sulphonylureas
Metglinides
Incretin mimics
DPPIV inhibitors

Question 19

What is metformin?

Answer 19

A biguinide
>therefore improves insulin sensnitivity
Has half life of 6 hours

Question 20

How does metformin improve the sensitivity of insulin?

Answer 20

Affects glucose production, decrease fatty acid synthesis
Improves receptor function
Inhibits gluconeogenic pathways

Question 21

What are the advantages of metformin?

Answer 21

Improves cardiovascular outcomes and mortality in obese T2 DM
Cheap  
Efficaceous
Normally well tolerated
Not associated with weight gain
HbA1c by 12 – 17% reduction 
Also used in pregnancy now

Question 22

What are the disadvantages of metformin?

Answer 22

Risk of lactic acidosis by inhibiting lactic acid uptake by liver especially in
>Hypoxia
>Renal failure (CI if creat<150)
>Hepatic failure
>Alcohol abuse
GI side effects 20 – 30 %
Risk vitamin B12 malabsorption

Question 23

What is the mechanism of action of sulphonylureas?

Answer 23

Binds to sulfonylurea receptors (SUR-1) on functioning pancreatic beta-cells.
Binding closes the linked ATP-sensitive potassium channels
Decreased potassium influx depolarization of the beta-cell membrane.
Voltage-dependent calcium channels open and result in an influx of calcium
Translocation and exocytosis of secretory granules of insulin to the cell surface

Question 24

What are the advantages of sulphoylnureas?

Answer 24

Used with metformin
Rapid improvement in control 
Rapid improvement if symptomatic
Rapid titration
Cheap 
Generally well tolerated

Question 25

What are the disadvantages of sulphonylureas?

Answer 25

``` Risk of hypoglycaemia Weight gain Caution in renal and hepatic disease CI in pregnancy and breastfeeding. SE include >Hypersensitivity and photosensitivity reactions >Blood disorders ```

Question 26

What is the mechanism of action of thiazolidinediones?

Answer 26

selectively stimulates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) and to a lesser extent PPAR - alpha modulates the transcription of the insulin-sensitive genes involved in the control of glucose and lipid metabolism in the muscle, adipose tissue, and the liver. reduces insulin resistance in the liver and peripheral tissues; increases the expense of insulin-dependent glucose; decreases withdrawal of glucose from the liver; reduces quantity of glucose, insulin and glycated haemoglobin in the bloodstream.

Question 27

What are the advantages of pioglitazone?

Answer 27

``` Good for people if insulin resistance significant HbA1c by 0.6-1.3% Cheap Cardiovascular safety established (Contrast with rosiglitazone) ```

Question 28

What are the disadvantages of pioglitazone?

Answer 28

``` Increase risk of bladder cancer >Caution in those of increased risk bladder cancer (Age, industry etc) Fluid retention - CCF Weight gain Fractures in females >Small increased risk >TZDs affect bone turnover >Reduced BMD >Initial report were of increased distal fractures in women ```

Question 29

What is the mechanism of action of gliptins (DDPV inhibitors)?

Answer 29

Inhibits DD4 enzyme which degrades incretins Therefore increases active incretin levels Results in increase in insulin release and decrease in glucagon

Question 30

What are the advantages of gliptins?

Answer 30

``` Usually well tolerated Can be used as 2nd or 3rd line agent Can be used in renal impairment No risk of hypoglycaemia Weight neutral ```

Question 31

What are the disadvantages of gliptins?

Answer 31

Trial data shows relatively small effects on glycaemic control CI in pregnancy and breastfeeding. Possible increased risk of pancreatitis and pancreatic cancer SE: nausea

Question 32

What is the mechanism of action of GLP-1 analogues?

Answer 32

Injectable analogues of GLP-1 resistant to enzymatic half life Therefore greatly enhanced biological half life Incretins stimulate the pancreas for longer Results in more insulin release

Question 33

What are the advantages of GLP-1 analogues?

Answer 33

Weight loss No risk of hypoglycaemia 3rd line agent Can be used with basal insulin

Question 34

What are the disadvantages of GLP-1 analogues?

Answer 34

``` Injection Very expensive Possible increased risk of pancreatitis and pancreatic cancer CI in pregnancy and breastfeeding. SE: Nausea, vomiting ```

Question 35

What is the Mechanism of action of SGLT2 inhibitors (gliflozins)?

Answer 35

Prevent glucose reabsorption at proximal tubule | Results in a lot more urinary excretion of glucose

Question 36

What are the effects of SGLT2 inhibitors?

Answer 36

``` Gets rid of glucose/more glycosuria >Lowers HbA1C Gets rid of water/osmotic diuresis >(POSTURAL) hypotension, dehydration Gets rid of calories by wasting glucose >Weight loss with same intake Less uptake of sodium >Lowers systolic blood pressure Increases risk of urinary infection >Cystisis + candidiasis ```

Question 37

What are the advantages of SGLT2 inhibitors?

Answer 37

``` Weight loss No risk of hypoglycaemia Good effects on glycemic control May have beneficial effect on cardiovascular morbidity & mortality 2nd or 3rd line agent Can add to insulin regimens in T2DM ```

Question 38

What are the disadvantages of SGLT2 inhibitors?

Answer 38

``` Expensive SE: UTI, fungal infections, osmotic symptoms Risk of digital amputation Risk of DKA CI in pregnancy and breastfeeding. Cannot use in renal impairment ```