Diabetes type 2

Question 1

What are the main glucose stores?

Answer 1

Liver
Fat
Muscle

Question 2

What happens in T2D?

Answer 2

Insulin resistance and beta-cell dysfunction

Question 3

What does insulin normally do?

Answer 3

Binds to receptors triggering production of glucose transport proteins to allow glucose to enter cell

Question 4

What happens in insulin resistance?

Answer 4

Receptor is not as responsive to the insulin molecule

Question 5

What can cause insulin resistance?

Answer 5

Ectopic Fat Accumulation
Increased FFA circulation
Reduction in insulin-stimulated glycogen syntheses

Question 6

What is beta-cell dysfunction?

Answer 6

Reduced ability of beta-cells to secrete insulin in response to hyperglycaemia

Question 7

What does insulin resistance lead to?

Answer 7

Glucotoxicity (hyperg)

Lipotoxicity (elevated FFA, TG)

Question 8

What body shape is more likely to get type 2 diabetes?

Answer 8

Apple as opposed to pear

Question 9

What does Central Adiposity associated with?

Answer 9

High blood pressure
High triglycerides
Low HDL
Insulin resistance

Question 10

How long does the average person have diabetes T2 before they are diagnosed?

Answer 10

9-12 years

Question 11

What are DT2 complications are present at diagnosis?

Answer 11

Retinopathy - 21%
ED - 20%
Neuropathy - 18%
nephropathy - 12%

Question 12

Describe the therapy staircase of DT2?

Answer 12

1. Diet % Exercise
2. Oral monotherapy
3. Oral combination
4. Injectable & oral therapy

Question 13

What changes in lifestyle play a part in diabetes treatment?

Answer 13

Weight loss
Exercise
Smoking cessation
Improve diet

Question 14

What is Metformin?

Answer 14

A biguanide,
derived from guanidine
Improves sensitivity to insulin

Question 15

What is the starting metformin does?

Answer 15

500mg Od or BD

Question 16

What are the effects of metformin?

Answer 16

Reduces HbA1c by 15-20
Doesnt cause hypos
Prevents macro and micro vascular complications

Question 17

What are the additional effects of metformin?

Answer 17

Reduces triglycerides and LDL
reduction in BP
Safe in pregnancy

Question 18

What are side effetcs of metformin?

Answer 18

GI effects 
Interferes with vitamin B12 and folic acid absorption (anaemia is rare)
Lactic acidosis 
Liver failure
Rash

Question 19

Describe sulphonylureas (SU)

Answer 19

Glicazide 40mg -160mg OD

Glipizide 2.5mg-15mg

Question 20

What are the effects of SU’s?

Answer 20

Reduces HbA1c by 15-20
Increasing insulin secretion
More rapidreduction in hyperg
Prevents micro but not macro

Question 21

What are side effects of SU’s?

Answer 21

Hypog
Weight gain
GI

Question 22

What are thiazolidinediones? (TZDs)

Answer 22

Only available agent is pioglitazone 15-45mg OD

Question 23

What are the TZDs effects?

Answer 23

Hyperg - HbA1c down by 15-20
Weight gain
HF
prevention of macro but not micro

Question 24

Give an example of an SGLT2 inhibitor

Answer 24

Dapagliflozin (aka Forxiga)

Question 25

What do SGLT2 inhibitors act upon?

Answer 25

Incretin pathway

Question 26

Where is Exenatide (Byetta) from?

Answer 26

Exandin found in Gila Monsters

Question 27

What are some benefits of GLP-1 receptor agonists?

Answer 27

Promote insulin secretion from pancreas without hypoglycaemia Suppress glucagon (which is increased in T2DM) Decrease gastric emptying – early satiety Act on hypothalamus – reduce appetite – resulting weight loss (~3kg)

Question 28

What are some of the dis-benefits of GLP-1 receptor agonsists?

Answer 28

Nausea – usually resolves in most by 6-8 weeks Injectable Pancreatitis, Pancreatic Cancer

Question 29

Describe the DPP-IV inhibitors?

Answer 29

Orally active | Less potent than GLP-1 mimetics – can only work on what’s there and GLP-1 levels are low in T2DM

Question 30

What are examples of DPP-IV inhibitors?

Answer 30

Vildagliptin, Sitagliptin, Saxagliptin, Linagliptin

Question 31

What are some benefits of DPP4 inhibitors?

Answer 31

Promote insulin secretion from pancreas without hypoglycaemia Suppress glucagon (which is increased in T2DM) Weight neutral

Question 32

What are some dis-benefits of DPP4 inhibitors?

Answer 32

Very limited side effects Not that potent No weight loss – No weight gain Pancreatitis, Pancreatic Cancer

Question 33

What are some examples of SGLT2 inhibtors?

Answer 33

DAPAGLIFLOZIN (ForxigaTM) CANAGLIFLOZIN (Invokana) EMPAGLIFLOZIN (Jardiance