141 - Diabetes Type II

Question 1

What 4 diagnostic tests are used in diabetes?

Answer 1

RPG - Random plasma glucose + symptoms (over 11.1)
Fasting plasma glucose (over 7)
OGTT - Oral glucose tollerance test - gold standard (over 11 diagnose, over 6 monitor/further tests)
HbA1c - Glycosylated haemoglobin (over 6.5)

Question 2

What are the pros of using glucose to test rather than HbA1c?

Answer 2

Diabetes is a glucose disease
Lots of data already, international comparison
Cheap and easy

Question 3

What are the pros of using HbA1c rather than glucose?

Answer 3

Stable result
Time averaged
Reproducible
No fasting needed

Question 4

What are the cons of using Glucose rather than HbA1c?

Answer 4

Need to fast before test

Can have pre-analytical problems

Question 5

What are the cons of using HbA1c rather than glucose ?

Answer 5

Can’t use if anemic - as red blood cell levels wrong
Can’t use if there is renal impairment, haemolysis, blood transfusion.
In pregnancy levels get altered as blood concentration changes.

Question 6

Would you suggest to just do both a random plasma glucose and a HbA1c at the same time to be double sure of a diagnosis?

Answer 6

No. Correlation between the tests is poor - stick to one.

Question 7

How long a history does a HbA1c value indicate?

Answer 7

120 days - 4 months
Lifespan of a RBC
but 50% of result is from last month.

Question 8

What hormones are involved in glucose homeostasis?

Answer 8

Insulin - B cells in panc, removes glucose from blood, enhances peripheral uptake

Glucagon - alpha cells in panc. Stimulates hepatic glycogenolysis and gluconeogeneis - increased available glucose

Incretin hormones - released during glycaemic attack, eg. glucocorticoids, cortisol, GH

Question 9

When you eat insulin is released in 2 phases, describe them.

Answer 9

1st phase - rapid, 5-10 minutes, preformed insulin is released in a big peak
2nd phase, after initial insulin is used the pancrease starts producing and releasing insulin in a more sustained mannor

Question 10

How is the insulin response stimulated when you eat?

Answer 10

Glucose is detected by L cells in the small intestine mainly.
They produce GLP-1, an incretin

GLP-1 binds to receptors in the pancrease which increases insulin production and decreases glucagon production

Question 11

In type II diabetes what occurs to the insulin response?

Answer 11

initially - 1st phase lost
Then 2nd phase response is reduced and loss

The is evolving B cell dysfunction - insulin sensitivity and glucose intollerance develops

Question 12

How does glucose resistance develop?

Answer 12

Glucose must be transported across membranes via insulin receptors.

You can get defects in physphorylation at these receptors, so glucose cant respond to insulin by being transported into a cell - resistance

Question 13

What happens if you are given IV glucose, and don’t eat it?

Answer 13

You don’t get same insulin response, as L receptors not activated so GLP-1 not released

Question 14

What happens to the kidney’s function when there is too much glucose?

Answer 14

There is a threshold of reabsorption of glucose (due to SGLT2 rate limiting receptor), so if too much, glucose is excreted in the urine.

Question 15

What happens to the kidney function in Type II diabetes?

Answer 15

You get overexpression of SGLT2, the rate limiting receptor in glucose reabsorption, so more glucose is reabsorbed, so you don’t lose glucose in urine until your blood glucose is even higher.

Question 16

What symptoms do you get with diabetes?

Answer 16

Osmotic symptoms - Thirst, increased micturation (weeing) as body tries to balence out glucose osmotic potential
Headaches, tirdness, sliggishness as increased blood glucose makes circulations sluggish all round body

Question 17

What risk factors are there for diabetes?

Answer 17

FH
High BMI
Smoking
Alcohol
Sedentary lifestyle

Question 18

What does chronic hyperglycaemia lead to?

Answer 18

Microvascular complications - Retinopathy, Nephropathy, Neuropathy

Macrovascular complications - Coronary artery disease
Cerebrovascular disease (stroke)
Peripheral vascular disease

Question 19

A patient only manages to reduce their HbA1c by 0.9%, is that still useful?

Answer 19

Yes, 0.9% reduction reduces microvascular complications by 25%

Question 20

What is the 1st line drug used in Type II diabetes?

Answer 20

Metformin - a biguanide

Improves insulin’s action

Question 21

What 2nd line drugs (3) might you use in type II diabetes?

Answer 21

Gliclazide (or Glimperide) - a Salphonylurea
Stimulates B cells to produce more insulin

or
Piogitazone - a Thiazolidinedione TZD - increases peripheral sensitivity to insulin

or

Sitagliptin - a DDP-4 inhibitor - an incretic based therapy to stop GLP-1 degredation

Question 22

Can you get a hypo on metformin?

Answer 22

No - safe to use!

Question 23

Apart from glicalazie, what other drug class increases insulin secretion?

Answer 23

Repaglinide, a Metiglinide

Question 24

Name an alpha-glucosidase inhibitor, what does it do?

Answer 24

Acarbose

Delays glucose absorption

Question 25

What are the 2 incretin based therapies used in type II diabetes?

Answer 25

DDP-4 inhibitors (Sitagliptin)

GLP-1 receptor agonists (Byetta, Lirglutide)

Question 26

When would you consider insulin therapies?

Answer 26

In later stages of type II diabetes

When other drugs havent been effective

Question 27

What drugs are available that act on kidney function in type II diabetes?

Answer 27

SGLT2 inhibitors - reduce glucose reabsorption so you excrete more in urine
eg. Canagliflozin

(increased UTI risk)

Question 28

What proportion of type II diabetics succumb to cardiovascular complications?

Answer 28

75%

Question 29

Which factors is most important in terms of reducing CVD in type II diabetes?

• Glycaemia
• Hypertension
• Cholesterol
• eGFR

Answer 29

Cholesterol

Question 30

Why must you rotate insulin injection points?

Answer 30

They can cause far hypertrophy or loss - lipoatrophy - which changes the insulin’s absorption

Question 31

A man who has diabetes keeps getting intermittent pain in his lower calves while walking, what may he have?

Answer 31

Intermittent claudication

Question 32

Where does painful peripheral neuropathy first effect?

Answer 32

The longest nerves - the feet

Question 33

What did the UK prospective diabetes study show?

Answer 33

Although originally not showing anything on its 10 year follow up showed that tight control improves side effects and complications of diabetes

Question 34

Why might someone presenting with suspected type II diabetes have eye problems, if retinopathy develops slowly over a long time?

Answer 34

Hyperglycaemia can directly effec they eye, as glucose enters the lens, pulling more water in, causing a refractive change.

With good blood sugar control this will improve

Question 35

What different types of ulcer do you get in diabetes?

Answer 35

Neuropathic - as no pain from peripheral neuropathy big ulcers can develop from callouses. Usually over pressure points

Ischaemic

Venous (same risk as normal population)

Question 36

What is necrobiosis?

Answer 36

A lesion specific to diabetes, mainly on the lower legs, a fryable skin lesion that wears away - dissapears with time.

Question 37

What BP target is there in type 2 diabetes?
160/80
140/80
140/60
120/60

Answer 37

140/80

Question 38

What BP target is there in type II diabetes after an MI/had a vascular event?

Answer 38

130/80