Diabetes Mellitus

Question 1

What is DM type 1?

Answer 1

Associated with onset at young age
Caused by destruction of beta-cells following certain viral infections or due to an autoimmune process
Characterised by an inability of the beta-cells to produce insulin

Question 2

What are insulin preparations?

Answer 2

Human insulin analogues
Short acting insulins
Intermediate and long-acting insulins

Question 3

What are human insulin analogues?

Answer 3

Modified insulin peptides (insulin lisper and insulin aspart)- have a rapid onset but short duration of action
May be injected before a meal or when necessary after a meal

Question 4

Who are human insulin analogues suited to?

Answer 4

Increase flexibility and are useful for patients prone to pre-lunch hypoglycaemia and those who eat late in the evening and may be at risk of nocturnal hypoglycaemia

Question 5

What are short acting insulins?

Answer 5

Soluble insulins have relative short-lived effects of 6-8 hours, with peak effects at 2-5 hours
Given 15-30 minutes before meals

Question 6

What are intermediate and long-acting insulins?

Answer 6

Combination of insulin with protamine give rise to intermediate acting insulin (isophane insulin)
Binding to zinc gives intermediate to long acting insulin and combination with protamine plus zinc gives long acting insulin

Question 7

What are long-acting insulins?

Answer 7

Crystalline insulin zinc suspensions

Question 8

What are intermediate long acting insulins?

Answer 8

Bisphasic preparations contain both an intermediate acting agent (isophane insulin) and a shorter acting form (soluble insulin)

Question 9

What is a twice daily regimen?

Answer 9

2 daily injections, one 30 mins before breakfast and one before evening meal of short and long acting insulins in combination
2/3s of the insulin given as the morning dose
Most common regimen

Question 10

What are multiple dosing regimens?

Answer 10

Single dose of medium acting insulin at bedtime
Doses of short acting insulin given 30 mins before each meal
Basal bolus regimen

Question 11

What is the alternative multiple dosing regimen?

Answer 11

Short-acting mixed with intermediate acting insulin is given before breakfast
Short acting given before evening meal
Intermediate acting given at bedtime

Question 12

What is a single daily regimen?

Answer 12

1 daily intermediate acting insulin before breakfast or at bedtime, with or without a short acting

Question 13

Who is a single daily regimen for?

Answer 13

T2DM who are unable to control their blood glucose with anti diabetic drugs

Question 14

When is insulin requirement increased?

Answer 14

Stress
Infection
Accidental or surgical trauma
Puberty (effect fo growth hormone)
Last 2 trimesters of pregnancy

Question 15

When is insulin requirement reduced?

Answer 15

Coeliac disease
Renal or hepatic impairment
Endocrine disorders (Addison’s)

Question 16

How is insulin administered?

Answer 16

IV (hospital/acute, honeymoon period less insulin required)
SC (different insulins can be mixed, largely replaced by injection pens and biphasics)
Insulin pumps (cont sc, good in difficult to control)

Question 17

What can subcutaneous injections of insulin lead to?

Answer 17

Changes to the skin
Site of multiple injections there may be lipohypertrophy, leading to unpredictable insulin absorption
Patients should rotate the sites used

Question 18

What is T2DM?

Answer 18

Increased insulin resistance
Strong family association
B-cells still produce insulin but there may be a loss of cells of reduced glucose sensitivity
>40
Other associated diseases (obesity, hypertension, hyperlipidaemia)

Question 19

What is the management of mild T2DM?

Answer 19

Reduce amount of simple carbohydrates
Limit intake of mono and disaccharides, increase non-starch polysaccharides
Reduce intake of fat to reduce risk of atherosclerosis, fat is 30-35% calories intake and carbohydrate is 50-55%
Weight loss in obese
Increased exercise
Antidiabetic drugs used after 3 months

Question 20

What are sulphonylureas?

Answer 20

Gibenclamide, glicazide, tolbutamide
Increase insulin secretion
Inhibit ATP-K channels

Question 21

How do sulphonylureas work?

Answer 21

Glucose leads to ATP production which inactivate kATP channels, leading to cellular depolarisation, which results in calcium influx and insulin secretion
When glucose is low, ATP falls and ADP rises, channels open, with membrane hyper polarisation and this decreases insulin
Sulphonylureas bind to a receptor associated with these channels, resulting in channel closure, leads to insulin release

Question 22

What are the side effects of sulphonylureas?

Answer 22

Weight gain (increase insulin resistance) avoid in obesity
Awareness may be lost when using B-blocker
Hypoglycaemia (in elderly, missing meals, long acting agents (glibenclamide))

Question 23

What are meglitinide analogues

Answer 23

Nateglinide, repaglinide

Act on b-cells to cause closure of kATP channels, leading to depolarisation and insulin release

Question 24

When are meglitinide analogues given?

Answer 24

Rapid rate of onset given at meal times to stimulate post-prandial insulin secretion, relatively short lived
Effects may be enhanced by the patient having a meal, referred to a prandial glucose regulators (PGRs)

Question 25

What are biguanides?

Answer 25

Metformin
Action less clear: may activate AMP-kinase
Drug if choice for obese patients (no weight gain)
Do not use in renal impairment
Doesn’t cause hypoglycaemia

Question 26

What are thiazolindiediones (glitazones)?

Answer 26

Glitazones: pioglitazone
Activate nuclear peroxisome proliferator-activated receptors gamma (PPAR-y) which alters gene expression and results in insulin-like effects
Insulin sensitisers which work by enhancing glucose utilisation in tissues and reduce insulin resistance

Question 27

What are the effects of thiazolindiediones (glitazones)?

Answer 27

Reduced hepatic glucose output
Increased glucose transporters (GLUT) in sskeletal muscle with increased peripheral glucose utilisation
Increased fatty acid uptake into adipose cells

Question 28

What do you have to be careful with when using thiazolindiediones (glitazones)?

Answer 28

Liver function should be monitored
Shouldn’t be used as 2nd line therapy unless a patient can’t tolerate metformin + sulphonylurea
Used when either metformin or sulphonylurea is not tolerated

Question 29

What the steps for management in T2DM?

Answer 29

Step 1: 3 months of diet control
Step 2: Normal renal function- metformin
Renally impaired- sulphonylurea 
Step 3: 2 from metformin, sulphonylurea or glitazone 
Blood pressure control throughout

Question 30

What is used to reduce cardiovascular complications in diabetes?

Answer 30

ACEI first line
Thiazides, B-blockers, calcium channel blockers are equally effective
Simvastatin

Question 31

Which patients should receive an ACEI?

Answer 31

All patients with T1DM and microalbuminuria

AT1 receptor antagonists can substitute if not tolerated

Question 32

Which patients are likely to develop diabetic neuropathy?

Answer 32

Albumin in the urine and/or increased plasma creatine levels which is accompanied by retinopathy

Question 33

What are the targets for patients who are likely to develop diabetic neuropathy?

Answer 33

Glycated haemoglobin (HbA1c) <6.5-7.5%
BP <135/75
ACEI given for renal and cardiovascular protection