Chem path 17 - hypoglycaemia

Question 1

What is the management of acute hypoglycaemia dependent on?

Answer 1

How alert the patient is

Question 2

How woudl you manage an alert and oriented pt?

Answer 2

Oral carbohydrates followed by rapid acting glucose e.g. juice/sweets and then long acting carbs e.g. sandwich

Question 3

How would you manage a drowsy pt who’s swallow is still intact?

Answer 3

Buccal glucose e.g. glucogel (buccal/ sublingual given as it avoids hepatic first pass metabolism)

Question 4

How would you manage an unconscious pt or if you are concerned about their swallow?

Answer 4

IV access, 50ml 50% glucose OR 100ml 20% glucose

Question 5

if the pt starts deteriorating despite treatment what would you consider?

Answer 5

1mg IM glucagon

Question 6

If someone is NOT responding and IV access is difficult, what would you offer?

Answer 6

IM/SC glucagon

Question 7

What are the caveats to using glucagon?

Answer 7

Takes 15-20 mins to act as mobilises glycogen stores
Requires continuous monitoring
What if there are no glycogen stores in 1st place? e.g. anorexic/hepatic failure
Rebound hypoglycaemia as will cause insulin release

Question 8

Definition of hypoglycaemia normally, in diabetics and in paediatrics

Answer 8

<4.0mmol/L
<3.5 mmol/L diabetic
<2.5mmol/L paediatrics

Question 9

Outline wipple’s triad which defines hypoglycaemia

Answer 9

low glucose
symptoms
relief of symptoms with glucose administration

Question 10

2 forms of symptoms with hypoglycaemia?

Answer 10

Neuroglycopaenic - sommolence, confusion, incoordination, seizures, coma
Adrenergic - tremors, palpitations, sweating, hunger

Question 11

What happens when a patient has recurrent episodes of hypoglycaemia?

Answer 11

They develop hypoglycaemia unawareness

Question 12

What is the order of the physiological changes which take place following the detection of hypoglycaemia?

Answer 12

1. Suppression of insulin
2. Release of glucagon
3. Release of adrenaline
4. Release of cortisol, GH, ACTH etc

Question 13

What effects does glucagon have?

Answer 13

1. reduce peripheral uptake of glucose
2. gluconeogenesis
3. glycogenolysis
4. Increase lipolysis

Question 14

What happens to FFAs?

Answer 14

As there is an increase in glucose, there is also an increase in FFAs. FFAs enter the beta-oxidation cycle and generate ATP. However, if you have lots of FFAs in the body not all of them can undergo beta oxidation so some become ketone bodies.

Question 15

Where can gluconeogenesis occur other than the liver?

Answer 15

In the kidneys. This is why patients with renal failure can sometimes suffer hypos.

Question 16

How do you investigate hypoglycaemia in a healthy person?

Answer 16

Conduct a prolonged fast (72 hours), a healthy person should never become hypoglycaemic.

Question 17

How do you measure blood glucose?

Answer 17

Venous blood sample - fluoride oxalate (grey top tube),2ml blood, analysed in lab is GOLD standard

Capillary glucose - point of care test with instant results, poor precision at low glucose levels

Continuous glucose monitoring

Question 18

Causes of hypoglycaemia in non-diabetics

Answer 18

Fasting
Organ failure
Insulinoma
Factitious 
Drugs/alcohol
Extreme weight loss
Critically unwell
Post-gastric bypass

Question 19

Causes of hypoglycaemia in diabetics

Answer 19

• Medications (inappropriate insulin administration)
• Inadequate carbohydrate intake/missed meal
• Impaired awareness
• Excessive alcohol
• Strenuous exercise
• Co-existing autoimmune conditions

Question 20

Diabetic drugs associated with hypoglycaemia

Answer 20

Oral hypoglycaemic agents e.g. sulphonylureas e.g. gliclazide, GLP-1 agents
Insulin
Beta-blockers, salicylates, alcohol

Question 21

Which 2 co-morbidities are commonly associated with hypos in diabetes patients? WHy?

Answer 21

Renal/liver failure - due to impaired clearance of DM drugs –> toxicity

Question 22

What are some useful tests for differentiating the cause of hypoglycaemia?

Answer 22

Insulin, c-peptide, FFAs, ketones, drug screen

Question 23

Compare the half lives and clearance of insulin and c-peptide

Answer 23

Insulin half-life is 4-6 mins and hepatic clearance

C-peptide half-life 30 mins, renally cleared

Question 24

Hypo due to excess injected insulin would cause a high or low c-peptide?

Answer 24

LOW

Question 25

Hypoglycaemia with low insulin and low c-peptide, what are the causes? (hypoinsulinaemic hypoglycaemia)

Answer 25

This is an appropriate response to hypoglycaemia!

Starvation
Exercise
Critical illness
Liver failure
Anorexia nervosa

Question 26

Name the 3 ketone bodies

Answer 26

3-hydroxybutyrate
Acetone
Acetoacetate

Question 27

In a normal response to hypoglycaemia, what level would the ketones be?

Answer 27

HIGH

Question 28

A neonate has hypoglycaemia. What are the potential causes?

Answer 28

High ketones - prematurity (no glycogen stores), IUGR, SGA

Low ketones - inborn error of metabolism (suggests FFA metabolism defect)

Question 29

If hypoglycaemia + high insulin levels, what are the potential causes?

Answer 29

Child of GDM mother
Insulinoma 
Excess DM drugs
Beckwith Wiedemann syndrome 
Nesidioblastosis (hyperinsulinaemic hypoglycaemia due to excessive beta cell function)

Question 30

how are beta cells stimulated to release insulin?

Answer 30

Glucose crosses the cell membrane and enters glycolysis via glucokinase
Glycolysis produces ATP
Rise in ATP leads to closure of the ATP-sensitive K+ channel
Casues membrane depolarisation, calcium influx and insulin exocytosis

Question 31

MOA of sulphonylureas

Answer 31

Bind to ATP-sensitivt-K+ (Sur1) channel and makes it close indepednent of ATP so you get insulin release

Question 32

Insulinoma - glucose, insulin and c-peptide level?

What syndrome is it associated with?

Answer 32

Glucose - low
Insulin and C-peptide - high
MEN1

Question 33

• 60yo cachectic man unconscious, smoker, glucose 1.9mmol/L
• Hypoglycaemia persists despite glucose infusion
• Insulin & c-peptide undetectable, FFA undetectable, ketones -ve

Answer 33

Non-islet cell tumour hypoglycaemia (paraneoplastic, big IGF-2 secretion–> stimulation of insulin receptor)

Question 34

What is post-prandial/reactive hypoglycaemia and when does it occur?

Answer 34

hypoglycaemia after food intake. Can happen after gastric bypass, hereditary fructose intolerance, EARLY SIGN OF T2DM

Question 35

When should you take bloods in patients with hypoglycaemia?

Answer 35

During the hypoglycaemic episode unless it delays treatment