Hypoglycaemia

Question 1

What is the acute management for hypoglycaemia in the following scenarios:

1. Adult is alert and orientated
2. Adult is drowsy/confused but swallow intact
3. Adult is unconscious or concerned about swallow

Answer 1

Alert

• Oral carbohydrates
• Rapid acting e.g. juice/sweets
• Longer acting - sandwich

2. Drowsy/confused but intact swallow

• Buccal glucose e.g. hypostop/glucogel
• Start thinking about IV access

3. Unconscious or concerned about swallow

• IV access
• 50ml, 50% glucose mini-jet or 100mls 20% glucose

Question 2

What are the symptoms of hypoglycemia in the following:

1. Adrenegic symptoms
2. Neuroglycopaenic symptoms

Answer 2

1. Adrenergic

• Tremors
• Palpitations
• Sweating
• Hunger

2. Neuroglycopaenic

• Somnolence
• Confusion
• Incoordination
• Seizures, coma

Question 3

What is the definition of low glucose?

Answer 3

Low glucose can be any level of glucose that causes symptoms

Question 4

What is the counter-regulation systems in place in response to low glucose?

Answer 4

Reduced insulin, increased glucagon leading to:

• Reduce peripheral uptake of glucose
• Increase glycogenolysis
• Increase gluconeogenesis
• Increase lipolysis

Leads to increased glucose and increased Free fatty acids

Increased in FFA caused by beta oxidation and increased ketone body production

Low neuronal glucose sensed in hypothalamus

• Sympathetic activation - catecholamines
• ACTH, cortisol and GH production

Question 5

What occurs first in response to hypoglycaemia?

1. Suppression of insulin
2. Release of glucagon
3. Release of adrenaline
4. Release of cortisol

Answer 5

1. Suppression of insulin

Question 6

How can glucose be measured?

Answer 6

Laboratory:

• Grey top (flouride oxalate)
• venous sample - 2mls of blood
• Gold standard to make diagnosis

Blood glucose meter

• Point of care device
• Instant result using capillary blood
• However, has poor precision at low glucose lebels

Question 7

1. What is the most common cause of hypoglycaemia?
2. What else can cause hypoglycaemia?

Answer 7

1. Diabetes
2. Other causes

• Medications
• Inqdequate CHO/missed meal
• Impaired awareness
• Excessive alcohol
• Strenuous exercise
• Co-existing autoimmune conditions

Question 8

Name the different diabetic medications that can cause hypoglycaemia

Answer 8

Oral Hypoglycaemia:

• Sulphonylureas
• Meglitinides
• GLP-1 agents

Insulin

• Rapid acting with meals - inadequate meal
• Long acting - hypos at night or in between meals

Other drugs

• Beta blockers
• Salicylates
• Alcohol (inhibits lipolysis)

Question 9

C peptide:

1. is the cleavage product of insulin
2. Is secreted in equimolar amounts to insulin
3. has a half lifeof 2 hours
4. interferes with insulin measurement

Answer 9

2. is secreted in equimolar amounts to insulin

Question 10

What is the half life and clearance of the following:

1. Insulin
2. C -peptide

Answer 10

1. Insulin

• Half life = 4-6 minutes
• Hepatic clearance

C-peptide

• Half life = 30 mins
• Renal clearance

Question 11

Hypoglycemia due to excess injected insulin would results in

1. A low C-peptide
2. A high C-peptide

Answer 11

Low C-peptide as the body is suppressing insulin and so suppressing production due to hypoglycaemia

Question 12

Case

20 year old female, BMI 17kg/m2. Lanugo hair noted. Finger prick glucose - 3.8mmol/l. Routine bloods taken. An hour later her plasma glucose is 2.6mmol/l

1.What is the most likely cause of her low blood sugar?

1. Undertakes strenuous exercise regularly
2. Insulinoma
3. Anorexic with poor liver glycogen stores
4. Laxative abuse
5. What would be the insulin and C-peptide if they had been measured?

Answer 12

1.

3. Anorexic with poor liver glycogen stores
4. Low insulin and low C-peptide

Question 13

What are some causes of hypoglycaemia with low insulin and low c-peptide?

Answer 13

• Fasting/starvation
• Strenuous exercise
• Critical illness
• Liver failure
• Anorexia nervosa

Question 14

Case

1 day old neonate, who is jittery and not feeding well. Premature at 34 weeks gestation. Lab glucose 1.9mmol/l

Glucose improved on feeding, but low blood glucose 4 hours after feed. 3 hydroxybutyrate measured at time of hypo and was negative

1. What is 3-hydroxybutyrate
   a) End product of insulin metabolism
   b) A free fatty acid
   c) A triglyceride
   d) A ketone body
   e) A component of artificial nutrition

Answer 14

d) a ketone body

Question 15

What does the absence of ketones signify when the glucose in a baby is 1.9 and ketones are negative?

a) insulin deficiency
b) fatty acid oxidation defect
c) starvation

Answer 15

b) Fatty acid oxidation defect

Question 16

What are the causes of neonatal hypoglycaemia?

Answer 16

Explainable

• Premature, co-morbidities, IUGR, SGA
• Inadequate glycogen and fat stores
• Should improve with feeding

Pathological:

• Inborn metabolic defects

Question 17

Neonatal hypoglycaemia with suppressed insulin and C-peptide. FFA raised, but no ketones.

What are some inherited metabolic disorders?

Answer 17

• FAOD - no ketones produced
• GSD type 1 - gluconeogenetic disorder
• Medium chain acyl coA dehydrogenase def.
• Carnitine disorders

Question 18

What can cause inappropriate inslin levels?

Answer 18

• Islet cell tumors - insulinoma
• Drugs - insulin, sulphonylurea
• Islet cell hyperplasia
  
  • Infant of diabetic mother
  • Beckwith Weidemann syndrome
  • Nesidioblastosis

Question 20

Describe normal insulin secretion

Answer 20

Insulin is released from beta cells of the pancreas. Glucose are taken up into Beta cells where it is broken down and ATP released. ATP driven potassium channels controls insulin release from beta cells. K influx, driven by ATP and influx of calcium through a Ca ion channel. This causes membrane depolaization, and allows vesicles that contain synthesized insulin to bind with the cell membrane and release insulin

Question 21

How do sulphonylureas work?

• Which subunit do they affect?

Answer 21

• Sulphonylureas primary mode of action is to close the ATP driven K channel, by binding to Sur1 subunit of the ATP driven K channel
• This acts to close the ATP driven K channel, and therefore stimulates the beta cells of the pancreas to keep releasing insulin more than it usually would

Therefore, sulphonlyureas are hypoglycaemic diabetic drugs

Question 22

Describe an insulinoma including associations and treatment

Answer 22

• An insulinoma is a tumor of the beta cells of the pancreas
• 1-2 million/year
• Usually a small solitary adenoma
• 10% are malignant
• 8% associated with MEN1
• Diagnosis is based on biochemistry and localisation
• Treatment is usually resection
• Insulin is high, C-peptide is high and glucose is low

Question 23

Case

9 year old boy brought in fitting.

Glucose 1.9mmol/l, insulin 205mu/L, C-peptide <33pmol/L

What is the most likely cause of the low blood glucose?

1. Glucose consumption during epileptic fit
2. Stress response
3. Factitious insulin
4. Need more information

Answer 23

3. Factitious insulin

Inappropriate insulin and C-peptide. Insulin is high but C-peptide is low.

Factitious insulin/oral hypoglycemic usage always needs to be considered - insulin and drugs

Question 24

Case

60 year old cachetic man found unconscious, smoker.

Glucose 1.9mmol/L

Hypoglycemia persists so a glucose infusion is given. Insulin and C-peptide are undetectable, free fatty acids are undetecable, ketones negative

Which diagnosis is most likely?

1. Benign insulinoma
2. Non-islet cell tumor hypoglycemia
3. Malignant insulinoma
4. Addison’s disease
5. Panhypopituitarism

Answer 24

2. Non-islet cell tumour hypoglycemia
   * Glucose, insulin, C-peptide, FFA and ketones are all reduced

Question 25

Describe Non-islet cell tumour hypoglycemia

Answer 25

* Tumours that cause a paraneoplastic syndrome * Secretion of 'big-IGF-2' * Big IGF-2 binds to IGF-1 receptpr and insulin receptor * Mesenchymal tumours (mesothelioma/fibroblastoma) * Epithelial tumours (carcinoma) Everything is reduced: * Glucose, insulin, c-peptide, FFA and ketones

Question 26

Describe autoimmune insulin syndrome

Answer 26

* Antibodies directed to insulin, sudden dissociation and may precipitate hypoglycemia * More common in Japan * Can be caused by certain drugs e.g. hydralazine, procainamide Antiboodies to insulin resistance tend to present with insulin resistance, while antibodies to insulin itself tends to present with hypoglycemia

Question 27

What are some genetic mutations that causes high insulin?

Answer 27

* Glucokinase activating mutation * Congenital hyperinsulinemism * KCNJ11/ABCC8 * GLUD-1 * HNF4A * HADH

Question 28

What can is and can cause reactive/post-prandial hypoglycemia?

Answer 28

* Reactive/post-prandial hypoglycemia is hypoglycemia following food intake Causes: * Can occur post-gastric bypass * Hereditary fructose intolerance * Early diabetes * In insulin sensitive individuals after exercise or a large meal

Question 29

Case Type 1 diabetic 5 years, previously well controlled and now has recurrent hypos in the morning. Hba1c 6.0%, noted to be a lot more tired than usual What should be done next? 1. Review insulin dosing 2. Review injection technique 3. Consider pump therapy 4. Perform a short synacthen test 5. All of the above

Answer 29

5. All of the above Always check technique, always check dosage, always consider other treatments and potential other causes e.g. Addisons