Hypoglycaemia Flashcards
What is the acute management of hypoglycaemia in alert and oriented adults?
Oral Carbohydrates
Rapid acting; juice / sweets
Longer acting; sandwich
What is the acute management of hypoglycaemia in drowsy/ confused but in tact swallow adults?
Buccal glucose
e.g. Hypostop / glucogel
…start thinking about IV access
What is the acute management of hypoglycaemia in unconscious/ poor swallow adults?
IV access
50 ml, 50 % glucose mini-jet
Or 100 mls 20% glucose
What are caveats to acute treatment?
Treat, monitor, treat, monitor….
Beware extravasation of IV glucose: irritant, phlebitis
Glucagon mobilises glycogen stores so takes 15-20 mins to work
Are there glycogen stores to mobilise?
Danger of rebound hypoglycaemia, as will cause insulin release
What level of glucose defines hypoglycaemia?
How is glucose regulated?
Q1:What occurs first in response to hypoglycaemia?
Suppression of insulin
Investigations?
•Confirm there is hypoglycaemia
•
•Easy in a patient with diabetes
–usually monitor blood glucose (BG)
•Difficult in an otherwise healthy person
–May need to conduct a prolonged fast to demonstrate hypoglycaemia
Glucose measurment?
Lab Glucose
- Grey top (flouride oxalate)
- Venous sample
- 2 mls blood
- Gold std to make the diagnosis
- Delay in results
Blood glucose meter
- Point-of-care device
- Instant result
- Capillary blood
But…
- Poor precision at low glucose levels
- Often poorly maintained
Causes of hypoglycaemia?
Diabetics:
- Commonest cause of hypoglycaemia
- May be related to:
–Medications
–Inadequate CHO intake / missed meal
–Impaired awareness
–Excessive alcohol
–Strenuous exercise
–Co-existing autoimmune conditions
Non Diabetics:
Fasting or reactive?
Paediatric vs. adult
Critically unwell
Organ failure
Hyperinsulinism
Post gastric-bypass
Drugs
Extreme weight loss
Factitious
What are the diabetic medications?
•Oral Hypoglycaemic
–Sulphonylureas
–Meglitinides
–GLP-1 agents
•Insulin
–Rapid acting with meals: inadequate meal
–Long-acting : hypo’s at night or in between meals
•Other drugs
–B-blockers, salicylates, alcohol ( inhibits lipolysis)
How do co morbs affect hyoglycaemia?
- Co-existing renal / liver failure alters drug clearance, and reduced doses needed.
- Rarely concurrent Addison’s can result in hypos (polygladular autoimmune syndrome)
- Caveats:
- Poor awareness can occur due to autonomic neuropathy
- Very serious problem at night, and an indication for continuous glucose monitoring
- A very good HbA1c level in a diabetic, may be due to recurrent hypos.
- End of the honeymoon period
How can we differentiate the cause of hypoglycaemia?
- Thorough history and examination
- Biochemical Tests
–Insulin levels
–C-peptide
–Drug screen
–Auto-antibodies
–Cortisol /GH
–Free fatty acids / blood ketones
–Lactate
–Other specialist tests – IGFBP/IGF-2/Carnitines etc.
What is C peptide?
It is the cleavage product of insulin
C-peptide levels are a good marker of beta-cell function
Also good to help differentiate the cause of hypoglycaemia
C peptide:
Half-life, ~ 30 minutes
Renal Clearance
Insulin:
Half-life, 4-6 minutes
Hepatic clearance
Exogenous insulin may interfere
Hypoglycaemia due to excess injected insulin would result in… (high/ low?) C peptide
low C peptide
20 year old female, BMI 17 kg/m2
Lanugo hair noted
Finger prick glucose – 3.8mmol/L
Routine bloods taken
•Doctor rung by lab 1 hr later as plasma glucose 2.6 mmol/L
What is the most likely cause of her low blood sugar?
poor glycogen liver storage
What would the insulin and C-peptide result be if they had been measured in that patient?
unsure
How does insulin/ c peptide change in different pathologies?
Hypoglycaemia with low insulin + C-peptide?
Appropriate response to hypoglycaemia
Fasting / starvation
Strenuous exercise
Critical illness
Endocrine deficiencies
- Hypopituitarism
- Adrenal failure
Liver failure
Anorexia Nervosa
What is 3-hydroxybutyrate?
A ketone body
What does the absence of ketones signify (glucose 1.9, ketones negative)?
Fatty acid oxidation defect
Neonatal Hypoglycaemia?
Explainable
- Premature, co-morbidities, IUGR, SGA
- Inadequate glycogen and fat stores
- Should improve with feeding
Pathological
•Inborn metabolic defects
Neonatal hypoglycaemia with suppressed insulin + C-peptide?
- FFA raised, but low ketones
- Inherited metabolic disorders
–FAOD : no ketones produced
–GSD type 1 ( gluconeogentic disorder)
–Medium chain acyl coA dehydrogenase def.
–Carnitine disorders
Neonatal hypoglycaemia with suppressed insulin + C-peptide?
Expect high FFA
Expect detectable ketone bodies ( beta hydroxybutyrate, acetoacetate /acetone)
Good differentiators in neonatal hypoglycaemia
- Insulin / C-peptide
- FFA
- KB
- Lactate
- Hepatomegaly
read that again and write it out
What causes inappropriate insulin levels?
- Islet cell tumours – insulinoma
- Drugs; insulin, sulphonylurea
- Islet cell hyperplasia
–Infant of a diabetic mother
–Beckwith Weidemann syndrome
–Nesidioblastosis
45 year old lady admitted fitting. Recurrently seen GP in previous months due to weight gain and increased appetite
Husband reports personality change in last few months.
Glucose 1.9 mmol/L
Insulin 35 mu/L
C-peptide 1000 pmol/L
What is the diagnosis?
Insulinoma or sulfonylurea excess
Low glucose, high insulin and high C-peptide?
Low glucose, high insulin and high C-peptide
- High C-peptide = endogenous insulin production
- Insulinoma vs. Sulphonylurea abuse
- Sulphonylurea drug screen – urine or serum
- Negative sulphonylurea screen required for diagnosing insulinoma
How do sulfonylureas work?
Sulfonylureas bind to and close ATP-sensitive K+ (KATP) (Sur1 subunit) channels on the cell membrane of pancreatic beta cells, which depolarizes the cell by preventing potassium from exiting. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granules with the cell membrane, and therefore increased secretion of mature insulin.
What are Non-islet cell tumour hypoglycaemia?
•Non-islet cell tumour hypoglycaemia
–Tumours that cause a paraneoplastic syndrome
–Secretion of ‘big IGF-2’
–Big IGF2 binds to IGF-1 receptor and insulin receptor
–Mesenchymal tumours ( mesothelioma /fibroblastoma)
–Epithelial tumours ( carcinoma)
What are insulinomas?
–1-2/million/year
–Usually small solitary adenoma
–10% malignant
–8% associated with MEN1
–Diagnosis, based on biochemistry + localisation
–Treatment: resection
9 year old boy brought in fitting.
Glucose 1.9 mmol/L
Insulin 205 mu/L; C-peptide <33 pmol/L
What is the most likely cause of the low blood glucose?
- Glucose consumption during epileptic fit
- Stress response
- Factitious insulin
- Need more information
What is factitous?
Factitious insulin / oral hypoglycaemic usage : always needs to be considered – more common than we think
Suspect in patients with access to insulin / drugs
60 year old cachectic man found unconscious
Smoker
Glucose 1.9 mmol/L
Hypoglycaemia persists – glucose infusion
Insulin and C-peptide undetectable
Free fatty acids – undetectable
Ketones negative
The following diagnosis is likely
???
What are the other causes of this picture:
↓ Glucose ↓ Insulin ↓ C-peptide
↓ FFA ↓ Ketones
Autoimmune conditions: rare
Antibodies to insulin receptors usually present with insulin resistance but rarely hypoglycaemia.
Autoimmune insulin syndrome
Ab’s directed to insulin, sudden dissociation may precipitate hypoglycaemia
Japan
Certain drugs : hydralazine, procainamide etc
What are genetic causes of low glucose?
Glucokinase activating mutation
Congenital hyperinsulinism
- KCNJ11 /ABCC8
- GLUD-1
- HNF4A
- HADH
What are reactive hypos?
- Hypoglycaemia following food intake
- Can occur post-gastric bypass
- Hereditary fructose intolerance
- Early diabetes
- In insulin sensitive individuals after exercise or large meal
- True post-prandial hypo’s
–Difficult to define
- Type 1 diabetic 5 years
- Previously well-controlled
- Now recurrent hypos in morning
Hba1c 6.0 % Noted to be tired ++
Management?
- Review insulin dosing
- Review injection technique
- Consider pump therapy
- Perform a short synacthen test
- All of the above?
