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

Hypoglycaemia Flashcards by Can I get Uhhhh?

What is the acute management of hypoglycaemia in alert and oriented adults?

Oral Carbohydrates

Rapid acting; juice / sweets

Longer acting; sandwich

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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

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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

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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

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What level of glucose defines hypoglycaemia?

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How is glucose regulated?

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Q1:What occurs first in response to hypoglycaemia?

Suppression of insulin

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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

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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

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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

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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)

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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

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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.

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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

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Hypoglycaemia due to excess injected insulin would result in… (high/ low?) C peptide

low C peptide

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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?

1. Glucose consumption during epileptic fit 2. Stress response 3. Factitious insulin 4. 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: ## Footnote ↓ 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?

1. Review insulin dosing 2. Review injection technique 3. Consider pump therapy 4. Perform a short synacthen test 5. All of the above?