• Plasma hypoglycaemia
• Symptoms attributable to a low blood sugar level
• Resolution of symptoms with correction of the hypoglycaemia

There are many causes of hypoglycaemia, but it is most commonly the result of an excess of either insulin or oral hypoglycaemic medications combined with reduced sugar intake or increased activity. Hypoglycaemia adversely affects quality of life in patients with diabetes.²

Epidemiology

This is a common problem, with diabetes the most common risk factor.

Aetiology

• Alcohol is the most common non-iatrogenic (non physician) cause of hypoglycaemia
• Antidiabetic drugs - especially sulfonylurea overdose:
  • This can lead to profound hypoglycaemia with chlorpropamide and glibenclamide being the agents most frequently implicated.
  • Both prolonged and recurrent hypoglycaemia must be expected. Potassium supplementation is often required.
• Other drugs and toxins including pentamidine, quinine, paracetamol and toadstools
• Rare causes (if insulin and C-peptide levels are elevated, an endogenous insulin source is the cause):
  • Pancreatic endocrine tumour, e.g. insulinoma
  • Extrapancreatic IGF-II secreting neoplasms, e.g. adrenal tumour
  • Autoimmune hypoglycaemia (endogenous antibodies reacting with insulin or the insulin receptors)

Insulinomas

• Insulinomas usually cause semiautonomous release of insulin, resulting in fasting hypoglycaemia.
• In response to meals these tumours usually respond subnormally, so that postprandial glucose levels are normal or even mildly elevated, although postprandial hypoglycaemia can occur.
• Insulinomas may be too small to be seen on CT scans and further investigation with endoscopic ultrasound should be considered, if no other cause for the hypoglycaemia is apparent.
• Glucagon should be used with caution in insulinoma.

Presentation

There is poor correlation between blood glucose and symptoms, especially in diabetic patients.³Patients can often recognise the symptoms themselves and this state responds to sugar in water or a few lumps of sugar. Children may not have such prominent changes but may appear unduly lethargic.
Hypoglycaemia presents as:

• Shaking and trembling
• Sweating, pins and needles in lips and tongue
• Hunger, palpitations
• Headache (occasionally), double vision, difficulty in concentrating
• Slurring of speech, confusion, change of behaviour, truculence
• Stupor, coma

Subacute hypoglycaemia

• Also known as hypoglycaemia unawareness.
  This is seen in insulin-dependent diabetes mellitus (IDDM) patients who may show reduction in spontaneous movements and speech, somnolence, poor thinking and work performance, changes in personality and amnesia. It may also present with transient hemiplegia, hypothermia or hyperthermia, convulsions, diplopia and strabismus.⁴ If untreated, it can progress to stupor, coma and exceptionally death.
• Chronic – a rare presentation with insidious changes in personality, defects in memory, paranoia and apparent dementia. Can also appear as neuropathy mistaken for motor neurone disease.

Management

Adults

• Initially glucose 10-20 g is given by mouth either in liquid form or as granulated sugar or sugar lumps.⁵
• Glucose 10 g is available from 2 teaspoons sugar, 3 sugar lumps, GlucoGel® - formerly known as Hypostop® Gel; glucose 9.2 g/23-g oral ampoule, available from British BioCell International; milk 200 ml; and non-diet versions of Lucozade® Sparkling Glucose Drink 50-55 ml, Coca-Cola® 90 ml, Ribena® Original 15 ml (to be diluted).
• If necessary this may be repeated after 10-15 minutes.

For further management see separate article Emergency Treatment of Hypoglycaemia.

Children

• Prompt treatment of hypoglycaemia in children, from any cause, is essential to prevent subsequent neurological damage.⁶
• Hyperinsulinism, fatty acid oxidation disorders and glycogen storage disease are less common causes of acute hypoglycaemia in children.
• Hypoglycaemia which causes unconsciousness or fitting is an emergency.

Neonates

This is a relatively common problem. Prompt feeding may be all that is required. If, however, this is not possible:

• Neonatal hypoglycaemia is treated with glucose intravenous infusion 10% given at a rate of 5 ml/kg/hour.
• An initial dose of 2.5 ml/kg over 5 minutes may be required if hypoglycaemia is severe enough to cause loss of consciousness or fitting.
• Mild asymptomatic persistent hypoglycaemia may respond to a single dose of glucagon. Dose is 20 mcg per kg.

Glucagon has also been used in the short-term management of endogenous hyperinsulinism.

Chronic hypoglycaemia

Diazoxide, administered by mouth, is useful in the management of children with chronic hypoglycaemia from excess endogenous insulin secretion, either from an islet cell tumour, islet cell hyperplasia or persisting hyperinsulinaemic hypoglycaemia of infancy (nesidioblastosis).

• Diazoxide has no place in the management of acute hypoglycaemia
• Sodium and water retention induced by diazoxide may be reduced by concurrent use of a diuretic
• Chlorothiazide 3-5 mg/kg twice-daily has the added benefit of potentiating the glycaemic effect of diazoxide
• If diazoxide and chlorothiazide fail to suppress excessive glucose requirements then octreotide or nifedipine may be added. There is limited experience for this indication
• Octreotide may suppress growth hormone secretion, but there is little evidence that this has any long-term adverse effect on growth.

Document references

1. Marks V in Oxford Textbook of Medicine, 4th Edition. Eds; Warrell DA et al. OUP 2003.
2. Frier BM; How hypoglycaemia can affect the life of a person with diabetes. Diabetes Metab Res Rev. 2008 Feb;24(2):87-92. [abstract]
3. McAulay V, Deary IJ, Frier BM; Symptoms of hypoglycaemia in people with diabetes.; Diabet Med. 2001 Sep;18(9):690-705. [abstract]
4. Cox D, Gonder-Frederick L, McCall A, et al; The effects of glucose fluctuation on cognitive function and QOL: the functional costs of hypoglycaemia and hyperglycaemia among adults with type 1 or type 2 diabetes.; Int J Clin Pract Suppl. 2002 Jul;(129):20-6. [abstract]
5. Smeeks FC; Hypoglycemia. eMedicine, November 2008.
6. Cranmer H; Pediatrics, hypoglycemia. eMedicine, August 2009.

Internet and further reading

• Hart SP, Frier BM; Causes, management and morbidity of acute hypoglycaemia in adults requiring hospital admission.. QJM. 1998 Jul;91(7):505-10.
• Diabetes (types 1 and 2) - patient education models, NICE Technology Appraisal (2003); The clinical effectiveness and cost effectiveness of patient education models for diabetes.

Acknowledgements