Hypoglycaemia

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Hypoglycaemia

Hypoglycaemia is defined as a low blood glucose concentration. In general, children and adults are not usually symptomatic unless the glucose falls below 2.2 mmol/L. Assessment of hypoglycaemia depends critically on the age of the patient, on whether it occurs in the fasting or postprandial state, and on whether the patient has diabetes or not. A detailed drug history is important, and should include over-the-counter and alternative preparations as well as prescribed medications.

Clinical effects

Hypoglycaemia normally leads to suppression of insulin secretion, an increase in catecholamine secretion and stimulation of glucagon, cortisol and growth hormone. The catecholamine surge accounts for the signs and symptoms most commonly seen in hypoglycaemia, i.e. sweating, shaking, tachycardia as well as feeling weak, jittery and nauseated. Hypoglycaemia decreases the glucose fuel supply to the brain and symptoms of cognitive impairment must always be sought since they reflect neuroglycopenia. They include confusion, poor concentration, detachment and, in more severe instances, convulsions and coma. The clinical effects of hypoglycaemia are summarized in Figure 34.1.

Fig 34.1 The clinical effects of hypoglycaemia.

Assessment

The diagnosis of hypoglycaemia is established when three criteria (‘Whipple’s triad’) are satisfied.

There must be symptoms consistent with hypoglycaemia.

There must be laboratory confirmation of hypoglycaemia.

Symptoms must be relieved by the administration of glucose.

As a preliminary step to formal assessment, patients may be supplied with blood spot strips and asked to take fingerprick blood samples during symptomatic episodes. It may be necessary to try to precipitate symptoms, e.g. by prolonged fasting. If a blood sample is being collected for glucose analysis during a symptomatic episode, an additional sample should be collected simultaneously for insulin. This need not be analysed at the time, or indeed at all unless hypoglycaemia is confirmed, but the insulin level critically alters the differential diagnosis of hypoglycaemia (Figs 34.2 and 34.3).

Fig 34.2 The differential diagnosis of hypoglycaemia in the presence of high insulin levels.

Fig 34.3 The differential diagnosis of hypoglycaemia in the absence of high insulin levels.

Specific causes of hypoglycaemia

Causes of hypoglycaemia may be divided into two groups: those which usually produce hypoglycaemia in the fasting patient, and those in which the low glucose is a response to a stimulus (reactive hypoglycaemia).

Fasting hypoglycaemia

Causes of fasting hypoglycaemia include:

Insulinoma. These insulin-producing β-cell tumours of the pancreas may be isolated or part of the wider multiple endocrine neoplasia (MEN) syndrome (see pp. 142–143). Insulin-induced weight gain is a characteristic feature. Localization of the tumour may be difficult.

Malignancy. Hypoglycaemia may be found with any advanced malignancy. Some tumours, e.g. retroperitoneal sarcomas, cause hypoglycaemia by producing insulin-like growth factors.

Hepatic and renal disease. Both the liver and kidneys are capable of gluconeogenesis. Hypoglycaemia is occasionally a feature of advanced hepatic or renal impairment, but this is not usually a diagnostic dilemma.

Addison’s disease. Given the fact that glucocorticoids antagonize the actions of insulin, it should not be surprising that hypoglycaemia is occasionally a feature of adrenal insufficiency.

Sepsis. Overwhelming sepsis may be associated with hypoglycaemia; the mechanism is unclear.

Reactive hypoglycaemia

Insulin-induced. Inappropriate or excessive insulin predictably produces hypoglycaemia. Occasionally it is important to distinguish between exogenous insulin (administered by the patient or someone else) and endogenous insulin. Standard assays for insulin cannot distinguish between the two kinds. However, insulin and its associated connecting peptide (or C-peptide) are secreted by the islet cells in equimolar amounts, and thus measurement of C-peptide along with insulin can differentiate between hypoglycaemia due, for example, to an insulinoma (high C-peptide) and that due to exogenous insulin (low C-peptide) (Fig 34.4).

Fig 34.4 Insulin and C-peptide.

Drug-induced. Oral hypoglycaemics, e.g. sulphonylureas, can produce hypoglycaemia. Urinary screens for sulphonylureas exist. Other drugs that occasionally give rise to hypoglycaemia less predictably include salicylate, paracetamol and β-blockers. More importantly, the last may also mask the patient’s awareness of hypoglycaemia, by blunting the β-effect of adrenaline and reducing or eliminating the warning symptoms such as palpitation or tremor.

Alcohol. Hypoglycaemia is not uncommon in alcoholic patients. Mechanisms include inhibition of gluconeogenesis, malnutrition and liver disease.

‘Dumping syndrome’. Accelerated gastric emptying following gastric resection may result in the rapid absorption of large amounts of glucose with a resultant surge of insulin release. Smaller, more frequent meals may help to minimize this phenomenon.

Diabetic patients

In diabetic patients, hypoglycaemia is rarely a diagnostic dilemma. Precipitating factors include:

insufficient carbohydrate intake

excess of insulin or sulphonylurea

strenuous exercise

excessive alcohol intake.

Neonatal hypoglycaemia

Certain groups of neonates are especially vulnerable to hypoglycaemia:

Small-for-gestational-age infants. Depleted glycogen stores and impaired gluconeogenesis contribute.

Babies of diabetic mothers. A fetus that is exposed to maternal hyperglycaemia will develop hyperplasia of the islet cells and associated hyperinsulinaemia. After delivery, the neonate is unable to suppress its high insulin levels that are now inappropriate, and hypoglycaemia results.

Nesidioblastosis. Hyperplasia of the islet cells may develop even when the mother is not diabetic; the reasons are unclear.

Inborn errors of metabolism. Many inborn errors are associated with hypoglycaemia. Fatty acid oxidation defects, glycogen storage diseases and galactosaemia are important examples.

Clinical note

The use of 50% dextrose as an intravenous bolus has remarkable effects in reversing the signs and symptoms of hypoglycaemia. This solution is like syrup and may cause thrombophlebitis. Care must also be taken not to cause extravasation.

Case history 27

A 25-year-old woman with IDDM complained of repeated episodes of sleep disturbances, night sweats and vivid, unpleasant dreams.

• What is the most likely cause of this woman’s symptoms and how might the diagnosis be confirmed?

Comment on page 166.

Hypoglycaemia

Hypoglycaemia is not a diagnosis but is a biochemical sign associated with a diverse group of diseases.

Management is by glucose therapy irrespective of the underlying cause.

Excess insulin, excess alcohol or low calorie intake in a diabetic patient are the most common causes of hypoglycaemia.

Insulinoma is characterized by hypoglycaemia in the face of inappropriately high plasma insulin.

Hypoglycaemia in the neonate may result in brain damage.

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