Hypoglycaemia
The most frequent complication of insulin therapy is hypoglycaemia and patients taking insulin need to be educated about its cause, symptoms, and treatment. Most patients can recognise the early warning signs of hypoglycaemia and by taking sugar immediately can prevent more serious symptoms developing. Comatose patients need to be given intravenous glucose or, if this is not practicable, subcutaneous, intramuscular, or intravenous glucagon (although glucose is still required if mere is no response within 10 minutes). Hypoglycaemia can also develop in patients taking oral antidiabetics, notably the sulfonylureas.
Some patients report loss of the warning signs of hypoglycaemia after transferring from animal to human insulin and these patients, if appropriate, may need to be transferred back to animal insulin. However, the most significant factor in loss of hypoglycaemic warning signs may be exposure to hypoglycaemia itself a study found mat total avoidance of hypoglycaemic episodes for 3 weeks while maintaining glycaemic control restored awareness. Loss of hypoglycaemic awareness, which appears to be due to an adaptive conservation of glucose uptake in the brain, is liable to be a particular problem in patients receiving intensive therapy. There is limited data to suggest that caffeine can improve awareness of hypoglycaemia.
Diabetic ketoacidosis
Diabetic ketoacidosis is caused by an absolute or relative lack of insulin and commonly occurs after noncompliance or failure to adjust insulin dosage in the presence of factors such as infection that increase insulin requirements (see Precautions for Insulin). Failure of an insulin pump can be a cause. Also pregnant diabetic women are more prone to development of diabetic ketoacidosis.
Diabetic ketoacidosis is characterised by hyperglycaemia, hyperketonaemia, and acidaemia, with subsequent dehydration and electrolyte abnormalities. Onset may be rapid, or insidious over many days. Initial presenting symptoms such as thirst, polyuria, fatigue, and weight loss are those of any newly presenting type 1 diabetic they then progress to nausea, vomiting, abdominal pain, and impaired consciousness or coma, and, if untreated, death.
Diabetic ketoacidosis is a medical emergency and should be treated immediately with fluid replacement and insulin. Fluid requirements depend on the needs of the individual overvigorous fluid replacement without severe dehydration carries the risk of precipitating cerebral oedema.
Soluble insulin should also be given immediately. Large doses were formerly thought necessary, but lower dose regimens accompanied by adequate hydration have since been shown to be preferable. Insulin resistance in diabetic ketoacidosis is generally exacerbated by hyperosmolarity and other confounding factors, and insulin therapy is therefore most effective when preceded or accompanied by adequate fluid and electrolyte replacement. In the UK, the BNF considers that insulin should preferably be given by intravenous infusion, with the intramuscular route used if facilities for intravenous infusion are not available. However, in the USA some consider that an intravenous bolus followed by subcutaneous injection may be appropriate in certain patients. Intramuscular or subcutaneous injection are not appropriate in patients with hypovolaemic shock, due to poor tissue perfusion. Where the response to insulin is inadequate the intravenous route is generally required and the rate of infusion may be doubled on an hourly basis until an appropriate response is seen. A case report has suggested mat mecasermin may be useful if there is insulin resistance.
When the blood-glucose concentration has fallen to about 12.5 mmol/litre the dose of insulin may be reduced by about half and glucose given intravenously, usually in a strength of 5% with saline although in rare cases a glucose strength of 10% may be necessary. The use of glucose enables insulin to be continued in order to clear ketone bodies without inducing hypoglycaemia. Once glucose concentrations have been controlled and acidosis has completely cleared, subcutaneous injections of insulin can begin but intravenous insulin should not be stopped until subcutaneous dosage has begun.
Total body stores of potassium are depleted in patients with diabetic ketoacidosis. Insulin deficiency appears to be the main initiating factor for hyperkalaemia in diabetic ketoacidosis. Although patients may present with raised, normal, or decreased serum-potassium concentrations, the concentrations will start to fall with the correction of acidosis. Potassium is added to the infusion fluid after initial fluid expansion and once insulin therapy has begun. In hyperkalaemic patients, potassium is given once serum concentrations have fallen to within normal limits. In the rare patient presenting with hypokalaemia potassium replacement should be begun before insulin therapy and the latter withheld until potassium concentrations have risen to normal values.
Intravenous bicarbonate is now generally reserved for patients with severe acidaemia a common practice is to give isotonic bicarbonate to those with a pH of less man 7.0 with the aim of raising the pH to 7.1.
Phosphate concentrations are affected in a similar manner to potassium concentrations in the ketoacidotic state, but there is less agreement on the need for routine doses of phosphate. Phosphate concentrations should be monitored and phosphate given if clinically significant hypophospha-taemia occurs.
The precipitating cause of diabetic ketoacidosis should also be identified and managed appropriately.
Hyperosmolar hyperglycaemic state
Hyperosmolar hyperglycaemic state or hyperosmolar hyperglycaemic nonketotic coma (HONK) occurs mainly in elderly patients with type 2 diabetes and though much
less common man diabetic ketoacidosis it carries a higher mortality. Patients may present in coma with severe hyperglycaemia but with minimal ketosis dehydration and renal impairment are common. Treatment is similar to mat of diabetic ketoacidosis, although potassium requirements are lower and large amounts of fluid and less insulin may be required some suggest the use of hypotonic fluid if necessary. There is an increased likelihood of thrombotic events, so prophylactic anticoagulation should be considered.